nach oben

Molecular Diagnosis & Therapy

Erschienen in:

01.04.2014 | Review Article

Biomarker Modelling of Early Molecular Changes in Alzheimer’s Disease

verfasst von: Ross W. Paterson, Jamie Toombs, Catherine F. Slattery, Jonathan M. Schott, Henrik Zetterberg

Erschienen in: Molecular Diagnosis & Therapy | Ausgabe 2/2014

Einloggen, um Zugang zu erhalten

Abstract

The preclinical phase of Alzheimer’s disease (AD) occurs years, possibly decades, before the onset of clinical symptoms. Being able to detect the very earliest stages of AD is critical to improving understanding of AD biology, and identifying individuals at greatest risk of developing clinical symptoms with a view to treating AD pathophysiology before irreversible neurodegeneration occurs. Studies of dominantly inherited AD families and longitudinal studies of sporadic AD have contributed to knowledge of the earliest AD biomarkers. Here we appraise this evidence before reviewing novel, particularly fluid, biomarkers that may provide insights into AD pathogenesis and relate these to existing hypothetical disease models.

Sperling RA, Karlawish J, Johnson KA. Preclinical Alzheimer disease—the challenges ahead. Nat Rev Neurol. 2013;9(1):54–8. doi:10.1038/nrneurol.2012.241.PubMedCentralPubMed

Braak H, Braak E. Evolution of the neuropathology of Alzheimer’s disease. Acta Neurol Scand Suppl. 1996;165:3–12.PubMed

Akiyama H, Arai T, Kondo H, Tanno E, Haga C, Ikeda K. Cell mediators of inflammation in the Alzheimer disease brain. Alzheimer Dis Assoc Disord. 2000;14(Suppl 1):S47–53.PubMed

Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science. 2002;297(5580):353–6. doi:10.1126/science.1072994.PubMed

Perrin RJ, Fagan AM, Holtzman DM. Multimodal techniques for diagnosis and prognosis of Alzheimer’s disease. Nature. 2009;461(7266):916–22. doi:10.1038/nature08538.PubMedCentralPubMed

Zetterberg H, Blennow K. Cerebrospinal fluid biomarkers for Alzheimer’s disease: more to come? J Alzheimers Dis. 2013;33(Suppl 1):S361–9. doi:10.3233/JAD-2012-129035.PubMed

Sperling RA, Jack CR Jr, Aisen PS. Testing the right target and right drug at the right stage. Sci Transl Med. 2011;3(111):111cm33. doi:10.1126/scitranslmed.3002609.PubMedCentralPubMed

Hansson O, Zetterberg H, Buchhave P, Londos E, Blennow K, Minthon L. Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol. 2006;5(3):228–34. doi:10.1016/S1474-4422(06)70355-6.PubMed

Shaw LM, Vanderstichele H, Knapik-Czajka M, Clark CM, Aisen PS, Petersen RC, et al. Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann Neurol. 2009;65(4):403–13. doi:10.1002/ana.21610.PubMedCentralPubMed

10.

Visser PJ, Verhey F, Knol DL, Scheltens P, Wahlund LO, Freund-Levi Y, et al. Prevalence and prognostic value of CSF markers of Alzheimer’s disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study. Lancet Neurol. 2009;8(7):619–27. doi:10.1016/S1474-4422(09)70139-5.PubMed

11.

Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, et al. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA. 2009;302(4):385–93. doi:10.1001/jama.2009.1064.PubMed

12.

Weigand SD, Vemuri P, Wiste HJ, Senjem ML, Pankratz VS, Aisen PS, et al. Transforming cerebrospinal fluid Abeta42 measures into calculated Pittsburgh Compound B units of brain Abeta amyloid. Alzheimers Dement. 2011;7(2):133–41. doi:10.1016/j.jalz.2010.08.230.PubMedCentralPubMed

13.

Olsson A, Vanderstichele H, Andreasen N, De Meyer G, Wallin A, Holmberg B, et al. Simultaneous measurement of beta-amyloid(1-42), total tau, and phosphorylated tau (Thr181) in cerebrospinal fluid by the xMAP technology. Clin Chem. 2005;51(2):336–45. doi:10.1373/clinchem.2004.039347.PubMed

14.

Perret-Liaudet A, Pelpel M, Tholance Y, Dumont B, Vanderstichele H, Zorzi W, et al. Cerebrospinal fluid collection tubes: a critical issue for Alzheimer disease diagnosis. Clin Chem. 2012;58(4):787–9. doi:10.1373/clinchem.2011.178368.PubMed

15.

Toombs J, Paterson RW, Lunn MP, Nicholas JM, Fox NC, Chapman MD et al. Identification of an important potential confound in CSF AD studies: aliquot volume. Clin Chem Lab Med. 2013:1–7. doi:10.1515/cclm-2013-0293.

16.

Bateman RJ, Wen G, Morris JC, Holtzman DM. Fluctuations of CSF amyloid-beta levels: implications for a diagnostic and therapeutic biomarker. Neurology. 2007;68(9):666–9. doi:10.1212/01.wnl.0000256043.50901.e3.PubMed

17.

Schoonenboom NS, Mulder C, Vanderstichele H, Van Elk EJ, Kok A, Van Kamp GJ, et al. Effects of processing and storage conditions on amyloid beta (1-42) and tau concentrations in cerebrospinal fluid: implications for use in clinical practice. Clin Chem. 2005;51(1):189–95. doi:10.1373/clinchem.2004.039735.PubMed

18.

Bjerke M, Portelius E, Minthon L, Wallin A, Anckarsater H, Anckarsater R et al. Confounding factors influencing amyloid beta concentration in cerebrospinal fluid. Int J Alzheimers Dis. 2010;2010. doi:10.4061/2010/986310.

19.

Mattsson N, Andreasson U, Persson S, Arai H, Batish SD, Bernardini S, et al. The Alzheimer’s Association external quality control program for cerebrospinal fluid biomarkers. Alzheimers Dement. 2011;7(4):386.e6–395.e6. doi:10.1016/j.jalz.2011.05.2243.

20.

Mattsson N, Andreasson U, Persson S, Carrillo MC, Collins S, Chalbot S, et al. CSF biomarker variability in the Alzheimer’s Association quality control program. Alzheimers Dement. 2013;9(3):251–61. doi:10.1016/j.jalz.2013.01.010.PubMed

21.

