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01.12.2015 | Original Communication

Dissecting IWG-2 typical and atypical Alzheimer’s disease: insights from cerebrospinal fluid analysis

verfasst von: Ross W. Paterson, Jamie Toombs, Catherine F. Slattery, Jennifer M. Nicholas, Ulf Andreasson, Nadia K. Magdalinou, Kaj Blennow, Jason D. Warren, Cath J. Mummery, Martin N. Rossor, Michael P. Lunn, Sebastian J. Crutch, Nick C. Fox, Henrik Zetterberg, Jonathan M. Schott

Erschienen in: Journal of Neurology | Ausgabe 12/2015

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Abstract

Pathobiological factors underlying phenotypic diversity in Alzheimer’s disease (AD) are incompletely understood. We used an extended cerebrospinal fluid (CSF) panel to explore differences between “typical” with “atypical” AD and between amnestic, posterior cortical atrophy, logopenic aphasia and frontal variants. We included 97 subjects fulfilling International Working Group-2 research criteria for AD of whom 61 had “typical” AD and 36 “atypical” syndromes, and 30 controls. CSF biomarkers included total tau (T-tau), phosphorylated tau (P-tau), amyloid β1-42, amyloid βX-38/40/42, YKL-40, neurofilament light (NFL), and amyloid precursor proteins α and β. The typical and atypical groups were matched for age, sex, severity and rate of cognitive decline and had similar biomarker profiles, with the exception of NFL which was higher in the atypical group (p = 0.03). Sub-classifying the atypical group into its constituent clinical syndromes, posterior cortical atrophy was associated with the lowest T-tau [604.4 (436.8–675.8) pg/mL], P-tau (79.8 ± 21.8 pg/L), T-tau/Aβ1-42 ratio [2.3 (1.4–2.6)], AβX-40/X-42 ratio (22.1 ± 5.8) and rate of cognitive decline [1.9 (0.75–4.25) MMSE points/year]. Conversely, the frontal variant group had the highest levels of T-tau [1185.4 (591.7–1329.3) pg/mL], P-tau (116.4 ± 45.4 pg/L), T-tau/Aβ1-42 ratio [5.2 (3.3–6.9)] and AβX-40/X-42 ratio (27.9 ± 7.5), and rate of cognitive decline. Whilst on a group level IWG-2 “typical” and “atypical” AD share similar CSF profiles, which are very different from controls, atypical AD is a heterogeneous entity with evidence for subtle differences in amyloid processing and neurodegeneration between different clinical syndromes. These findings also have practical implications for the interpretation of clinical CSF biomarker results.

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Blennow K, Wallin A, Gottfries CG (1991) Presence of parietotemporal symptomatology distinguishes early and late onset Alzheimers-disease. Int J Geriatr Psychiatry 6(3):147–154. doi:10.1002/gps.930060306 CrossRef

Koedam EL, Lauffer V, van der Vlies AE, van der Flier WM, Scheltens P, Pijnenburg YA (2010) Early-versus late-onset Alzheimer’s disease: more than age alone. J Alzheimer’s Dis 19(4):1401–1408. doi:10.3233/JAD-2010-1337

Benson DF, Davis RJ, Snyder BD (1988) Posterior cortical atrophy. Arch Neurol 45(7):789–793CrossRefPubMed

Mendez MF, Ghajarania M, Perryman KM (2002) Posterior cortical atrophy: clinical characteristics and differences compared to Alzheimer’s disease. Dement Geriatr Cogn Disord 14(1):33–40. doi:10.1159/000058331 CrossRefPubMed

Crutch SJ, Lehmann M, Schott JM, Rabinovici GD, Rossor MN, Fox NC (2012) Posterior cortical atrophy. Lancet Neurol 11(2):170–178. doi:10.1016/S1474-4422(11)70289-7 PubMedCentralCrossRefPubMed

Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF, Manes F, Dronkers NF, Vandenberghe R, Rascovsky K, Patterson K, Miller BL, Knopman DS, Hodges JR, Mesulam MM, Grossman M (2011) Classification of primary progressive aphasia and its variants. Neurology 76(11):1006–1014. doi:10.1212/WNL.0b013e31821103e6 PubMedCentralCrossRefPubMed

