Abnormal neurites containing C-terminally truncated α-synuclein are present in Alzheimer's disease without conventional lewy body pathology

American Journal of Pathology

Volumn 177, Issue 6, 2010, Pages 3037-3050

  Lewis, Karen A ^a,b,c   Su, Yang ^a,b   Jou, Olina ^a,b   Ritchie, Caroline ^a,b   Foong, Chan ^a,b   Hynan, Linda S ^a   White III, Charles L ^a,b   Thomas, Philip J ^b   Hatanpaa, Kimmo J ^a,b  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^c UNIVERSITY OF COLORADO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN;

ALZHEIMER DISEASE; AMINO TERMINAL SEQUENCE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CINGULATE GYRUS; DIFFUSE LEWY BODY DISEASE; HUMAN; HUMAN TISSUE; NEURITE; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN DEGRADATION;

EID: 78650221707     PISSN: 00029440     EISSN: 15252191     Source Type: Journal    
DOI: 10.2353/ajpath.2010.100552     Document Type: Article

References (39)

1. Hoyer W, Cherny D, Subramaniam V, Jovin TM: Impact of the acidic C-terminal region comprising amino acids 109-140 on alpha-synuclein aggregation in vitro. Biochemistry 2004, 43:16233-16242
2. Liu CW, Giasson BI, Lewis KA, Lee VM, Demartino GN, Thomas PJ: A precipitating role for truncated alpha-synuclein and the proteasome in alpha-synuclein aggregation: implications for pathogenesis of Parkinson disease. J Biol Chem 2005, 280:22670-22678
3. Li W, West N, Colla E, Pletnikova O, Troncoso JC, Marsh L, Dawson TM, Jakala P, Hartmann T, Price DL, Lee MK: Aggregation promoting C-terminal truncation of alpha-synuclein is a normal cellular process and is enhanced by the familial Parkinson's disease-linked mutations. Proc Natl Acad Sci USA 2005, 102:2162-2167 (Pubitemid 40262029)
4. Anderson JP, Walker DE, Goldstein JM, de Laat R, Banducci K, Caccavello RJ, Barbour R, Huang J, Kling K, Lee M, Diep L, Keim PS, Shen X, Chataway T, Schlossmacher MG, Seubert P, Schenk D, Sinha S, Gai WP, Chilcote TJ: Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J Biol Chem 2006, 281:29739-29752
5. Daher JP, Ying M, Banerjee R, McDonald RS, Hahn MD, Yang L, Flint Beal M, Thomas B, Dawson VL, Dawson TM, Moore DJ: Conditional transgenic mice expressing C-terminally truncated human alpha-synuclein (alphaSyn119) exhibit reduced striatal dopamine without loss of nigrostriatal pathway dopaminergic neurons. Mol Neurodegener 2009, 4:34
6. Wakamatsu M, Ishii A, Iwata S, Sakagami J, Ukai Y, Ono M, Kanbe D, Muramatsu SI, Kobayashi K, Iwatsubo T, Yoshimoto M: Selective loss of nigral dopamine neurons induced by overexpression of truncated human alpha-synuclein in mice. Neurobiol Aging 2008, 29:574-585
7. Tofaris GK, Garcia Reitbock P, Humby T, Lambourne SL, O'Connell M, Ghetti B, Gossage H, Emson PC, Wilkinson LS, Goedert M, Spillantini MG: Pathological changes in dopaminergic nerve cells of the substantia nigra and olfactory bulb in mice transgenic for truncated human alpha-synuclein(1-120): implications for Lewy body disorders. J Neurosci 2006, 26:3942-3950
8. Bennett MC, Bishop JF, Leng Y, Chock PB, Chase TN, Mouradian MM: Degradation of alpha-synuclein by proteasome. J Biol Chem 1999, 274:33855-33858
9. Mishizen-Eberz AJ, Guttmann RP, Giasson BI, Day GA, 3rd, Hodara R, Ischiropoulos H, Lee VM, Trojanowski JQ, Lynch DR: Distinct cleavage patterns of normal and pathologic forms of alpha-synuclein by calpain I in vitro. J Neurochem 2003, 86:836-847
10. Mishizen-Eberz AJ, Norris EH, Giasson BI, Hodara R, Ischiropoulos H, Lee VM, Trojanowski JQ, Lynch DR: Cleavage of alpha-synuclein by calpain: potential role in degradation of fibrillized and nitrated species of alpha-synuclein. Biochemistry 2005, 44:7818-7829 (Pubitemid 40740765)
11. Sevlever D, Jiang P, Yen SH: Cathepsin D is the main lysosomal enzyme involved in the degradation of alpha-synuclein and generation of its carboxy-terminally truncated species. Biochemistry 2008, 47:9678-9687
12. Culvenor JG, McLean CA, Cutt S, Campbell BC, Maher F, Jakala P, Hartmann T, Beyreuther K, Masters CL, Li QX: Non-Abeta component of Alzheimer's disease amyloid (NAC) revisited. NAC and alpha-synuclein are not associated with Abeta amyloid. Am J Pathol 1999, 155:1173-1181
13. Liu CW, Corboy MJ, DeMartino GN, Thomas PJ: Endoproteolytic activity of the proteasome. Science 2003, 299:408-411
14. Lewis KA, Yaeger A, DeMartino GN, Thomas PJ: Accelerated formation of alpha-synuclein oligomers by concerted action of the 20S proteasome and familial Parkinson mutations. J Bioenerg Biomembr 2010, 42:85-95
15. Uchikado H, Lin WL, DeLucia MW, Dickson DW: Alzheimer disease with amygdala Lewy bodies: a distinct form of alpha-synucleinopathy. J Neuropathol Exp Neurol 2006, 65:685-697
