Ross CA, Poirier MA. (2004) Protein aggregation and neurodegenerative disease. Nat. Med. 10(Suppl):S10–7.
Dobson CM. (2004) Protein chemistry: in the footsteps of alchemists. Science 304:1259–62.
Kelly JW. (2006) Structural biology: proteins downhill all the way. Nature 442:255–6.
Alzheimer A. (1906) Über einen eigenartigen schweren Erkrankungsprozeβ der Hirnrinde. Neurologisches Zentralblatt 23:1129–36.
Ferri CP, et al. (2005) Global prevalence of dementia: a Delphi consensus study. Lancet 366:2112–7.
Evans DA, et al. (1989) Prevalence of Alzheimer’s disease in a community population of older persons: higher than previously reported. JAMA 262:2551–6.
Kukull WA, Bowen JD. (2002) Dementia epidemiology. Med. Clin. North Am. 86:573–90.
Rossor MN, Fox NC, Freeborough PA, Harvey RJ. (1996) Clinical features of sporadic and familial Alzheimer’s disease. Neurodegeneration 5:393–7.
Chai CK. (2007) The genetics of Alzheimer’s disease. Am. J. Alzheimers Dis. Other Dement. 22:37–41.
Gatz M, et al. (2006) Role of genes and environments for explaining Alzheimer disease. Arch. Gen. Psychiatry 63:168–74.
Kawas CH. (2003) Clinical practice: early Alzheimer’s disease. N. Engl. J. Med. 349:1056–63.
Nussbaum RL, Ellis CE. (2003) Alzheimer’s disease and Parkinson’s disease. N. Engl. J. Med. 348:1356–64.
de Leon MJ, et al. (2004) MRI and CSF studies in the early diagnosis of Alzheimer’s disease. J. Intern. Med. 256:205–23.
Masdeu JC, Zubieta JL, Arbizu J. (2005) Neuroimaging as a marker of the onset and progression of Alzheimer’s disease. J. Neurol. Sci. 236:55–64.
Klunk WE, et al. (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann. Neurol. 55:306–19.
Mathis CA, Klunk WE, Price JC, DeKosky ST. (2005) Imaging technology for neurodegenerative diseases: progress toward detection of specific pathologies. Arch. Neurol. 62:196–200.
Glenner GG, Wong CW. (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 120:885–90.
Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K. (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc. Natl. Acad. Sci. U. S. A. 82:4245–9.
Bentahir M, et al. (2006) Presenilin clinical mutations can affect gamma-secretase activity by different mechanisms. J. Neurochem. 96:732–42.
Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y. (1994) Visualization of Abeta 42(43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42(43). Neuron 13:45–53.
Lemere CA, Blusztajn JK, Yamaguchi H, Wisniewski T, Saido TC, Selkoe DJ. (1996) Sequence of deposition of heterogeneous amyloid beta-peptides and APO E in Down syndrome: implications for initial events in amyloid plaque formation. Neurobiol. Dis. 3:16–32.
Meda L, Baron P, Scarlato G. (2001) Glial activation in Alzheimer’s disease: the role of Abeta and its associated proteins. Neurobiol. Aging 22:885–93.
Wood JG, Mirra SS, Pollock NJ, Binder LI. (1986) Neurofibrillary tangles of Alzheimer disease share antigenic determinants with the axonal microtubule-associated protein tau (τ). Proc. Natl. Acad. Sci. U. S. A. 83:4040–3.
Kosik KS, Joachim CL, Selkoe DJ. (1986) Microtubule-associated protein tau (τ) is a major antigenic component of paired helical filaments in Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A. 83:4044–8.
Braak H, Braak E. (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 82:239–59.
Thal DR, Capetillo-Zarate E, Del Tredici K, Braak H. (2006) The development of amyloid beta protein deposits in the aged brain. Sci. Aging Knowledge Environ. 2006:re1.
Iwatsubo T, Hasegawa M, Ihara Y. (1994) Neuronal and glial tau-positive inclusions in diverse neurologic diseases share common phosphorylation characteristics. Acta Neuropathol. 88:129–36.
Gotz J, Chen F, van Dorpe J, Nitsch RM. (2001) Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 293:1491–5.