Dubois B, Feldman HH, Jacova C, Hampel H, Molinuevo JL, Blennow K, DeKosky ST, Gauthier S, Selkoe D, Bateman R, Cappa S, Crutch S, Engelborghs S, Frisoni GB, Fox NC, Galasko D, Habert MO, Jicha GA, Nordberg A, Pasquier F, Rabinovici G, Robert P, Rowe C, Salloway S, Sarazin M, Epelbaum S, de Souza LC, Vellas B, Visser PJ, Schneider L, Stern Y, Scheltens P, Cummings JL (2014) Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 13(6):614–629. doi:10.1016/S1474-4422(14)70090-0 CrossRefPubMed

Ossenkoppele R, Schonhaut DR, Baker SL, O’Neil JP, Janabi M, Ghosh PM, Santos M, Miller ZA, Bettcher BM, Gorno-Tempini ML, Miller BL, Jagust WJ, Rabinovici GD (2015) Tau, amyloid, and hypometabolism in a patient with posterior cortical atrophy. Ann Neurol 77(2):338–342. doi:10.1002/ana.24321 PubMedCentralCrossRefPubMed

Lehmann M, Crutch SJ, Ridgway GR, Ridha BH, Barnes J, Warrington EK, Rossor MN, Fox NC (2011) Cortical thickness and voxel-based morphometry in posterior cortical atrophy and typical Alzheimer’s disease. Neurobiol Aging 32(8):1466–1476. doi:10.1016/j.neurobiolaging.2009.08.017 CrossRefPubMed

10.

Madhavan A, Whitwell JL, Weigand SD, Duffy JR, Strand EA, Machulda MM, Tosakulwong N, Senjem ML, Gunter JL, Lowe VJ, Petersen RC, Jack CR Jr, Josephs KA (2013) FDG PET and MRI in logopenic primary progressive aphasia versus dementia of the Alzheimer’s type. PLoS One 8(4):e62471. doi:10.1371/journal.pone.0062471 PubMedCentralCrossRefPubMed

11.

Lehmann M, Ghosh PM, Madison C, Laforce R Jr, Corbetta-Rastelli C, Weiner MW, Greicius MD, Seeley WW, Gorno-Tempini ML, Rosen HJ, Miller BL, Jagust WJ, Rabinovici GD (2013) Diverging patterns of amyloid deposition and hypometabolism in clinical variants of probable Alzheimer’s disease. Brain 136(Pt 3):844–858. doi:10.1093/brain/aws327 PubMedCentralCrossRefPubMed

12.

Schott JM, Ridha BH, Crutch SJ, Healy DG, Uphill JB, Warrington EK, Rossor MN, Fox NC (2006) Apolipoprotein e genotype modifies the phenotype of Alzheimer disease. Arch Neurol 63(1):155–156. doi:10.1001/archneur.63.1.155 CrossRefPubMed

13.

Carrasquillo MM, Khan Q, Murray ME, Krishnan S, Aakre J, Pankratz VS, Nguyen T, Ma L, Bisceglio G, Petersen RC, Younkin SG, Dickson DW, Boeve BF, Graff-Radford NR, Ertekin-Taner N (2014) Late-onset Alzheimer disease genetic variants in posterior cortical atrophy and posterior AD. Neurology 82(16):1455–1462. doi:10.1212/WNL.0000000000000335 PubMedCentralCrossRefPubMed

14.

van der Flier WM, Schoonenboom SN, Pijnenburg YA, Fox NC, Scheltens P (2006) The effect of APOE genotype on clinical phenotype in Alzheimer disease. Neurology 67(3):526–527. doi:10.1212/01.wnl.0000228222.17111.2a CrossRefPubMed

15.

Strozyk D, Blennow K, White LR, Launer LJ (2003) CSF Abeta 42 levels correlate with amyloid-neuropathology in a population-based autopsy study. Neurology 60(4):652–656CrossRefPubMed

16.

Palmqvist S, Zetterberg H, Blennow K, Vestberg S, Andreasson U, Brooks DJ, Owenius R, Hagerstrom D, Wollmer P, Minthon L, Hansson O (2014) Accuracy of brain amyloid detection in clinical practice using cerebrospinal fluid beta-amyloid 42: a cross-validation study against amyloid positron emission tomography. JAMA Neurol 71(10):1282–1289. doi:10.1001/jamaneurol.2014.1358 CrossRefPubMed

17.

Blennow K, Hampel H, Weiner M, Zetterberg H (2010) Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 6(3):131–144. doi:10.1038/nrneurol.2010.4 CrossRefPubMed

18.