Carrillo MC, Blennow K, Soares H, Lewczuk P, Mattsson N, Oberoi P, et al. Global standardization measurement of cerebral spinal fluid for Alzheimer’s disease: an update from the Alzheimer’s Association Global Biomarkers Consortium. Alzheimers Dement. 2012. doi:10.1016/j.jalz.2012.11.003.PubMedCentral

22.

Bartlett JW, Frost C, Mattsson N, Skillback T, Blennow K, Zetterberg H, et al. Determining cut-points for Alzheimer’s disease biomarkers: statistical issues, methods and challenges. Biomark Med. 2012;6(4):391–400. doi:10.2217/bmm.12.49.PubMed

23.

Fox NC, Scahill RI, Crum WR, Rossor MN. Correlation between rates of brain atrophy and cognitive decline in AD. Neurology. 1999;52(8):1687–9.PubMed

24.

Kaye JA, Swihart T, Howieson D, Dame A, Moore MM, Karnos T, et al. Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia. Neurology. 1997;48(5):1297–304.PubMed

25.

Fox NC, Warrington EK, Rossor MN. Serial magnetic resonance imaging of cerebral atrophy in preclinical Alzheimer’s disease. Lancet. 1999;353(9170):2125.PubMed

26.

Jack CR Jr, Shiung MM, Weigand SD, O’Brien PC, Gunter JL, Boeve BF, et al. Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI. Neurology. 2005;65(8):1227–31.PubMedCentralPubMed

27.

Fox NC, Schott JM. Imaging cerebral atrophy: normal ageing to Alzheimer’s disease. Lancet. 2004;363(9406):392–4. doi:10.1016/S0140-6736(04)15441-X.PubMed

28.

Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade. Lancet Neurol. 2010;9(1):119–28. doi:10.1016/S1474-4422(09)70299-6.PubMedCentralPubMed

29.

Mosconi L, Berti V, Glodzik L, Pupi A, De Santi S, de Leon MJ. Pre-clinical detection of Alzheimer’s disease using FDG-PET, with or without amyloid imaging. J Alzheimers Dis. 2010;20(3):843–54. doi:10.3233/JAD-2010-091504.PubMedCentralPubMed

30.

Rowe CC, Villemagne VL. Brain amyloid imaging. J Nucl Med Technol. 2013;41(1):11–8. doi:10.2967/jnumed.110.076315.PubMed

31.

Leinonen V, Koivisto AM, Savolainen S, Rummukainen J, Tamminen JN, Tillgren T, et al. Amyloid and tau proteins in cortical brain biopsy and Alzheimer’s disease. Ann Neurol. 2010;68(4):446–53. doi:10.1002/ana.22100.PubMed

32.

Seppala TT, Nerg O, Koivisto AM, Rummukainen J, Puli L, Zetterberg H, et al. CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings. Neurology. 2012;78(20):1568–75. doi:10.1212/WNL.0b013e3182563bd0.PubMed

33.

Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, et al. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA. 2011;305(3):275–83. doi:10.1001/jama.2010.2008.PubMed

34.

Ryan NS, Rossor MN. Correlating familial Alzheimer’s disease gene mutations with clinical phenotype. Biomark Med. 2010;4(1):99–112.PubMedCentralPubMed

35.

Fox NC, Warrington EK, Freeborough PA, Hartikainen P, Kennedy AM, Stevens JM, et al. Presymptomatic hippocampal atrophy in Alzheimer’s disease. A longitudinal MRI study. Brain. 1996;119(Pt 6):2001–7.PubMed

36.

Schott JM, Fox NC, Frost C, Scahill RI, Janssen JC, Chan D, et al. Assessing the onset of structural change in familial Alzheimer’s disease. Ann Neurol. 2003;53(2):181–8. doi:10.1002/ana.10424.PubMed

37.

Ridha BH, Barnes J, Bartlett JW, Godbolt A, Pepple T, Rossor MN, et al. Tracking atrophy progression in familial Alzheimer’s disease: a serial MRI study. Lancet Neurol. 2006;5(10):828–34. doi:10.1016/S1474-4422(06)70550-6.PubMed

38.

Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012;367(9):795–804. doi:10.1056/NEJMoa1202753.PubMedCentralPubMed

39.

Knight WD, Okello AA, Ryan NS, Turkheimer FE, Rodriguez Martinez de Llano S, Edison P, et al. Carbon-11-Pittsburgh compound B positron emission tomography imaging of amyloid deposition in presenilin 1 mutation carriers. Brain. 2011;134(Pt 1):293–300. doi:10.1093/brain/awq310.PubMed

40.

Klunk WE, Price JC, Mathis CA, Tsopelas ND, Lopresti BJ, Ziolko SK, et al. Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees. J Neurosci. 2007;27(23):6174–84. doi:10.1523/JNEUROSCI.0730-07.2007.PubMedCentralPubMed

41.

Potter R, Patterson BW, Elbert DL, Ovod V, Kasten T, Sigurdson W, et al. Increased in vivo amyloid-beta42 production, exchange, and loss in presenilin mutation carriers. Sci Transl Med. 2013;5(189):189ra77. doi:10.1126/scitranslmed.3005615.PubMed

42.

Mawuenyega KG, Sigurdson W, Ovod V, Munsell L, Kasten T, Morris JC, et al. Decreased clearance of CNS beta-amyloid in Alzheimer’s disease. Science. 2010;330(6012):1774. doi:10.1126/science.1197623.PubMedCentralPubMed

43.

Reiman EM, Quiroz YT, Fleisher AS, Chen K, Velez-Pardo C, Jimenez-Del-Rio M, et al. Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer’s disease in the presenilin 1 E280A kindred: a case-control study. Lancet Neurol. 2012;11(12):1048–56. doi:10.1016/S1474-4422(12)70228-4.PubMed

44.

Schott JM, Bartlett JW, Fox NC, Barnes J. Increased brain atrophy rates in cognitively normal older adults with low cerebrospinal fluid Abeta1-42. Ann Neurol. 2010;68(6):825–34. doi:10.1002/ana.22315.PubMed

45.

Rowe CC, Ellis KA, Rimajova M, Bourgeat P, Pike KE, Jones G, et al. Amyloid imaging results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. Neurobiol Aging. 2010;31(8):1275–83. doi:10.1016/j.neurobiolaging.2010.04.007.PubMed

46.