Lewis J, et al. (2001) Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 293:1487–91.
Alexander GE, Chen K, Pietrini P, Rapoport SI, Reiman EM. (2002) Longitudinal PET evaluation of cerebral metabolic decline in dementia: a potential outcome measure in Alzheimer’s disease treatment studies. Am. J. Psychiatry 159:738–45.
Park SY, Ferreira A. (2005) The generation of a 17 kDa neurotoxic fragment: an alternative mechanism by which tau mediates beta-amyloid-induced neurodegeneration. J. Neurosci. 25:5365–75.
Busciglio J, Lorenzo A, Yeh J, Yankner BA. (1995) Beta-amyloid fibrils induce tau phosphorylation and loss of microtubule binding. Neuron 14:879–88.
Greenberg SM, Koo EH, Selkoe DJ, Qiu WQ, Kosik KS. (1994) Secreted beta-amyloid precursor protein stimulates mitogen-activated protein kinase and enhances tau phosphorylation. Proc. Natl. Acad. Sci. U. S. A. 91:7104–8.
Leschik J, Welzel A, Weissmann C, Eckert A, Brandt R. (2007) Inverse and distinct modulation of tau-dependent neurodegeneration by presenilin 1 and amyloid-beta in cultured cortical neurons: evidence that tau phosphorylation is the limiting factor in amyloid-beta-induced cell death. J. Neurochem. 101:1303–15.
Roberson ED, et al. (2007) Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer’s disease mouse model. Science 316:750–4.
Haass C, et al. (1992) Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature 359:322–5.
Seubert P, et al. (1992) Isolation and quantification of soluble Alzheimer’s beta-peptide from biological fluids. Nature 359:325–7.
Shoji M, et al. (1992) Production of the Alzheimer amyloid beta protein by normal proteolytic processing. Science 258:126–9.
Cai H, Wang Y, McCarthy D, Wen H, Borchelt DR, Price DL, Wong PC. (2001) BACE1 is the major beta-secretase for generation of Abeta peptides by neurons. Nat. Neurosci. 4:233–4.
Vassar R, et al. (1999) Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286:735–41.
Schroeter EH, et al. (2003) A presenilin dimer at the core of the gamma-secretase enzyme: insights from parallel analysis of Notch 1 and APP proteolysis. Proc. Natl. Acad. Sci. U. S. A. 100:13075–80.
Mann DM, Yates PO, Marcyniuk B. (1984) Alzheimer’s presenile dementia, senile dementia of Alzheimer type and Down’s syndrome in middle age form an age related continuum of pathological changes. Neuropathol. Appl. Neurobiol. 10:185–207.
Olson MI, Shaw CM. (1969) Presenile dementia and Alzheimer’s disease in mongolism. Brain 92:147–56.
Prasher VP, Farrer MJ, Kessling AM, Fisher EM, West RJ, Barber PC, Butler AC. (1998) Molecular mapping of Alzheimer-type dementia in Down’s syndrome. Ann. Neurol. 43:380–3.
Busciglio J, Lorenzo A, Yankner BA. (1992) Methodological variables in the assessment of beta amyloid neurotoxicity. Neurobiol. Aging 13:609–12.
Pike CJ, Walencewicz AJ, Glabe CG, Cotman CW. (1991) In vitro aging of beta-amyloid protein causes peptide aggregation and neurotoxicity. Brain Res. 563:311–4.
Pike CJ, Burdick D, Walencewicz AJ, Glabe CG, Cotman CW. (1993) Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state. J. Neurosci. 13:1676–87.
Chartier-Harlin MC, et al. (1991) Early-onset Alzheimer’s disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene. Nature 353:844–6.
Citron M, et al. (1992) Mutation of the beta-amyloid precursor protein in familial Alzheimer’s disease increases beta-protein production. Nature 360:672–4.
Goate A, et al. (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349:704–6.
Levy E, et al. (1990) Mutation of the Alzheimer’s disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science 248:1124–6.
Kumar-Singh S, et al. (2006) Mean age-of-onset of familial Alzheimer disease caused by presenilin mutations correlates with both increased Abeta42 and decreased Abeta40. Hum. Mutat. 27:686–95.
Corder EH, et al. (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261:921–3.
Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD. (1993) Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A. 90:1977–81.
Games D, Buttini M, Kobayashi D, Schenk D, Seubert P. (2006) Mice as models: transgenic approaches and Alzheimer’s disease. J. Alzheimers Dis. 9:133–49.
Vigo-Pelfrey C, Lee D, Keim P, Lieberburg I, Schenk DB. (1993) Characterization of beta-amyloid peptide from human cerebrospinal fluid. J. Neurochem. 61:1965–8.
Walsh DM, Tseng BP, Rydel RE, Podlisny MB, Selkoe DJ. (2000) The oligomerization of amyloid beta-protein begins intracellularly in cells derived from human brain. Biochemistry 39:10831–9.
Deshpande A, Mina E, Glabe C, Busciglio J. (2006) Different conformations of amyloid beta induce neurotoxicity by distinct mechanisms in human cortical neurons. J. Neurosci. 26:6011–8.
Terry RD, et al. (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 30:572–80.
Lue LF, et al. (1999) Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer’s disease. Am. J. Pathol. 155:853–62.
McLean CA, et al. (1999) Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer’s disease. Ann. Neurol. 46:860–6.
Morishima-Kawashima M, Ihara Y. (1998) The presence of amyloid beta-protein in the detergent-insoluble membrane compartment of human neuroblastoma cells. Biochemistry 37:15247–53.
Georganopoulou DG, Chang L, Nam JM, Thaxton CS, Mufson EJ, Klein WL, Mirkin CA. (2005) Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer’s disease. Proc. Natl. Acad. Sci. U. S. A. 102:2273–6.
Enya M, et al. (1999) Appearance of sodium dodecyl sulfate-stable amyloid beta-protein (Abeta) dimer in the cortex during aging. Am. J. Pathol. 154:271–9.
Podlisny MB, Ostaszewski BL, Squazzo SL, Koo EH, Rydell RE, Teplow DB, Selkoe DJ. (1995) Aggregation of secreted amyloid beta-protein into sodium dodecyl sulfate-stable oligomers in cell culture. J. Biol. Chem. 270:9564–70.
Walsh DM, Klyubin I, Fadeeva JV, Rowan MJ, Selkoe DJ. (2002) Amyloid-beta oligomers: their production, toxicity and therapeutic inhibition. Biochem. Soc. Trans. 30:552–7.
Walsh DM, et al. (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416:535–9.
Wang Q, Walsh DM, Rowan MJ, Selkoe DJ, Anwyl R. (2004) Block of long-term potentiation by naturally secreted and synthetic amyloid beta-peptide in hippocampal slices is mediated via activation of the kinases c-Jun N-terminal kinase, cyclin-dependent kinase 5, and p38 mitogen-activated protein kinase as well as metabotropic glutamate receptor type 5. J. Neurosci. 24:3370–8.
Cleary JP, Walsh DM, Hofmeister JJ, Shankar GM, Kuskowski MA, Selkoe DJ, Ashe KH. (2005) Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat. Neurosci. 8:79–84.
Calabrese B, Shaked GM, Tabarean IV, Braga J, Koo EH, Halpain S. (2007) Rapid, concurrent alterations in pre- and postsynaptic structure induced by naturally-secreted amyloid-beta protein. Mol. Cell Neurosci. 35:183–93.
Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL. (2007) Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J. Neurosci. 27:2866–75.
Harper JD, Lieber CM, Lansbury PT Jr. (1997) Atomic force microscopic imaging of seeded fibril formation and fibril branching by the Alzheimer’s disease amyloid-beta protein. Chem. Biol. 4:951–9.
Walsh DM, Lomakin A, Benedek GB, Condron MM, Teplow DB. (1997) Amyloid beta-protein fibrillogenesis: detection of a protofibrillar intermediate. J. Biol. Chem. 272:22364–72.
Walsh DM, et al. (1999) Amyloid beta-protein fibrillogenesis: structure and biological activity of protofibrillar intermediates. J. Biol. Chem. 274:25945–52.
Hartley DM, et al. (1999) Protofibrillar intermediates of amyloid beta-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J. Neurosci. 19:8876–84.
Lambert MP, et al. (1998) Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc. Natl. Acad. Sci. U. S. A. 95:6448–53.