16. Pletnikova O, West N, Lee MK, Rudow GL, Skolasky RL, Dawson TM, Marsh L, Troncoso JC: Abeta deposition is associated with enhanced cortical alpha-synuclein lesions in Lewy body diseases. Neurobiol Aging 2005, 26:1183-1192
17. Giasson BI, Forman MS, Higuchi M, Golbe LI, Graves CL, Kotzbauer PT, Trojanowski JQ, Lee VM: Initiation and synergistic fibrillization of tau and alpha-synuclein. Science 2003, 300:636-640 (Pubitemid 36520587)
18. Geddes JW: alpha-Synuclein: a potent inducer of tau pathology. Exp Neurol 2005, 192:244-250
19. Mamah CE, Lesnick TG, Lincoln SJ, Strain KJ, de Andrade M, Bower JH, Ahlskog JE, Rocca WA, Farrer MJ, Maraganore DM: Interaction of alpha-synuclein and tau genotypes in Parkinson's disease. Ann Neurol 2005, 57:439-443
20. McKeith I, Fairbairn A, Perry R, Thompson P, Perry E: Neuroleptic sensitivity in patients with senile dementia of Lewy body type. Bmj 1992, 305:673-678
21. Liang TC, Luo W, Hsieh JT, Lin SH: Antibody binding to a peptide but not the whole protein by recognition of the C-terminal carboxy group. Arch Biochem Biophys 1996, 329:208-214
22. Jakes R, Crowther RA, Lee VM, Trojanowski JQ, Iwatsubo T, Goedert M: Epitope mapping of LB509, a monoclonal antibody directed against human alpha-synuclein. Neurosci Lett 1999, 269:13-16
23. Guntern R, Bouras C, Hof PR, Vallet PG: An improved thioflavine S method for staining neurofibrillary tangles and senile plaques in Alzheimer's disease. Experientia 1992, 48:8-10
24. Mirra SS, Hart MN, Terry RD: Making the diagnosis of Alzheimer's disease. A primer for practicing pathologists Arch Pathol Lab Med 1993, 117:132-144
25. Braak H, Alafuzoff I, Arzberger T, Kretzschmar H, Del Tredici K: Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol 2006, 112:389-404
26. McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova-Ladinska EB, Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M: Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005, 65:1863-1872
27. Weisman D, McKeith I: Dementia with Lewy bodies. Semin Neurol 2007, 27:42-47
28. Beach TG, Adler CH, Lue L, Sue LI, Bachalakuri J, Henry-Watson J, Sasse J, Boyer S, Shirohi S, Brooks R, Eschbacher J, White CL, 3rd, Akiyama H, Caviness J, Shill HA, Connor DJ, Sabbagh MN, Walker DG: Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction. Acta Neuropathol 2009, 117:613-634
29. Luk KC, Song C, O'Brien P, Stieber A, Branch JR, Brunden KR, Trojanowski JQ, Lee VM: Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells. Proc Natl Acad Sci USA 2009, 106:20051-20056
30. Conway KA, Harper JD, Lansbury PT: Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nat Med 1998, 4:1318-1320
31. Beach TG, White CL, Hamilton RL, Duda JE, Iwatsubo T, Dickson DW, Leverenz JB, Roncaroli F, Buttini M, Hladik CL, Sue LI, Noorigian JV, Adler CH: Evaluation of alpha-synuclein immunohistochemical methods used by invited experts. Acta Neuropathol 2008, 116:277-288
32. Alzheimer A, Stelzmann RA, Schnitzlein HN, Murtagh FR: An English translation of Alzheimer's 1907 paper, "Uber eine eigenartige Erkankung der Hirnrinde." Clin Anat 1995, 8:429-431
33. Gregori L, Fuchs C, Figueiredo-Pereira ME, Van Nostrand WE, Goldgaber D: Amyloid beta-protein inhibits ubiquitin-dependent protein degradation in vitro. J Biol Chem 1995, 270:19702-19708
34. Gregori L, Hainfeld JF, Simon MN, Goldgaber D: Binding of amyloid beta protein to the 20 S proteasome. J Biol Chem 1997, 272:58-62 (Pubitemid 27021124)
35. Heyman A, Fillenbaum GG, Gearing M, Mirra SS, Welsh-Bohmer KA, Peterson B, Pieper C: Comparison of Lewy body variant of Alzheimer's disease with pure Alzheimer's disease: consortium to Establish a Registry for Alzheimer's Disease. Part XIX Neurology 1999, 52:1839-1844
36. Bucciantini M, Giannoni E, Chiti F, Baroni F, Formigli L, Zurdo J, Taddei N, Ramponi G, Dobson CM, Stefani M: Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature 2002, 416:507-511
37. Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S: Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 2004, 431:805-810
38. Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Cotman CW, Glabe CG: Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 2003, 300:486-489
39. Karpinar DP, Balija MB, Kugler S, Opazo F, Rezaei-Ghaleh N, Wender N, Kim HY, Taschenberger G, Falkenburger BH, Heise H, Kumar A, Riedel D, Fichtner L, Voigt A, Braus GH, Giller K, Becker S, Herzig A, Baldus M, Jackle H, Eimer S, Schulz JB, Griesinger C, Zweckstetter M: Pre-fibrillar alpha-synuclein variants with impaired beta-structure increase neurotoxicity in Parkinson's disease models. EMBO J 2009, 28:3256-3268