Andrews KA, Modat M, Macdonald KE, Yeatman T, Cardoso MJ, Leung KK, et al. Atrophy rates in asymptomatic amyloidosis: implications for Alzheimer prevention trials. PloS One. 2013;8(3):e58816. doi:10.1371/journal.pone.0058816.PubMedCentralPubMed

47.

Mormino EC, Kluth JT, Madison CM, Rabinovici GD, Baker SL, Miller BL, et al. Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. Brain. 2009;132(Pt 5):1310–23. doi:10.1093/brain/awn320.PubMedCentralPubMed

48.

Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol. 2013;12(4):357–67. doi:10.1016/S1474-4422(13)70044-9.PubMed

49.

Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, Aisen PS, et al. Tracking pathophysiological processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12(2):207–16. doi:10.1016/S1474-4422(12)70291-0.PubMedCentralPubMed

50.

Knopman DS, Roberts RO. Healthy young hearts sharper older minds make. Ann Neurol. 2013;73(2):151–2. doi:10.1002/ana.23847.PubMedCentralPubMed

51.

Chetelat G. Alzheimer disease: Abeta-independent processes-rethinking preclinical AD. Nat Rev Neurol. 2013;9(3):123–4. doi:10.1038/nrneurol.2013.21.PubMedCentralPubMed

52.

Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6(8):734–46. doi:10.1016/S1474-4422(07)70178-3.PubMed

53.

McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263–9. doi:10.1016/j.jalz.2011.03.005.PubMedCentralPubMed

54.

Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):270–9. doi:10.1016/j.jalz.2011.03.008.PubMedCentralPubMed

55.

Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):280–92. doi:10.1016/j.jalz.2011.03.003.PubMedCentralPubMed

56.

Lam B, Masellis M, Freedman M, Stuss DT, Black SE. Clinical, imaging, and pathological heterogeneity of the Alzheimer’s disease syndrome. Alzheimers Res Ther. 2013;5(1):1. doi:10.1186/alzrt155.PubMedCentralPubMed

57.

Genin E, Hannequin D, Wallon D, Sleegers K, Hiltunen M, Combarros O, et al. APOE and Alzheimer disease: a major gene with semi-dominant inheritance. Mol Psychiatry. 2011;16(9):903–7. doi:10.1038/mp.2011.52.PubMedCentralPubMed

58.

Prince JA, Zetterberg H, Andreasen N, Marcusson J, Blennow K. APOE epsilon4 allele is associated with reduced cerebrospinal fluid levels of Abeta42. Neurology. 2004;62(11):2116–8.PubMed

59.

Andreasson U, Lautner R, Schott JM, Mattsson N, Hansson O, Herukka SK, et al. CSF biomarkers for Alzheimer’s pathology and the effect size of APOE varepsilon4. Mol Psychiatry. 2013. doi:10.1038/mp.2013.18.PubMedCentralPubMed

60.

Sheline YI, Morris JC, Snyder AZ, Price JL, Yan Z, D’Angelo G, et al. APOE4 allele disrupts resting state fMRI connectivity in the absence of amyloid plaques or decreased CSF Abeta42. J Neurosci. 2010;30(50):17035–40. doi:10.1523/JNEUROSCI.3987-10.2010.PubMedCentralPubMed

61.

Scarmeas N, Habeck CG, Stern Y, Anderson KE. APOE genotype and cerebral blood flow in healthy young individuals. JAMA. 2003;290(12):1581–2. doi:10.1001/jama.290.12.1581.PubMedCentralPubMed

62.

Naj AC, Jun G, Beecham GW, Wang LS, Vardarajan BN, Buros J, et al. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet. 2011;43(5):436–41. doi:10.1038/ng.801.PubMedCentralPubMed

63.

Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, et al. TREM2 variants in Alzheimer’s disease. N Engl J Med. 2013;368(2):117–27. doi:10.1056/NEJMoa1211851.PubMedCentralPubMed

64.

Fagan AM, Perrin RJ. Upcoming candidate cerebrospinal fluid biomarkers of Alzheimer’s disease. Biomark Med. 2012;6(4):455–76. doi:10.2217/bmm.12.42.PubMedCentralPubMed

65.

Lo JT. Functional model of biological neural networks. Cogn Neurodyn. 2010;4(4):295–313. doi:10.1007/s11571-010-9110-4.PubMedCentralPubMed

66.

Zhang Y, Schuff N, Du AT, Rosen HJ, Kramer JH, Gorno-Tempini ML, et al. White matter damage in frontotemporal dementia and Alzheimer’s disease measured by diffusion MRI. Brain. 2009;132(Pt 9):2579–92. doi:10.1093/brain/awp071.PubMedCentralPubMed

67.

Gusnard DA, Raichle ME, Raichle ME. Searching for a baseline: functional imaging and the resting human brain. Nat Rev Neurosci. 2001;2(10):685–94.PubMed

68.

Buckner RL, Snyder AZ, Shannon BJ, LaRossa G, Sachs R, Fotenos AF, et al. Molecular, structural, and functional characterization of Alzheimer’s disease: evidence for a relationship between default activity, amyloid, and memory. J Neurosci. 2005;25(34):7709–17. doi:10.1523/JNEUROSCI.2177-05.2005.PubMed

69.

Buckner RL, Sepulcre J, Talukdar T, Krienen FM, Liu H, Hedden T, et al. Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer’s disease. J Neurosci. 2009;29(6):1860–73.PubMedCentralPubMed

70.

Lehmann M, Koedam EL, Barnes J, Bartlett JW, Barkhof F, Wattjes MP, et al. Visual ratings of atrophy in MCI: prediction of conversion and relationship with CSF biomarkers. Neurobiol Aging. 2013;34(1):73–82. doi:10.1016/j.neurobiolaging.2012.03.010.PubMed

71.

Sorg C, Riedl V, Muhlau M, Calhoun VD, Eichele T, Laer L, et al. Selective changes of resting-state networks in individuals at risk for Alzheimer’s disease. Proc Natl Acad Sci USA. 2007;104(47):18760–5. doi:10.1073/pnas.0708803104.PubMedCentralPubMed

72.

Petrella JR, Sheldon FC, Prince SE, Calhoun VD, Doraiswamy PM. Default mode network connectivity in stable vs progressive mild cognitive impairment. Neurology. 2011;76(6):511–7.PubMedCentralPubMed

73.