Hampel H, Burger K, Pruessner JC, Zinkowski R, DeBernardis J, Kerkman D, Leinsinger G, Evans AC, Davies P, Moller HJ, Teipel SJ (2005) Correlation of cerebrospinal fluid levels of tau protein phosphorylated at threonine 231 with rates of hippocampal atrophy in Alzheimer disease. Arch Neurol 62(5):770–773. doi:10.1001/archneur.62.5.770 CrossRefPubMed

19.

Buerger K, Ewers M, Pirttila T, Zinkowski R, Alafuzoff I, Teipel SJ, DeBernardis J, Kerkman D, McCulloch C, Soininen H, Hampel H (2006) CSF phosphorylated tau protein correlates with neocortical neurofibrillary pathology in Alzheimer’s disease. Brain 129(Pt 11):3035–3041. doi:10.1093/brain/awl269 CrossRefPubMed

20.

Craig-Schapiro R, Perrin RJ, Roe CM, Xiong C, Carter D, Cairns NJ, Mintun MA, Peskind ER, Li G, Galasko DR, Clark CM, Quinn JF, D’Angelo G, Malone JP, Townsend RR, Morris JC, Fagan AM, Holtzman DM (2010) YKL-40: a novel prognostic fluid biomarker for preclinical Alzheimer’s disease. Biol Psychiatry 68(10):903–912. doi:10.1016/j.biopsych.2010.08.025 PubMedCentralCrossRefPubMed

21.

Sjogren M, Rosengren L, Minthon L, Davidsson P, Blennow K, Wallin A (2000) Cytoskeleton proteins in CSF distinguish frontotemporal dementia from AD. Neurology 54(10):1960–1964CrossRefPubMed

22.

Lewczuk P, Kornhuber J, Vanmechelen E, Peters O, Heuser I, Maier W, Jessen F, Burger K, Hampel H, Frolich L, Henn F, Falkai P, Ruther E, Jahn H, Luckhaus C, Perneczky R, Schmidtke K, Schroder J, Kessler H, Pantel J, Gertz HJ, Vanderstichele H, de Meyer G, Shapiro F, Wolf S, Bibl M, Wiltfang J (2010) Amyloid beta peptides in plasma in early diagnosis of Alzheimer’s disease: a multicenter study with multiplexing. Exp Neurol 223(2):366–370. doi:10.1016/j.expneurol.2009.07.024 CrossRefPubMed

23.

Brinkmalm G, Brinkmalm A, Bourgeois P, Persson R, Hansson O, Portelius E, Mercken M, Andreasson U, Parent S, Lipari F, Ohrfelt A, Bjerke M, Minthon L, Zetterberg H, Blennow K, Nutu M (2013) Soluble amyloid precursor protein alpha and beta in CSF in Alzheimer’s disease. Brain Res 1513:117–126. doi:10.1016/j.brainres.2013.03.019 CrossRefPubMed

24.

Bibl M, Gallus M, Welge V, Esselmann H, Wiltfang J (2012) Aminoterminally truncated and oxidized amyloid-beta peptides in the cerebrospinal fluid of Alzheimer’s disease patients. J Alzheimer’s Dis 29(4):809–816. doi:10.3233/JAD-2012-111796

25.

Duits FH, Teunissen CE, Bouwman FH, Visser PJ, Mattsson N, Zetterberg H, Blennow K, Hansson O, Minthon L, Andreasen N, Marcusson J, Wallin A, Rikkert MO, Tsolaki M, Parnetti L, Herukka SK, Hampel H, De Leon MJ, Schroder J, Aarsland D, Blankenstein MA, Scheltens P, van der Flier WM (2014) The cerebrospinal fluid “Alzheimer profile”: easily said, but what does it mean? Alzheimer’s Dement 10(6):713–723. doi:10.1016/j.jalz.2013.12.023 CrossRef

26.

Tang-Wai DF, Graff-Radford NR, Boeve BF, Dickson DW, Parisi JE, Crook R, Caselli RJ, Knopman DS, Petersen RC (2004) Clinical, genetic, and neuropathologic characteristics of posterior cortical atrophy. Neurology 63(7):1168–1174CrossRefPubMed

27.

Waldemar G, Dubois B, Emre M, Scheltens P, Tariska P, Rossor M (2000) Diagnosis and management of Alzheimer’s disease and other disorders associated with dementia. The role of neurologists in Europe. European Federation of Neurological Societies. Eur J Neurol 7(2):133–144CrossRefPubMed

28.

Knopman DS, DeKosky ST, Cummings JL, Chui H, Corey-Bloom J, Relkin N, Small GW, Miller B, Stevens JC (2001) Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 56(9):1143–1153CrossRefPubMed

29.

