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Acta Neuropathologica

Erschienen in:

01.08.2013 | Correspondence

Amyloid-β may be released from non-junctional varicosities of axons generated from abnormal tau-containing brainstem nuclei in sporadic Alzheimer’s disease: a hypothesis

verfasst von: Heiko Braak, Kelly Del Tredici

Erschienen in: Acta Neuropathologica | Ausgabe 2/2013

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Excerpt

All cases of sporadic Alzheimer’s disease (AD) are neuropathologically characterized by disease-related lesions that develop at specific sites in the human brain and gradually disperse from there into hitherto uninvolved regions [5, 14, 24, 35‐37, 44]. Central to this pathological process are abnormal alterations of the neuronal cytoskeleton that consist mainly of hyperphosphorylated and aggregated tau protein [17, 21, 25‐27, 30, 31]. Involved nerve cells first can be seen in brainstem nuclei that diffusely project to the cerebral cortex. Among others, these include the noradrenergic locus coeruleus, the serotonergic upper raphe nuclei, and the cholinergic magnocellular nuclei of the basal forebrain [8]. Later on, in the pathological process, the intraneuronal inclusions are accompanied by extracellular plaque-like deposits of a second abnormal protein, amyloid β (Aβ) [10, 11, 42]. …

Agnati LF, Bjelke B, Fuxe K (1995) Volume versus wiring transmission in the brain: a new theoretical frame of neuropsychopharmacology. Med Res Rev 15:33–45PubMedCrossRef

Beach TG, Sue LI, Walker DG et al (2012) Striatal amyloid plaque density predicts Braak neurofibrillary stage and clinicopathological Alzheimer’s disease: implications for amyloid imaging. J Alzheimers Dis 28:869–876PubMed

Blennow K, Zetterberg H, Fagan AM (2012) Fluid biomarkers in Alzheimer disease. Cold Spring Harb Perspect Med 2:a006221PubMedCrossRef

Braak H, Braak E (1990) Alzheimer’s disease: amyloid deposits and neurofibrillary changes in the striatum. J Neuropathol Exp Neurol 49:215–224PubMedCrossRef

Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259PubMedCrossRef

Braak H, Del Tredici K (2004) Alzheimer’s disease: intraneuronal alterations precede insoluble amyloid-β formation. Neurobiol Aging 25:713–718PubMedCrossRef

Braak H, Del Tredici K (2011) The pathological process underlying Alzheimer’s disease in individuals under thirty. Acta Neuropathol 121:171–181PubMedCrossRef

Braak H, Del Tredici K (2012) Where, when, and in what form does sporadic Alzheimer’s disease begin? Curr Opin Neurol 25:708–714PubMedCrossRef

Braak H, Braak E, Bohl J et al (1989) Alzheimer’s disease: amyloid plaques in the cerebellum. J Neurol Sci 93:277–287PubMedCrossRef

10.

Braak H, Thal DR, Ghebremedhin E et al (2011) Stages of the pathological process in Alzheimer’ disease. J Neuropathol Exp Neurol 70:960–969PubMedCrossRef

11.

Braak H, Zetterberg H, Del Tredici K, Blennow K (2013) Intraneuronal tau aggregation precedes diffuse plaque deposition, but amyloid-β changes occur before increases of tau in cerebrospinal fluid. Acta Neuropathol. doi:10.1007/s00401-013-1139-0

12.

Busch C, Bohl J, Ohm TG (1997) Spatial, temporal and numeric analysis of Alzheimer changes in the nucleus coeruleus. Neurobiol Aging 18:401–406PubMedCrossRef

13.

Cohen Z, Molinatti G, Hamel E (1997) Astroglial and vascular interactions of noradrenaline terminals in the rat cerebral cortex. J Cereb Blood Flow Metab 17:894–904PubMedCrossRef

14.

Duyckaerts C, Delatour B, Potier MC (2009) Classification and basic pathology of Alzheimer’s disease. Acta Neuropathol 118:5–36PubMedCrossRef

15.

Elobeid A, Soininen H, Alafuzoff I (2012) Hyperphosphorylated tau in young and middle-aged subjects. Acta Neuropathol 123:97–104PubMedCrossRef

16.