Zhou J, Greicius MD, Gennatas ED, Growdon ME, Jang JY, Rabinovici GD, et al. Divergent network connectivity changes in behavioural variant frontotemporal dementia and Alzheimer’s disease. Brain. 2010;133(Pt 5):1352–67. doi:10.1093/brain/awq075.PubMedCentralPubMed

74.

Warren JD, Rohrer JD, Schott JM, Fox NC, Hardy J, Rossor MN. Molecular nexopathies: a new paradigm of neurodegenerative disease. Trends Neurosci. 2013. doi:10.1016/j.tins.2013.06.007.PubMedCentralPubMed

75.

Maruyama M, Shimada H, Suhara T, Shinotoh H, Ji B, Maeda J, et al. Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron. 2013;79(6):1094–108. doi:10.1016/j.neuron.2013.07.037.PubMed

76.

Zhang W, Arteaga J, Cashion DK, Chen G, Gangadharmath U, Gomez LF, et al. A highly selective and specific PET tracer for imaging of tau pathologies. J Alzheimers Dis. 2012;31(3):601–12. doi:10.3233/JAD-2012-120712.PubMed

77.

Chien DT, Bahri S, Szardenings AK, Walsh JC, Mu F, Su MY, et al. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J Alzheimers Dis. 2013;34(2):457–68. doi:10.3233/JAD-122059.PubMed

78.

Okamura N, Furumoto S, Harada R, Tago T, Yoshikawa T, Fodero-Tavoletti M, et al. Novel 18F-labeled arylquinoline derivatives for noninvasive imaging of tau pathology in Alzheimer disease. J Nucl Med. 2013;54(8):1420–7. doi:10.2967/jnumed.112.117341.PubMed

79.

Nalivaeva NN, Turner AJ. The amyloid precursor protein: a biochemical enigma in brain development, function and disease. FEBS Lett. 2013;587(13):2046–54. doi:10.1016/j.febslet.2013.05.010.PubMed

80.

Abramsson A, Kettunen P, Banote RK, Lott E, Li M, Arner A, et al. The zebrafish amyloid precursor protein-b is required for motor neuron guidance and synapse formation. Dev Biol. 2013;381(2):377–88. doi:10.1016/j.ydbio.2013.06.026.PubMed

81.

Octave JN, Pierrot N, Ferao Santos S, Nalivaeva NN, Turner AJ. From synaptic spines to nuclear signaling: nuclear and synaptic actions of the amyloid precursor protein. J Neurochem. 2013;126(2):183–90. doi:10.1111/jnc.12239.PubMed

82.

Lei P, Ayton S, Finkelstein DI, Spoerri L, Ciccotosto GD, Wright DK, et al. Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nat Med. 2012;18(2):291–5. doi:10.1038/nm.2613.PubMed

83.

Borroni B, Pilotto A, Bonvicini C, Archetti S, Alberici A, Lupi A, et al. Atypical presentation of a novel Presenilin 1 R377W mutation: sporadic, late-onset Alzheimer disease with epilepsy and frontotemporal atrophy. Neurol Sci. 2012;33(2):375–8. doi:10.1007/s10072-011-0714-1.PubMed

84.

Zainaghi IA, Talib LL, Diniz BS, Gattaz WF, Forlenza OV. Reduced platelet amyloid precursor protein ratio (APP ratio) predicts conversion from mild cognitive impairment to Alzheimer’s disease. J Neural Transm. 2012;119(7):815–9. doi:10.1007/s00702-012-0807-x.PubMed

85.

Srisawat C, Junnu S, Peerapittayamongkol C, Futrakul A, Soi-ampornkul R, Senanarong V, et al. The platelet amyloid precursor protein ratio as a diagnostic marker for Alzheimer’s disease in Thai patients. J Clin Neurosci. 2013;20(5):644–8. doi:10.1016/j.jocn.2012.06.008.PubMed

86.

Jelic V, Hagman G, Yamamoto NG, Teranishi Y, Nishimura T, Winblad B, et al. Abnormal platelet amyloid-beta protein precursor (AbetaPP) metabolism in Alzheimer’s disease: identification and characterization of a new AbetaPP isoform as potential biomarker. J Alzheimers Dis. 2013;35(2):285–95. doi:10.3233/JAD-122122.PubMed

87.

Grimmer T, Wutz C, Drzezga A, Forster S, Forstl H, Ortner M, et al. The usefulness of amyloid imaging in predicting the clinical outcome after two years in subjects with mild cognitive impairment. Curr Alzheimer Res. 2013;10(1):82–5.PubMed

88.

Mattsson N, Ruetschi U, Pijnenburg YA, Blankenstein MA, Podust VN, Li S, et al. Novel cerebrospinal fluid biomarkers of axonal degeneration in frontotemporal dementia. Mol Med Rep. 2008;1(5):757–61. doi:10.3892/mmr_00000025.PubMed

89.

Tesco G, Koh YH, Kang EL, Cameron AN, Das S, Sena-Esteves M, et al. Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity. Neuron. 2007;54(5):721–37. doi:10.1016/j.neuron.2007.05.012.PubMedCentralPubMed

90.

Holsinger RM, McLean CA, Collins SJ, Masters CL, Evin G. Increased beta-secretase activity in cerebrospinal fluid of Alzheimer’s disease subjects. Ann Neurol. 2004;55(6):898–9. doi:10.1002/ana.20144.PubMed

91.

Barao S, Zhou L, Adamczuk K, Vanhoutvin T, Leuven F, Demedts D, et al. BACE1 levels correlate with phospho-tau levels in human cerebrospinal fluid. Curr Alzheimer Res. 2013;10(7):671–8.PubMed

92.

Mattsson N, Rajendran L, Zetterberg H, Gustavsson M, Andreasson U, Olsson M, et al. BACE1 inhibition induces a specific cerebrospinal fluid beta-amyloid pattern that identifies drug effects in the central nervous system. PloS One. 2012;7(2):e31084. doi:10.1371/journal.pone.0031084.PubMedCentralPubMed

93.

Pera M, Alcolea D, Sanchez-Valle R, Guardia-Laguarta C, Colom-Cadena M, Badiola N, et al. Distinct patterns of APP processing in the CNS in autosomal-dominant and sporadic Alzheimer disease. Acta Neuropathol. 2013;125(2):201–13. doi:10.1007/s00401-012-1062-9.PubMedCentralPubMed

94.