Rossor MN, Fox NC, Mummery CJ, Schott JM, Warren JD (2010) The diagnosis of young-onset dementia. Lancet Neurol 9(8):793–806. doi:10.1016/s1474-4422(10)70159-9 PubMedCentralCrossRefPubMed

30.

Paterson RW, Toombs J, Slattery CF, Schott JM, Zetterberg H (2014) Biomarker modelling of early molecular changes in Alzheimer’s disease. Mol Diagn Ther 18(2):213–227. doi:10.1007/s40291-013-0069-9 CrossRefPubMed

31.

Birks J (2006) Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. doi:10.1002/14651858.CD005593

32.

Skillback T, Farahmand B, Bartlett JW, Rosen C, Mattsson N, Nagga K, Kilander L, Religa D, Wimo A, Winblad B, Rosengren L, Schott JM, Blennow K, Eriksdotter M, Zetterberg H (2014) CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival. Neurology 83(21):1945–1953. doi:10.1212/WNL.0000000000001015 CrossRefPubMed

33.

Scherling CS, Hall T, Berisha F, Klepac K, Karydas A, Coppola G, Kramer JH, Rabinovici G, Ahlijanian M, Miller BL, Seeley W, Grinberg LT, Rosen H, Meredith J Jr, Boxer AL (2014) Cerebrospinal fluid neurofilament concentration reflects disease severity in frontotemporal degeneration. Ann Neurol 75(1):116–126. doi:10.1002/ana.24052 PubMedCentralCrossRefPubMed

34.

Ossenkoppele R, Mattsson N, Teunissen CE, Barkhof F, Pijnenburg Y, Scheltens P, van der Flier WM, Rabinovici GD (2015) Cerebrospinal fluid biomarkers and cerebral atrophy in distinct clinical variants of probable Alzheimer’s disease. Neurobiol Aging. doi:10.1016/j.neurobiolaging.2015.04.011 PubMedCentralPubMed

35.

Seguin J, Formaglio M, Perret-Liaudet A, Quadrio I, Tholance Y, Rouaud O, Thomas-Anterion C, Croisile B, Mollion H, Moreaud O, Salzmann M, Dorey A, Bataillard M, Coste MH, Vighetto A, Krolak-Salmon P (2011) CSF biomarkers in posterior cortical atrophy. Neurology 76(21):1782–1788. doi:10.1212/WNL.0b013e31821ccc98 CrossRefPubMed

36.

de Souza LC, Corlier F, Habert MO, Uspenskaya O, Maroy R, Lamari F, Chupin M, Lehericy S, Colliot O, Hahn-Barma V, Samri D, Dubois B, Bottlaender M, Sarazin M (2011) Similar amyloid-beta burden in posterior cortical atrophy and Alzheimer’s disease. Brain 134(Pt 7):2036–2043. doi:10.1093/brain/awr130 CrossRefPubMed

37.

Coppi E, Ferrari L, Santangelo R, Caso F, Pinto P, Passerini G, Comi G, Magnani G (2014) Further evidence about the crucial role of CSF biomarkers in diagnosis of posterior cortical atrophy. Neurological Sci 35(5):785–787. doi:10.1007/s10072-014-1644-5 CrossRef

38.

Baumann TP, Duyar H, Sollberger M, Kuhle J, Regeniter A, Gomez-Mancilla B, Schmidtke K, Monsch AU (2010) CSF-tau and CSF-Abeta(1-42) in posterior cortical atrophy. Dement Geriatr Cogn Disord 29(6):530–533. doi:10.1159/000314679 CrossRefPubMed

39.

Formaglio M, Costes N, Seguin J, Tholance Y, Le Bars D, Roullet-Solignac I, Mercier B, Krolak-Salmon P, Vighetto A (2011) In vivo demonstration of amyloid burden in posterior cortical atrophy: a case series with PET and CSF findings. J Neurol 258(10):1841–1851. doi:10.1007/s00415-011-6030-0 CrossRefPubMed

40.

Beaufils E, Dufour-Rainfray D, Hommet C, Brault F, Cottier JP, Ribeiro MJ, Mondon K, Guilloteau D (2013) Confirmation of the amyloidogenic process in posterior cortical atrophy: value of the Abeta42/Abeta40 ratio. J Alzheimer’s Dis 33(3):775–780. doi:10.3233/JAD-2012-121267

41.