German DC, White CL, Sparkman DR (1987) Alzheimer’s disease: neurofibrillary tangles in nuclei that project to the cerebral cortex. Neurosci 21:305–312CrossRef

17.

Goedert M, Klug A, Crowther RA (2006) Tau protein, the paired helical filament and Alzheimer’s disease. J Alzheimers Dis 9(Suppl):195–207PubMed

18.

Grinberg LT, Rüb U, Ferretti REL et al (2009) The dorsal raphe nucleus shows phospho-tau neurofibrillary changes before the transentorhinal region in Alzheimer’s disease. A precocious onset? Neuropathol Appl Neurobiol 35:406–416PubMedCrossRef

19.

Grinberg LT, Korczyn AD, Heinsen H (2012) Cerebral amyloid angiopathy impact on endothelium. Exp Gerontol 47:838–842PubMedCrossRef

20.

Grudzien A, Shaw P, Weintraub S et al (2007) Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer’s disease. Neurobiol Aging 28:327–335PubMedCrossRef

21.

Grundke-Iqbal I, Iqbal K, Tung Y et al (1986) Abnormal phosphorylation of the microtubule-associated proteinτ (tau) in Alzheimer cytoskeletal pathology. Proc Nat Acad Sci USA 83:4913–4917PubMedCrossRef

22.

Haass C, Kaether C, Thinakaran G et al (2012) Trafficking and proteolytic processing of APP. Cold Spring Harb Perspect Med 2:a006270PubMedCrossRef

23.

Haglund M, Sjöbeck M, Englund E (2006) Locus ceruleus degeneration is ubiquitous in Alzheimer’s disease: possible implications for diagnosis and treatment. Neuropathology 26:528–532PubMedCrossRef

24.

Hyman BT, Phelps CH, Beach TG et al (2012) National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement 8:1–13PubMedCrossRef

25.

Iqbal K, Grundke-Iqbal I (2008) Alzheimer neurofibrillary degeneration: significance, etiopathogenesis, therapeutics and prevention. J Cell Mol Med 12:38–55PubMedCrossRef

26.

Iqbal K, Alonso AC, Gong CX et al (1994) Mechanism of neurofibrillary degeneration in Alzheimer’s disease. Mol Neurobiol 9:119–123PubMedCrossRef

27.

Iqbal K, Liu F, Gong CX et al (2009) Mechanisms of tau-induced neurodegeneration. Acta Neuropathol 118:53–69PubMedCrossRef

28.

Iseki E, Matsushita M, Kosaka K et al (1989) Distribution and morphology of brain stem plaques in Alzheimer’s disease. Acta Neuropathol 78:131–136PubMedCrossRef

29.

Kovács T, Cairns NJ, Lantos PL (1999) β-amyloid deposition and neurofibrillary tangle formation in the olfactory bulb in ageing and Alzheimer’s disease. Neuropathol Appl Neurobiol 25:481–491PubMedCrossRef

30.

Mandelkow EM, Mandelkow E (2012) Biochemistry and cell biology of tau protein in neurofibrillary degeneration. Cold Spring Harb Perspect Med 2:a006247PubMedCrossRef

31.

Mandelkow E, von Bergen M, Biernat J et al (2007) Structural principles of tau and the paired helical filaments of Alzheimer’s disease. Brain Pathol 17:83–90PubMedCrossRef

32.

Masters CL, Beyreuther K (2006) Pathways to the discovery of the neuronal origin and proteolytic biogenesis of Aβ amyloid of Alzheimer’s disease. In: Alzheimer: 100 years and beyond. Springer, Berlin, pp 143–149

33.

Masters CL, Selkow DJ (2012) Biochemistry of amyloid β-protein and amyloid deposits in Alzheimer’s disease. Cold Spring Harb Perspect Med 2:a006262PubMedCrossRef

34.

Mesulam MM, Shaw P, Mash D et al (2004) Cholinergic nucleus basalis tauopathy emerges early in the aging-MCI-AD continuum. Ann Neurol 55:815–828PubMedCrossRef

35.