Bibl M, Esselmann H, Wiltfang J. Neurochemical biomarkers in Alzheimer’s disease and related disorders. Ther Adv Neurol Disord. 2012;5(6):335–48. doi:10.1177/1756285612455367.PubMedCentralPubMed

95.

Sjögren M, Davidsson P, Gottfries J, Vanderstichele H, Edman A, Vanmechelen E, et al. The cerebrospinal fluid levels of tau, growth-associated protein-43 and soluble amyloid precursor protein correlate in Alzheimer’s disease, reflecting a common pathophysiological process. Dement Geriatr Cogn Disord. 2001;12(4):257–64. doi:10.1159/000051268.PubMed

96.

Lewczuk P, Kornhuber J, Vanmechelen E, Peters O, Heuser I, Maier W, et al. Amyloid beta peptides in plasma in early diagnosis of Alzheimer’s disease: a multicenter study with multiplexing. Exp Neurol. 2010;223(2):366–70. doi:10.1016/j.expneurol.2009.07.024.PubMed

97.

Rosen C, Andreasson U, Mattsson N, Marcusson J, Minthon L, Andreasen N, et al. Cerebrospinal fluid profiles of amyloid beta-related biomarkers in Alzheimer’s disease. Neuromol Med. 2012;14(1):65–73. doi:10.1007/s12017-012-8171-4.

98.

Brinkmalm G, Brinkmalm A, Bourgeois P, Persson R, Hansson O, Portelius E, et al. Soluble amyloid precursor protein alpha and beta in CSF in Alzheimer’s disease. Brain Res. 2013;1513:117–26. doi:10.1016/j.brainres.2013.03.019.PubMed

99.

Alexopoulos P, Guo LH, Jiang M, Bujo H, Grimmer T, Forster S, et al. Amyloid cascade and tau pathology cerebrospinal fluid markers in mild cognitive impairment with regards to Alzheimer’s disease cerebral metabolic signature. J Alzheimers Dis. 2013;36(2):401–8. doi:10.3233/JAD-122329.PubMed

100.

Perneczky R, Guo LH, Kagerbauer SM, Werle L, Kurz A, Martin J, et al. Soluble amyloid precursor protein beta as blood-based biomarker of Alzheimer’s disease. Transl Psychiatry. 2013;3:e227. doi:10.1038/tp.2013.11.PubMedCentralPubMed

101.

Wu G, Sankaranarayanan S, Wong J, Tugusheva K, Michener MS, Shi X, et al. Characterization of plasma beta-secretase (BACE1) activity and soluble amyloid precursor proteins as potential biomarkers for Alzheimer’s disease. J Neurosci Res. 2012;90(12):2247–58. doi:10.1002/jnr.23122.PubMed

102.

Walsh ST, Kossiakoff AA. Crystal structure and site 1 binding energetics of human placental lactogen. J Mol Biol. 2006;358(3):773–84. doi:10.1016/j.jmb.2006.02.038.PubMed

103.

Young-Collier KJ, McArdle M, Bennett JP. The dying of the light: mitochondrial failure in Alzheimer’s disease. J Alzheimers Dis. 2012;28(4):771–81. doi:10.3233/JAD-2011-111487.PubMed

104.

Barghorn S, Nimmrich V, Striebinger A, Krantz C, Keller P, Janson B, et al. Globular amyloid beta-peptide oligomer—a homogenous and stable neuropathological protein in Alzheimer’s disease. J Neurochem. 2005;95(3):834–47. doi:10.1111/j.1471-4159.2005.03407.x.PubMed

105.

Esparza TJ, Zhao H, Cirrito JR, Cairns NJ, Bateman RJ, Holtzman DM, et al. Amyloid-beta oligomerization in Alzheimer dementia versus high-pathology controls. Ann Neurol. 2013;73(1):104–19. doi:10.1002/ana.23748.PubMedCentralPubMed

106.

Stenh C, Englund H, Lord A, Johansson AS, Almeida CG, Gellerfors P, et al. Amyloid-beta oligomers are inefficiently measured by enzyme-linked immunosorbent assay. Ann Neurol. 2005;58(1):147–50. doi:10.1002/ana.20524.PubMed

107.

Georganopoulou DG, Chang L, Nam JM, Thaxton CS, Mufson EJ, Klein WL, et al. Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer’s disease. Proc Natl Acad Sci USA. 2005;102(7):2273–6. doi:10.1073/pnas.0409336102.PubMedCentralPubMed

108.

Santos AN, Torkler S, Nowak D, Schlittig C, Goerdes M, Lauber T, et al. Detection of amyloid-beta oligomers in human cerebrospinal fluid by flow cytometry and fluorescence resonance energy transfer. J Alzheimers Dis. 2007;11(1):117–25.PubMed

109.

Gatson JW, Warren V, Abdelfattah K, Wolf S, Hynan LS, Moore C, et al. Detection of beta-amyloid oligomers as a predictor of neurological outcome after brain injury. J Neurosurg. 2013;118(6):1336–42. doi:10.3171/2013.2.JNS121771.PubMed

110.

Nimmrich V, Grimm C, Draguhn A, Barghorn S, Lehmann A, Schoemaker H, et al. Amyloid beta oligomers (A beta(1-42) globulomer) suppress spontaneous synaptic activity by inhibition of P/Q-type calcium currents. J Neurosci. 2008;28(4):788–97. doi:10.1523/JNEUROSCI.4771-07.2008.PubMed

111.

Holtta M, Hansson O, Andreasson U, Hertze J, Minthon L, Nagga K, et al. Evaluating amyloid-beta oligomers in cerebrospinal fluid as a biomarker for Alzheimer’s disease. PloS One. 2013;8(6):e66381. doi:10.1371/journal.pone.0066381.PubMedCentralPubMed

112.

Iwatsubo T, Mann DM, Odaka A, Suzuki N, Ihara Y. Amyloid beta protein (A beta) deposition: A beta 42(43) precedes A beta 40 in Down syndrome. Ann Neurol. 1995;37(3):294–9. doi:10.1002/ana.410370305.PubMed

113.

Fei M, Jianghua W, Rujuan M, Wei Z, Qian W. The relationship of plasma Abeta levels to dementia in aging individuals with mild cognitive impairment. J Neurol Sci. 2011;305(1–2):92–6. doi:10.1016/j.jns.2011.03.005.PubMed

114.