Teng E, Yamasaki TR, Tran M, Hsiao JJ, Sultzer DL, Mendez MF (2014) Cerebrospinal fluid biomarkers in clinical subtypes of early-onset Alzheimer’s disease. Dement Geriatr Cogn Disord 37(5–6):307–314. doi:10.1159/000355555 PubMedCentralCrossRefPubMed

42.

Hampel H, Blennow K, Shaw LM, Hoessler YC, Zetterberg H, Trojanowski JQ (2010) Total and phosphorylated tau protein as biological markers of Alzheimer’s disease. Exp Gerontol 45(1):30–40. doi:10.1016/j.exger.2009.10.010 PubMedCentralCrossRefPubMed

43.

Riemenschneider M, Wagenpfeil S, Vanderstichele H, Otto M, Wiltfang J, Kretzschmar H, Vanmechelen E, Forstl H, Kurz A (2003) Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt-Jakob disease from other dementias. Mol Psychiatry 8(3):343–347. doi:10.1038/sj.mp.4001220 CrossRefPubMed

44.

Tapiola T, Overmyer M, Lehtovirta M, Helisalmi S, Ramberg J, Alafuzoff I, Riekkinen P Sr, Soininen H (1997) The level of cerebrospinal fluid tau correlates with neurofibrillary tangles in Alzheimer’s disease. NeuroReport 8(18):3961–3963CrossRefPubMed

45.

Rosenbloom MH, Alkalay A, Agarwal N, Baker SL, O’Neil JP, Janabi M, Yen IV, Growdon M, Jang J, Madison C, Mormino EC, Rosen HJ, Gorno-Tempini ML, Weiner MW, Miller BL, Jagust WJ, Rabinovici GD (2011) Distinct clinical and metabolic deficits in PCA and AD are not related to amyloid distribution. Neurology 76(21):1789–1796. doi:10.1212/WNL.0b013e31821cccad PubMedCentralCrossRefPubMed

46.

Leyton CE, Villemagne VL, Savage S, Pike KE, Ballard KJ, Piguet O, Burrell JR, Rowe CC, Hodges JR (2011) Subtypes of progressive aphasia: application of the International Consensus Criteria and validation using beta-amyloid imaging. Brain 134(Pt 10):3030–3043. doi:10.1093/brain/awr216 CrossRefPubMed

47.

Levine DN, Lee JM, Fisher CM (1993) The visual variant of Alzheimer’s disease: a clinicopathologic case study. Neurology 43(2):305–313CrossRefPubMed

48.

Galton CJ, Patterson K, Xuereb JH, Hodges JR (2000) Atypical and typical presentations of Alzheimer’s disease: a clinical, neuropsychological, neuroimaging and pathological study of 13 cases. Brain 123(Pt 3):484–498CrossRefPubMed

49.

Kanne SM, Balota DA, Storandt M, McKeel DW Jr, Morris JC (1998) Relating anatomy to function in Alzheimer’s disease: neuropsychological profiles predict regional neuropathology 5 years later. Neurology 50(4):979–985CrossRefPubMed

50.

Whitwell JL, Petersen RC, Negash S, Weigand SD, Kantarci K, Ivnik RJ, Knopman DS, Boeve BF, Smith GE, Jack CR Jr (2007) Patterns of atrophy differ among specific subtypes of mild cognitive impairment. Arch Neurol 64(8):1130–1138. doi:10.1001/archneur.64.8.1130 PubMedCentralCrossRefPubMed

51.

Verbeek MM, Kremer BP, Rikkert MO, Van Domburg PH, Skehan ME, Greenberg SM (2009) Cerebrospinal fluid amyloid beta(40) is decreased in cerebral amyloid angiopathy. Ann Neurol 66(2):245–249. doi:10.1002/ana.21694 PubMedCentralCrossRefPubMed

52.

Wiltfang J, Esselmann H, Bibl M, Smirnov A, Otto M, Paul S, Schmidt B, Klafki HW, Maler M, Dyrks T, Bienert M, Beyermann M, Ruther E, Kornhuber J (2002) Highly conserved and disease-specific patterns of carboxyterminally truncated Abeta peptides 1-37/38/39 in addition to 1-40/42 in Alzheimer’s disease and in patients with chronic neuroinflammation. J Neurochem 81(3):481–496CrossRefPubMed

53.

Welge V, Fiege O, Lewczuk P, Mollenhauer B, Esselmann H, Klafki HW, Wolf S, Trenkwalder C, Otto M, Kornhuber J, Wiltfang J, Bibl M (2009) Combined CSF tau, p-tau181 and amyloid-beta 38/40/42 for diagnosing Alzheimer’s disease. J Neural Transm 116(2):203–212. doi:10.1007/s00702-008-0177-6 CrossRefPubMed

54.