Wang HW, et al. (2002) Soluble oligomers of beta amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus. Brain Res. 924:133–40.
Lacor PN, et al. (2004) Synaptic targeting by Alzheimer’s-related amyloid beta oligomers. J. Neurosci. 24:10191–200.
Lacor PN, et al. (2007) Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer’s disease. J. Neurosci. 27:796–807.
Schenk D, et al. (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400:173–7.
Gilman S, et al. (2005) Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology 64:1553–62.
Andreasen N, et al. (1999) Cerebrospinal fluid beta-amyloid(1–42) in Alzheimer disease: differences between early- and late-onset Alzheimer disease and stability during the course of disease. Arch. Neurol. 56:673–80.
Fagan AM, et al. (2006) Inverse relation between in vivo amyloid imaging load and cerebrospinal fluid Abeta42 in humans. Ann. Neurol. 59:512–9.
Irizarry MC. (2004) Biomarkers of Alzheimer disease in plasma. NeuroRx 1:226–34.
Kahle PJ, et al. (2000) Combined assessment of tau and neuronal thread protein in Alzheimer’s disease CSF. Neurology 54:1498–504.
Buerger K, et al. (2002) Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231. Arch. Neurol. 59:1267–72.
Blennow K. (2004) Cerebrospinal fluid protein biomarkers for Alzheimer’s disease. NeuroRx 1:213–25.
Riemenschneider M, et al. (2002) Tau and Abeta42 protein in CSF of patients with frontotemporal degeneration. Neurology 58:1622–8.
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. 43:155–60.
Hansson O, Zetterberg H, Buchhave P, Andreasson U, Londos E, Minthon L, Blennow K. (2007) Prediction of Alzheimer’s disease using the CSF Abeta42/Abeta40 ratio in patients with mild cognitive impairment. Dement. Geriatr. Cogn. Disord. 23:316–20.
Herukka SK, Hallikainen M, Soininen H, Pirttila T. (2005) CSF Abeta42 and tau or phosphorylated tau and prediction of progressive mild cognitive impairment. Neurology 64:1294–7.
Pitschke M, Prior R, Haupt M, Riesner D. (1998) Detection of single amyloid beta-protein aggregates in the cerebrospinal fluid of Alzheimer’s patients by fluorescence correlation spectroscopy. Nat. Med. 4:832–4.
Parkinson J. (2002) An essay on the shaking palsy. 1817. J. Neuropsychiatry Clin. Neurosci. 14:223–36.
de Rijk MC, et al. (2000) Prevalence of Parkinson’s disease in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 54:S21–3.
Shults CW. (2006) Lewy bodies. Proc. Natl. Acad. Sci. U. S. A. 103:1661–8.
Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M. (1998) alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies. Proc. Natl. Acad. Sci. U. S. A. 95:6469–73.
Crowther RA, Jakes R, Spillantini MG, Goedert M. (1998) Synthetic filaments assembled from C-terminally truncated alpha-synuclein. FEBS Lett. 436:309–12.
Braak H, Rub U, Gai WP, Del Tredici K. (2003) Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J. Neural Transm. 110:517–36.
Jenner P. (1989) Clues to the mechanism underlying dopamine cell death in Parkinson’s disease. J. Neurol. Neurosurg. Psychiatry Suppl:22–8.
Turnbull S, Tabner BJ, El-Agnaf OM, Moore S, Davies Y, Allsop D. (2001) alpha-Synuclein implicated in Parkinson’s disease catalyses the formation of hydrogen peroxide in vitro. Free Radic. Biol. Med. 30:1163–70.
Langston JW, Ballard P, Tetrud JW, Irwin I. (1983) Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219:979–80.
Ramsay RR, Salach JI, Dadgar J, Singer TP. (1986) Inhibition of mitochondrial NADH dehydrogenase by pyridine derivatives and its possible relation to experimental and idiopathic parkinsonism. Biochem. Biophys. Res. Commun. 135:269–75.
Dauer W, Przedborski S. (2003) Parkinson’s disease: mechanisms and models. Neuron 39:889–909.
Polymeropoulos MH, et al. (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276:2045–7.
Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. (1997) Alpha-synuclein in Lewy bodies. Nature 388:839–40.