Seppala TT, Herukka SK, Hanninen T, Tervo S, Hallikainen M, Soininen H, et al. Plasma Abeta42 and Abeta40 as markers of cognitive change in follow-up: a prospective, longitudinal, population-based cohort study. J Neurol Neurosurg Psychiatry. 2010;81(10):1123–7. doi:10.1136/jnnp.2010.205757.PubMedCentralPubMed

115.

Graff-Radford NR, Crook JE, Lucas J, Boeve BF, Knopman DS, Ivnik RJ, et al. Association of low plasma Abeta42/Abeta40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease. Arch Neurol. 2007;64(3):354–62. doi:10.1001/archneur.64.3.354.PubMed

116.

Figurski MJ, Waligorska T, Toledo J, Vanderstichele H, Korecka M, Lee VM, et al. Improved protocol for measurement of plasma beta-amyloid in longitudinal evaluation of Alzheimer’s Disease Neuroimaging Initiative study patients. Alzheimers Dement. 2012;8(4):250–60. doi:10.1016/j.jalz.2012.01.001.PubMedCentralPubMed

117.

Schott JM, Revesz T. Inflammation in Alzheimer’s disease: insights from immunotherapy. Brain. 2013;136(Pt 9):2654–6. doi:10.1093/brain/awt231.PubMed

118.

Colasanti T, Barbati C, Rosano G, Malorni W, Ortona E. Autoantibodies in patients with Alzheimer’s disease: pathogenetic role and potential use as biomarkers of disease progression. Autoimmun Rev. 2010;9(12):807–11. doi:10.1016/j.autrev.2010.07.008.PubMed

119.

Nath A, Hall E, Tuzova M, Dobbs M, Jons M, Anderson C, et al. Autoantibodies to amyloid beta-peptide (Abeta) are increased in Alzheimer’s disease patients and Abeta antibodies can enhance Abeta neurotoxicity: implications for disease pathogenesis and vaccine development. Neuromol Med. 2003;3(1):29–39.

120.

Du Y, Dodel R, Hampel H, Buerger K, Lin S, Eastwood B, et al. Reduced levels of amyloid beta-peptide antibody in Alzheimer disease. Neurology. 2001;57(5):801–5.PubMed

121.

Henkel AW, Dittrich PS, Groemer TW, Lemke EA, Klingauf J, Klafki HW, et al. Immune complexes of auto-antibodies against A beta 1-42 peptides patrol cerebrospinal fluid of non-Alzheimer’s patients. Mol Psychiatry. 2007;12(6):601–10. doi:10.1038/sj.mp.4001947.PubMed

122.

Hyman BT, Smith C, Buldyrev I, Whelan C, Brown H, Tang MX, et al. Autoantibodies to amyloid-beta and Alzheimer’s disease. Ann Neurol. 2001;49(6):808–10.PubMed

123.

Britschgi M, Olin CE, Johns HT, Takeda-Uchimura Y, LeMieux MC, Rufibach K, et al. Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer’s disease. Proc Natl Acad Sci USA. 2009;106(29):12145–50. doi:10.1073/pnas.0904866106.PubMedCentralPubMed

124.

Zotova E, Bharambe V, Cheaveau M, Morgan W, Holmes C, Harris S, et al. Inflammatory components in human Alzheimer’s disease and after active amyloid-beta42 immunization. Brain. 2013;136(Pt 9):2677–96. doi:10.1093/brain/awt210.PubMed

125.

Gustafsen C, Glerup S, Pallesen LT, Olsen D, Andersen OM, Nykjaer A, et al. Sortilin and SorLA display distinct roles in processing and trafficking of amyloid precursor protein. J Neurosci. 2013;33(1):64–71. doi:10.1523/JNEUROSCI.2371-12.2013.PubMed

126.

Willnow TE, Andersen OM. Sorting receptor SORLA—a trafficking path to avoid Alzheimer disease. J Cell Sci. 2013;126(Pt 13):2751–60. doi:10.1242/jcs.125393.PubMed

127.

Schmidt V, Baum K, Lao A, Rateitschak K, Schmitz Y, Teichmann A, et al. Quantitative modelling of amyloidogenic processing and its influence by SORLA in Alzheimer’s disease. EMBO J. 2012;31(1):187–200. doi:10.1038/emboj.2011.352.PubMedCentralPubMed

128.

Scherzer CR, Offe K, Gearing M, Rees HD, Fang G, Heilman CJ, et al. Loss of apolipoprotein E receptor LR11 in Alzheimer disease. Arch Neurol. 2004;61(8):1200–5. doi:10.1001/archneur.61.8.1200.PubMed

129.

Dodson SE, Gearing M, Lippa CF, Montine TJ, Levey AI, Lah JJ. LR11/SorLA expression is reduced in sporadic Alzheimer disease but not in familial Alzheimer disease. J Neuropathol Exp Neurol. 2006;65(9):866–72. doi:10.1097/01.jnen.0000228205.19915.20.PubMedCentralPubMed

130.

Alexopoulos P, Guo LH, Tsolakidou A, Kratzer M, Grimmer T, Westerteicher C, et al. Interrelations between CSF soluble AbetaPPbeta, amyloid-beta 1-42, SORL1, and tau levels in Alzheimer’s disease. J Alzheimers Dis. 2012;28(3):543–52. doi:10.3233/JAD-2011-110983.PubMed

131.

Tsolakidou A, Alexopoulos P, Guo LH, Grimmer T, Westerteicher C, Kratzer M, et al. Beta-site amyloid precursor protein-cleaving enzyme 1 activity is related to cerebrospinal fluid concentrations of sortilin-related receptor with A-type repeats, soluble amyloid precursor protein, and tau. Alzheimers Dement. 2013;9(4):386–91. doi:10.1016/j.jalz.2012.01.015.PubMed

132.

Dinkel PD, Siddiqua A, Huynh H, Shah M, Margittai M. Variations in filament conformation dictate seeding barrier between three- and four-repeat tau. Biochemistry. 2011;50(20):4330–6. doi:10.1021/bi2004685.PubMed

133.

Brys M, Pirraglia E, Rich K, Rolstad S, Mosconi L, Switalski R, et al. Prediction and longitudinal study of CSF biomarkers in mild cognitive impairment. Neurobiol Aging. 2009;30(5):682–90. doi:10.1016/j.neurobiolaging.2007.08.010.PubMedCentralPubMed

134.