Hansson O, Buchhave P, Zetterberg H, Blennow K, Minthon L, Warkentin S (2009) Combined rCBF and CSF biomarkers predict progression from mild cognitive impairment to Alzheimer’s disease. Neurobiol Aging 30(2):165–173. doi:10.1016/j.neurobiolaging.2007.06.009 CrossRefPubMed

55.

Struyfs H, Molinuevo JL, Martin JJ, De Deyn PP, Engelborghs S (2014) Validation of the AD-CSF-index in autopsy-confirmed Alzheimer’s disease patients and healthy controls. J Alzheimer’s Dis 41(3):903–909. doi:10.3233/JAD-131085

56.

Fukuyama R, Mizuno T, Mori S, Nakajima K, Fushiki S, Yanagisawa K (2000) Age-dependent change in the levels of Abeta40 and Abeta42 in cerebrospinal fluid from control subjects, and a decrease in the ratio of Abeta42 to Abeta40 level in cerebrospinal fluid from Alzheimer’s disease patients. Eur Neurol 43(3):155–160. doi:10.1159/000008156 CrossRefPubMed

57.

Wiltfang J, Esselmann H, Bibl M, Hull M, Hampel H, Kessler H, Frolich L, Schroder J, Peters O, Jessen F, Luckhaus C, Perneczky R, Jahn H, Fiszer M, Maler JM, Zimmermann R, Bruckmoser R, Kornhuber J, Lewczuk P (2007) Amyloid beta peptide ratio 42/40 but not A beta 42 correlates with phospho-Tau in patients with low- and high-CSF A beta 40 load. J Neurochem 101(4):1053–1059. doi:10.1111/j.1471-4159.2006.04404.x CrossRefPubMed

58.

Storey E, Slavin MJ, Kinsella GJ (2002) Patterns of cognitive impairment in Alzheimer’s disease: assessment and differential diagnosis. Front Biosci 7:e155–184CrossRefPubMed

59.

Aries MJ, Le Bastard N, Debruyne H, Van Buggenhout M, Nagels G, De Deyn PP, Engelborghs S (2010) Relation between frontal lobe symptoms and dementia severity within and across diagnostic dementia categories. Int J Geriatr Psychiatry 25(11):1186–1195. doi:10.1002/gps.2481 CrossRefPubMed

60.

Taylor KI, Probst A, Miserez AR, Monsch AU, Tolnay M (2008) Clinical course of neuropathologically confirmed frontal-variant Alzheimer’s disease. Nat Clin Pract Neurol 4(4):226–232. doi:10.1038/ncpneuro0746 PubMed

61.

Woodward M, Jacova C, Black SE, Kertesz A, Mackenzie IR, Feldman H, group Ai (2010) Differentiating the frontal variant of Alzheimer’s disease. Int J Geriatr Psychiatry 25(7):732–738. doi:10.1002/gps.2415 CrossRefPubMed

62.

Johnson JK, Head E, Kim R, Starr A, Cotman CW (1999) Clinical and pathological evidence for a frontal variant of Alzheimer disease. Arch Neurol 56(10):1233–1239CrossRefPubMed

63.

Schott JM, Revesz T (2013) Inflammation in Alzheimer’s disease: insights from immunotherapy. Brain 136(Pt 9):2654–2656. doi:10.1093/brain/awt231 CrossRefPubMed

64.

Rosen C, Hansson O, Blennow K, Zetterberg H (2013) Fluid biomarkers in Alzheimer’s disease—current concepts. Mol Neurodegener 8:20. doi:10.1186/1750-1326-8-20 PubMedCentralCrossRefPubMed

Titel: Dissecting IWG-2 typical and atypical Alzheimer’s disease: insights from cerebrospinal fluid analysis
verfasst von: Ross W. Paterson
Jamie Toombs
Catherine F. Slattery
Jennifer M. Nicholas
Ulf Andreasson
Nadia K. Magdalinou
Kaj Blennow
Jason D. Warren
Cath J. Mummery
Martin N. Rossor
Michael P. Lunn
Sebastian J. Crutch
Nick C. Fox
Henrik Zetterberg
Jonathan M. Schott
Publikationsdatum: 01.12.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Neurology / Ausgabe 12/2015
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-015-7904-3

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Dissecting IWG-2 typical and atypical Alzheimer’s disease: insights from cerebrospinal fluid analysis

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