Montine TJ, Phelps CH, Beach TG et al (2012) National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach. Acta Neuropathol 123:1–11PubMedCrossRef

36.

Nelson PT, Jicha GA, Schmitt FA et al (2007) Clinicopathologic correlations in a large Alzheimer disease center autopsy cohort: neuritic plaques and neurofibrillary tangles “do count” when staging disease severity. J Neuropathol Exp Neurol 66:1136–1146PubMedCrossRef

37.

Nelson PT, Head E, Schmitt FA et al (2011) Alzheimer’s disease is not “brain aging”: neuropathological, genetic, and epidemiological human studies. Acta Neuropathol 121:571–587PubMedCrossRef

38.

O’Donnell J, Zeppenfeld D, McConnell E et al (2012) Norepinephrine: a neuromodulator that boosts the function of multiple cell types to optimize CNS performance. Neurochem Res 37:2496–2512PubMedCrossRef

39.

Parvizi J, Van Hoesen GW, Damasio A (2001) The selective vulnerability of brainstem nuclei to Alzheimer’s disease. Ann Neurol 49:53–66PubMedCrossRef

40.

Rüb U, Del Tredici K, Schultz C et al (2000) The evolution of Alzheimer’s disease-related cytoskeletal pathology in the human raphe nuclei. Neuropathol Appl Neurobiol 26:553–557PubMedCrossRef

41.

Sassin I, Schultz C, Thal DR et al (2000) Evolution of Alzheimer’s disease-related cytoskeletal changes in the basal nucleus of Meynert. Acta Neuropathol 100:259–269PubMedCrossRef

42.

Schönheit B, Zarski R, Ohm TG (2004) Spatial and temporal relationship between plaques and tangles in Alzheimer-pathology. Neurobiol Aging 25:697–711PubMedCrossRef

43.

Selkoe DJ (1994) Alzheimer’s disease: a central role for amyloid. J Neuropathol Exp Neurol 53:438–447PubMedCrossRef

44.

Serrano-Pozo A, Frosch M, Masliah E et al (2011) Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 1:a006189PubMedCrossRef

45.

Simic G, Stanic G, Mladinov M et al (2009) Does Alzheimer’s disease begin in the brainstem? Neuropathol Appl Neurobiol 35:532–554PubMedCrossRef

46.

Thal DR, Rüb U, Schultz C et al (2000) Sequence of Aβ-protein deposition in the human medial temporal lobe. J Neuropathol Exp Neurol 59:733–748PubMed

47.

Thal DR, Rüb U, Orantes M et al (2002) Phases of Aβ-deposition in the human brain and its relevance for the development of AD. Neurology 58:1791–1800PubMedCrossRef

48.

Vana L, Kanaan NM, Ugwu IC et al (2011) Progression of tau pathology in cholinergic basal forebrain neurons in mild cognitive impairment and Alzheimer’s disease. Am J Pathol 179:2533–2550PubMedCrossRef

49.

Weinshenker D (2008) Functional consequences of locus coeruleus degeneration in Alzheimer’s disease. Curr Alzheimer Res 5:342–345PubMedCrossRef

50.

Yamada M, Naiki H (2012) Cerebral amyloid angiopathy. Prog Mol Biol Transl Sci 107:41–78PubMedCrossRef

51.

Yoshiyama Y, Lee VMY, Trojanowski JQ (2013) Therapeutic strategies for tau mediated neurodegeneration. J Neurol Neurosurg Psychiatry 84:784–795PubMedCrossRef

52.

Zweig RM, Ross CA, Hedreen JC et al (1988) The neuropathology of aminergic nuclei in Alzheimer’s disease. Ann Neurol 24:233–242PubMedCrossRef

Titel: Amyloid-β may be released from non-junctional varicosities of axons generated from abnormal tau-containing brainstem nuclei in sporadic Alzheimer’s disease: a hypothesis
verfasst von: Heiko Braak
Kelly Del Tredici
Publikationsdatum: 01.08.2013
Verlag: Springer Berlin Heidelberg
Erschienen in: Acta Neuropathologica / Ausgabe 2/2013
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-013-1153-2

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