Buee L, Bussiere T, Buee-Scherrer V, Delacourte A, Hof PR. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Rev. 2000;33(1):95–130.PubMed

135.

Billingsley ML, Kincaid RL. Regulated phosphorylation and dephosphorylation of tau protein: effects on microtubule interaction, intracellular trafficking and neurodegeneration. Biochem J. 1997;323(Pt 3):577–91.PubMedCentralPubMed

136.

Uchihara T, Hara M, Nakamura A, Hirokawa K. Tangle evolution linked to differential 3- and 4-repeat tau isoform deposition: a double immunofluorolabeling study using two monoclonal antibodies. Histochem Cell Biol. 2012;137(2):261–7. doi:10.1007/s00418-011-0891-2.PubMed

137.

Clavaguera F, Lavenir I, Falcon B, Frank S, Goedert M, Tolnay M. “Prion-like” templated misfolding in tauopathies. Brain Pathol. 2013;23(3):342–9. doi:10.1111/bpa.12044.PubMed

138.

Gile GH, Faktorova D, Castlejohn CA, Burger G, Lang BF, Farmer MA, et al. Distribution and phylogeny of EFL and EF-1alpha in Euglenozoa suggest ancestral co-occurrence followed by differential loss. PloS One. 2009;4(4):e5162. doi:10.1371/journal.pone.0005162.PubMedCentralPubMed

139.

Luk C, Compta Y, Magdalinou N, Marti MJ, Hondhamuni G, Zetterberg H, et al. Development and assessment of sensitive immuno-PCR assays for the quantification of cerebrospinal fluid three- and four-repeat tau isoforms in tauopathies. J Neurochem. 2012;123(3):396–405. doi:10.1111/j.1471-4159.2012.07911.x.PubMed

140.

Yang FM, Grigorenko A, Tommet D, Farias ST, Mungas D, Bennett DA, et al. AD pathology and cerebral infarctions are associated with memory and executive functioning one and five years before death. J Clin Exp Neuropsychol. 2012. doi:10.1080/13803395.2012.740001.PubMedCentralPubMed

141.

Lee JM, Blennow K, Andreasen N, Laterza O, Modur V, Olander J, et al. The brain injury biomarker VLP-1 is increased in the cerebrospinal fluid of Alzheimer disease patients. Clin Chem. 2008;54(10):1617–23. doi:10.1373/clinchem.2008.104497.PubMedCentralPubMed

142.

Tarawneh R, D’Angelo G, Macy E, Xiong C, Carter D, Cairns NJ, et al. Visinin-like protein-1: diagnostic and prognostic biomarker in Alzheimer disease. Ann Neurol. 2011;70(2):274–85. doi:10.1002/ana.22448.PubMedCentralPubMed

143.

Luo X, Hou L, Shi H, Zhong X, Zhang Y, Zheng D, et al. CSF levels of the neuronal injury biomarker visinin-like protein-1 in Alzheimer’s disease and dementia with Lewy bodies. J Neurochem. 2013. doi:10.1111/jnc.12331.

144.

Braunewell KH. The visinin-like proteins VILIP-1 and VILIP-3 in Alzheimer’s disease-old wine in new bottles. Front Mol Neurosci. 2012;5:20. doi:10.3389/fnmol.2012.00020.PubMedCentralPubMed

145.

Masliah E, Mallory M, Alford M, DeTeresa R, Hansen LA, McKeel DW Jr, et al. Altered expression of synaptic proteins occurs early during progression of Alzheimer’s disease. Neurology. 2001;56(1):127–9.PubMed

146.

Bogdanovic N, Davidsson P, Volkmann I, Winblad B, Blennow K. Growth-associated protein GAP-43 in the frontal cortex and in the hippocampus in Alzheimer’s disease: an immunohistochemical and quantitative study. J Neural Transm. 2000;107(4):463–78.PubMed

147.

Milne GL, Musiek ES, Morrow JD. F2-isoprostanes as markers of oxidative stress in vivo: an overview. Biomarkers. 2005;10(Suppl 1):S10–23. doi:10.1080/13547500500216546.PubMed

148.

Il’yasova D, Morrow JD, Ivanova A, Wagenknecht LE. Epidemiological marker for oxidant status: comparison of the ELISA and the gas chromatography/mass spectrometry assay for urine 2,3-dinor-5,6-dihydro-15-F2t-isoprostane. Ann Epidemiol. 2004;14(10):793–7. doi:10.1016/j.annepidem.2004.03.003.PubMed

149.

Janicka M, Kot-Wasik A, Kot J, Namiesnik J. Isoprostanes-biomarkers of lipid peroxidation: their utility in evaluating oxidative stress and analysis. Int J Mol Sci. 2010;11(11):4631–59. doi:10.3390/ijms11114631.PubMedCentralPubMed

150.

Yan W, Byrd GD, Ogden MW. Quantitation of isoprostane isomers in human urine from smokers and nonsmokers by LC-MS/MS. J Lipid Res. 2007;48(7):1607–17. doi:10.1194/jlr.M700097-JLR200.PubMed

151.

Klawitter J, Haschke M, Shokati T, Klawitter J, Christians U. Quantification of 15-F2t-isoprostane in human plasma and urine: results from enzyme-linked immunoassay and liquid chromatography/tandem mass spectrometry cannot be compared. Rapid Commun Mass Spectrom. 2011;25(4):463–8. doi:10.1002/rcm.4871.PubMed

152.

Tsikas D, Suchy MT. Assessment of urinary F(2)-isoprostanes in experimental and clinical studies: mass spectrometry versus ELISA. Hypertension. 2012;60(2):e14; author reply e5. doi:10.1161/HYPERTENSIONAHA.112.199315.

153.

Montine TJ, Kaye JA, Montine KS, McFarland L, Morrow JD, Quinn JF. Cerebrospinal fluid abeta42, tau, and f2-isoprostane concentrations in patients with Alzheimer disease, other dementias, and in age-matched controls. Arch Pathol Lab Med. 2001;125(4):510–2. doi:10.1043/0003-9985(2001)125<0510:CFATAF>2.0.CO;2.PubMed

154.

Mosconi L, Glodzik L, Mistur R, McHugh P, Rich KE, Javier E, et al. Oxidative stress and amyloid-beta pathology in normal individuals with a maternal history of Alzheimer’s. Biol Psychiatry. 2010;68(10):913–21. doi:10.1016/j.biopsych.2010.07.011.PubMedCentralPubMed

155.