Kruger R, et al. (1998) Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson’s disease. Nat. Genet. 18:106–8.
Zarranz JJ, et al. (2004) The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann. Neurol. 55:164–73.
George JM, Jin H, Woods WS, Clayton DF. (1995) Characterization of a novel protein regulated during the critical period for song learning in the zebra finch. Neuron 15:361–72.
Bodles AM, Guthrie DJ, Greer B, Irvine GB. (2001) Identification of the region of non-Abeta component (NAC) of Alzheimer’s disease amyloid responsible for its aggregation and toxicity. J. Neurochem. 78:384–95.
Park SM, Jung HY, Kim TD, Park JH, Yang CH, Kim J. (2002) Distinct roles of the N-terminal-binding domain and the C-terminal-solubilizing domain of alpha-synuclein, a molecular chaper-one. J. Biol. Chem. 277:28512–20.
Chandra S, et al. (2004) Double-knockout mice for alpha- and beta-synucleins: effect on synaptic functions. Proc. Natl. Acad. Sci. U. S. A. 101:14966–71.
Bussell R Jr, Eliezer D. (2003) Astructural and functional role for 11-mer repeats in alpha-synuclein and other exchangeable lipid binding proteins. J. Mol. Biol. 329:763–78.
Larsen KE, et al. (2006) Alpha-synuclein overexpression in PC12 and chromaffin cells impairs catecholamine release by interfering with a late step in exocytosis. J. Neurosci. 26:11915–22.
Chandra S, Gallardo G, Fernandez-Chacon R, Schluter OM, Sudhof TC. (2005) Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration. Cell 123:383–96.
El-Agnaf OM, Jakes R, Curran MD, Wallace A. (1998) Effects of the mutations Ala30 to Pro and Ala53 to Thr on the physical and morphological properties of alpha-synuclein protein implicated in Parkinson’s disease. FEBS Lett. 440:67–70.
Greenbaum EA, et al. (2005) The E46K mutation in alpha-synuclein increases amyloid fibril formation. J. Biol. Chem. 280:7800–7.
Chartier-Harlin MC, et al. (2004) Alpha-synuclein locus duplication as a cause of familial Parkinson’s disease. Lancet 364:1167–9.
Ibanez P, et al. (2004) Causal relation between alpha-synuclein gene duplication and familial Parkinson’s disease. Lancet 364:1169–71.
Singleton AB, et al. (2003) alpha-Synuclein locus triplication causes Parkinson’s disease. Science 302:841.
Anderson JP, et al. (2006) Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J. Biol. Chem. 281:29739–52.
Fujiwara H, et al. (2002) alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat. Cell Biol. 4:160–4.
Giasson BI, et al. (2000) Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 290:985–9.
Yamin G, Uversky VN, Fink AL. (2003) Nitration inhibits fibrillation of human alpha-synuclein in vitro by formation of soluble oligomers. FEBS Lett. 542:147–52.
Conway KA, Rochet JC, Bieganski RM, Lansbury PT Jr. (2001) Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Science 294:1346–9.
Mazzulli JR, Armakola M, Dumoulin M, Parastatidis I, Ischiropoulos H. (2007) Cellular oligomerization of alpha-synuclein is determined by the interaction of oxidized catechols with a C-terminal sequence. J. Biol. Chem. 282:31621–30.
Sharon R, Bar-Joseph I, Frosch MP, Walsh DM, Hamilton JA, Selkoe DJ. (2003) The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson’s disease. Neuron 37:583–95.
Uversky VN, Li J, Bower K, Fink AL. (2002) Synergistic effects of pesticides and metals on the fibrillation of alpha-synuclein: implications for Parkinson’s disease. Neurotoxicology 23:527–36.
Manning-Bog AB, McCormack AL, Li J, Uversky VN, Fink AL, Di Monte DA. (2002) The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein. J. Biol. Chem. 277:1641–4.
Zecca L, Youdim MB, Riederer P, Connor JR, Crichton RR. (2004) Iron, brain ageing and neurodegenerative disorders. Nat. Rev. Neurosci. 5:863–73.
El-Agnaf OM, et al. (1998) Aggregates from mutant and wild-type alpha-synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of beta-sheet and amyloid-like filaments. FEBS Lett. 440:71–5.