Duits FH, Kester MI, Scheffer PG, Blankenstein MA, Scheltens P, Teunissen CE, et al. Increase in cerebrospinal fluid F2-isoprostanes is related to cognitive decline in APOE epsilon4 carriers. J Alzheimers Dis. 2013;36(3):563–70. doi:10.3233/JAD-122227.PubMed

156.

Kester MI, Scheffer PG, Koel-Simmelink MJ, Twaalfhoven H, Verwey NA, Veerhuis R, et al. Serial CSF sampling in Alzheimer’s disease: specific versus non-specific markers. Neurobiol Aging. 2012;33(8):1591–8. doi:10.1016/j.neurobiolaging.2011.05.013.PubMed

157.

Montine TJ, Quinn JF, Milatovic D, Silbert LC, Dang T, Sanchez S, et al. Peripheral F2-isoprostanes and F4-neuroprostanes are not increased in Alzheimer’s disease. Ann Neurol. 2002;52(2):175–9. doi:10.1002/ana.10272.PubMed

158.

Sarma JV, Ward PA. The complement system. Cell Tissue Res. 2011;343(1):227–35. doi:10.1007/s00441-010-1034-0.PubMedCentralPubMed

159.

Lambert JC, Heath S, Even G, Campion D, Sleegers K, Hiltunen M, et al. Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer’s disease. Nat Genet. 2009;41(10):1094–9. doi:10.1038/ng.439.PubMed

160.

Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A, Hamshere ML, et al. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat Genet. 2009;41(10):1088–93. doi:10.1038/ng.440.PubMedCentralPubMed

161.

Seshadri S, Fitzpatrick AL, Ikram MA, DeStefano AL, Gudnason V, Boada M, et al. Genome-wide analysis of genetic loci associated with Alzheimer disease. JAMA. 2010;303(18):1832–40. doi:10.1001/jama.2010.574.PubMedCentralPubMed

162.

Hollingworth P, Harold D, Sims R, Gerrish A, Lambert JC, Carrasquillo MM, et al. Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet. 2011;43(5):429–35. doi:10.1038/ng.803.PubMedCentralPubMed

163.

Eikelenboom P, Hack CE, Kamphorst W, Rozemuller JM. Distribution pattern and functional state of complement proteins and alpha 1-antichymotrypsin in cerebral beta/A4 deposits in Alzheimer’s disease. Res Immunol. 1992;143(6):617–20.PubMed

164.

Crehan H, Holton P, Wray S, Pocock J, Guerreiro R, Hardy J. Complement receptor 1 (CR1) and Alzheimer’s disease. Immunobiology. 2012;217(2):244–50. doi:10.1016/j.imbio.2011.07.017.PubMed

165.

Daborg J, Andreasson U, Pekna M, Lautner R, Hanse E, Minthon L, et al. Cerebrospinal fluid levels of complement proteins C3, C4 and CR1 in Alzheimer’s disease. J Neural Transm. 2012;119(7):789–97. doi:10.1007/s00702-012-0797-8.PubMed

166.

DeKosky ST, Ikonomovic MD, Wang X, Farlow M, Wisniewski S, Lopez OL, et al. Plasma and cerebrospinal fluid alpha1-antichymotrypsin levels in Alzheimer’s disease: correlation with cognitive impairment. Ann Neurol. 2003;53(1):81–90. doi:10.1002/ana.10414.PubMed

167.

Manral P, Sharma P, Hariprasad G, Chandralekha, Tripathi M, Srinivasan A. Can apolipoproteins and complement factors be biomarkers of Alzheimer’s disease? Curr Alzheimer Res. 2012;9(8):935–43.PubMed

168.

Lo CY, Wang PN, Chou KH, Wang J, He Y, Lin CP. Diffusion tensor tractography reveals abnormal topological organization in structural cortical networks in Alzheimer’s disease. J Neurosci. 2010;30(50):16876–85. doi:10.1523/JNEUROSCI.4136-10.2010.PubMed

169.

Chien DT, Szardenings AK, Bahri S, Walsh JC, Mu F, Xia C, et al. Early clinical PET imaging results with the novel PHF-tau radioligand [F18]-T808. J Alzheimers Dis. 2013. doi:10.3233/JAD-130098.PubMed

170.

Grimmer T, Alexopoulos P, Tsolakidou A, Guo LH, Henriksen G, Yousefi BH, et al. Cerebrospinal fluid BACE1 activity and brain amyloid load in Alzheimer’s disease. ScientificWorldJournal. 2012;2012:712048. doi:10.1100/2012/712048.PubMedCentralPubMed

171.

Lewczuk P, Kornhuber J, Vanderstichele H, Vanmechelen E, Esselmann H, Bibl M, et al. Multiplexed quantification of dementia biomarkers in the CSF of patients with early dementias and MCI: a multicenter study. Neurobiol Aging. 2008;29(6):812–8. doi:10.1016/j.neurobiolaging.2006.12.010.PubMed

172.

Finehout EJ, Franck Z, Lee KH. Complement protein isoforms in CSF as possible biomarkers for neurodegenerative disease. Dis Mark. 2005;21(2):93–101.

Titel: Biomarker Modelling of Early Molecular Changes in Alzheimer’s Disease
verfasst von: Ross W. Paterson
Jamie Toombs
Catherine F. Slattery
Jonathan M. Schott
Henrik Zetterberg
Publikationsdatum: 01.04.2014
Verlag: Springer International Publishing
Erschienen in: Molecular Diagnosis & Therapy / Ausgabe 2/2014
Print ISSN: 1177-1062
Elektronische ISSN: 1179-2000
DOI: https://doi.org/10.1007/s40291-013-0069-9

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2014

Utilizing Pharmacogenetics in Psychiatry: the Time Has Come

Circulating Melanoma Cells in the Diagnosis and Monitoring of Melanoma: An Appraisal of Clinical Potential

Sensitive Solid-Phase Detection of Donor-Specific Antibodies as an Aid Highly Relevant to Improving Allograft Outcomes

Circulating MicroRNAs in Drug Safety Assessment for Hepatic and Cardiovascular Toxicity: The Latest Biomarker Frontier?

The Effect of Genetic Polymorphisms of Cytochrome P450 CYP2C9, CYP2C19, and CYP2D6 on Drug-Resistant Epilepsy in Turkish Children