Volles MJ, Lansbury PT Jr. (2003) Zeroing in on the pathogenic form of alpha-synuclein and its mechanism of neurotoxicity in Parkinson’s disease. Biochemistry 42:7871–8.
Smith DP, Tew DJ, Hill AF, Bottomley SP, Masters CL, Barnham KJ, Cappai R. (2008) Formation of a high affinity lipid-binding intermediate during the early aggregation phase of alpha-synuclein. Biochemistry 47:1425–34.
Feany MB, Bender WW. (2000) A Drosophila model of Parkinson’s disease. Nature 404:394–8.
Masliah E, et al. (2000) Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 287:1265–9.
Klivenyi P, et al. (2006) Mice lacking alpha-synuclein are resistant to mitochondrial toxins. Neurobiol. Dis. 21:541–8.
Cookson MR, van der Brug M. (2007) Cell systems and the toxic mechanism(s) of alpha-synuclein. Exp. Neurol. 209:5–11.
Greene JC, Whitworth AJ, Andrews LA, Parker TJ, Pallanck LJ. (2005) Genetic and genomic studies of Drosophila parkin mutants implicate oxidative stress and innate immune responses in pathogenesis. Hum. Mol. Genet. 14:799–811.
Palacino JJ, et al. (2004) Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J. Biol. Chem. 279:18614–22.
Valente EM, et al. (2004) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304:1158–60.
Canet-Aviles RM, et al. (2004) The Parkinson’s disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proc. Natl. Acad. Sci. U. S. A. 101:9103–8.
Zhou W, Zhu M, Wilson MA, Petsko GA, Fink AL. (2006) The oxidation state of DJ-1 regulates its chaperone activity toward alpha-synuclein. J. Mol. Biol. 356:1036–48.
Zimprich A, et al. (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44:601–7.
Sulzer D. (2007) Multiple hit hypotheses for dopamine neuron loss in Parkinson’s disease. Trends Neurosci. 30:244–50.
Rueger MA, et al. (2007) Role of in vivo imaging of the central nervous system for developing novel drugs. Q. J. Nucl. Med. Mol. Imaging 51:164–81.
Hughes AJ, Ben-Shlomo Y, Daniel SE, Lees AJ. (1992) What features improve the accuracy of clinical diagnosis in Parkinson’s disease: a clinicopathologic study. Neurology 42:1142–6.
Ye L, et al. (2008) In vitro high affinity alpha-synuclein binding sites for the amyloid imaging agent PIB are not matched by binding to Lewy bodies in postmortem human brain. J. Neurochem. 2008, Feb 18 [Epub ahead of print]
Scherzer CR, et al. (2007) Molecular markers of early Parkinson’s disease based on gene expression in blood. Proc. Natl. Acad. Sci. U. S. A. 104:955–60.
Bogdanov M, Matson WR, Wang L, Matson T, Saunders-Pullman R, Bressman SS, Flint Beal M. (2008) Metabolomic profiling to develop blood biomarkers for Parkinson’s disease. Brain 131:389–96.
Wolozin B, Wang SW, Li NC, Lee A, Lee TA, Kazis LE. (2007) Simvastatin is associated with a reduced incidence of dementia and Parkinson’s disease. BMC Med. 5:20.
Bodles AM, El-Agnaf OM, Greer B, Guthrie DJ, Irvine GB. (2004) Inhibition of fibril formation and toxicity of a fragment of alpha-synuclein by an N-methylated peptide analogue. Neurosci. Lett. 359:89–93.
Amer DA, Irvine GB, El-Agnaf OM. (2006) Inhibitors of alpha-synuclein oligomerization and toxicity: a future therapeutic strategy for Parkinson’s disease and related disorders. Exp. Brain Res. 173:223–33.
Zhu M, Rajamani S, Kaylor J, Han S, Zhou F, Fink AL. (2004) The flavonoid baicalein inhibits fibrillation of alpha-synuclein and disaggregates existing fibrils. J. Biol. Chem. 279:26846–57.
Masliah E, et al. (2005) Effects of alpha-synuclein immunization in a mouse model of Parkinson’s disease. Neuron 46:857–68.