Abnormal interactions and misfolding of synaptic proteins in the nervous system are being extensively explored as important pathogenic events resulting in neurodegeneration in various neurological disorders. These include Alzheimer’s disease (AD), Parkinson’s disease (PD), and dementia with Lewy bodies (DLB). In AD, misfolded amyloid β peptide 1–42 (Aβ), a proteolytic product of amyloid precursor protein metabolism, accumulates in the neuronal endoplasmic reticulum and extracellularly as plaques. In contrast, in PD and DLB cases there is abnormal accumulation of α-synuclein in neuronal cell bodies, axons, and synapses. Furthermore, in DLB, Aβ 1–42 may promote α-synuclein accumulation and neurodegeneration. The central event leading to synaptic and neuronal loss in these diseases is not completely clear yet; however, recent advances in the field suggest that nerve damage might result from the conversion of nontoxic monomers to toxic oligomers and protofibrils. The mechanisms by which misfolded Aβ peptide and α-synuclein might lead to synapse loss are currently under investigation. Several lines of evidence support the possibility that Aβ peptide and α-synuclein might interact to cause mitochondrial and plasma membrane damage upon translocation of protofibrils to the membranes. Accumulation of Aβ and α-synuclein oligomers in the mitochondrial membrane might result in the release of cytochrome C with the subsequent activation of the apoptosis cascade. Conversely, the oxidative stress and mitochondrial dysfunction associated with AD and PD may also lead to increased membrane permeability and cytochrome C release, which promotes Aβ and α-synuclein oligomerization and neurodegeneration. Together, these studies suggest that the translocation of misfolded proteins to the mitochondrial membrane might play an important role in either triggering or perpetuating neurodegeneration. The insights obtained from the characterization of this process may be applied to the role of mitochondrial dysfunction in other neurodegenerative disorders, including AD. New evidence may also provide a rationale for the mitochondrial membrane as a target for therapy in a variety of neurodegenerative diseases.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Alves Da Costa C., Ancolio K., and Checler F. (2000) Wild-type but not Parkinson’s disease-related ala-53→Thr mutant alpha synuclein protects neuronal cells from apoptotic stimuli. J. Biol. Chem. 275, 24065–24069.
Askanas V., McFerrin J., Baque S., et al. (1996) Transfer of β-amyloid precursor protein gene using adenovirus vector causes mitochondrial abnormalities in cultures of normal human muscle. Proc. Natl. Acad. Sci. USA 93, 1314–1319.
Avila J., Lim, F., Moreno F. et al. (2002) Tau function and dysfunction in neurons: its role in neuro-degenerative disorders. Mol. Neurobiol. 25, 213–231.
Betarbet R., Sherer T. B., MacKenzie G., et al. (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat. Neurosci. 3, 1301–1306.
Bonifati V., Rizzu P., van Baren M. J., et al. (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299, 256–259.
Busciglio J., Pelsman A., Wong C., et al. (2002) Altered metabolism of the amyloid beta precursor protein is associated with mitochondrial dysfunction in Down’s syndrome. Neuron 33, 677–688.
Bush A. I. (2002) Metal complexing agents as therapies for Alzheimer’s disease. Neurobiol. Aging 23, 1031–1038.
Chan S. L., Furukawa K., and Mattson M. P. (2002) Presenilins and APP in neuritic and synaptic plasticity: implications for the pathogenesis of Alzheimer’s disease. Neuromol. Med. 2, 167–196.
Chartier-Harlin M.-C., Crawford F., Houlden H., et al. (1991) Early-onset Alzheimer’s disease caused by mutations at codon 717 of the β-amyloid precursor protein gene. Nature 353, 844–846.
Conway K., Harper J., and Lansbury P. (1998) Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease. Nat. Med. 4, 1318–1320.
Conway K. A., Lee S. J., Rochet J. C., et al. (2000) Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson’s disease: implications for pathogenesis and therapy. Proc. Natl. Acad. Sci. USA 97, 571–576.
Cummings C. J. and Zoghbi H. Y. (2000) Trinucleotide repeats: mechanisms and pathophysiology. Annu. Rev. Genomics Hum. Genet. 1, 281–328.
Dauer W., Kholodilov N., Vila M., et al. (2002) Resistance of alpha-synuclein null mice to the parkinsonian neurotoxin MPTP. Proc. Natl. Acad. Sci. USA 99, 14524–14529.
Duff K., Eckman C., Zehr C., et al. (1996) Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature 383, 710–713.
Feany M. and Bender W. (2000) A Drosophila model of Parkinson’s disease. Nature 404, 394–398.
Ferrigno P. and Silver P. (2000) Polyglutamine expansions: proteolysis, chaperones, and the dangers of promiscuity. Neuron 26, 9–12.
Fujiwara H., Hasegawa M., Dohmae N., et al. (2002) alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat. Cell Biol. 4, 160–164.
Gearing M., Mirra S., Hedreen J., et al. (1995) Neuropathology confirmation of the clinical diagnosis of Alzheimer’s disease: CERAD. Part X. Neurology 45, 461–466.
Giasson B. I., Duda J. E., Murray I. V., et al. (2000) Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 290, 985–989.
Goate A., Chartier-Harlin M.-C., Mullan M., et al. (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer’s disease. Nature 349, 704.
Good P. F., Werner P., Hsu A., Olanow C. W., and Perl D. P. (1996) Evidence of neuronal oxidative damage in Alzheimer’s disease. Am. J. Pathol. 149, 21–28.
Gosavi N., Lee H. J., Lee J. S., Patel S., and Lee S. J. (2002) Golgi fragmentation occurs in the cells with prefibrillar alpha-synuclein aggregates and precedes the formation of fibrillar inclusion. J. Biol. Chem. 277, 48984–48992.
Haas C., Hung A. Y., Citron M., Teplow D. B., and Selkoe D. J. (1995) beta-Amyloid, protein processing and Alzheimer’s disease. Arzneimittelforschung 45, 398–402.
Hashimoto M., and Masliah E. (1999) Alpha-synuclein in Lewy body disease and Alzheimer’s disease. Brain Pathol. 9, 707–720.
Hashimoto M., Takeda A., Hsu L. J., Takenouchi T., and Masliah E. (1999a) Role of cytochrome c as a stimulator of α-synuclein aggregation in Lewy body disease. J. Biol. Chem. 274, 28849–28852.
Hashimoto M., Hsu L., Xia Y., et al. (1999b) Oxidative stress induces amyloid-like aggregate formation of NACP/α-synuclein in vitro. Neuroreport 10, 717–721.
Hashimoto M., Hernandez-Ruiz S., Hsu L., et al. (1998) Human recombinant NACP/a-synuclein is aggregated and fibrillated in vitro: Relevance for Lewy body disease. Brain Res 799, 301–306
Hensley K., Carney J. M., Mattson M. P., et al. (1994) A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc. Natl. Acad. Sci. USA 91, 3270–3274.
Hod Y., Pentyala S. N., Whyard T. C., and El-Maghrabi M. R. (1999) Identification and characterization of a novel protein that regulates RNA-protein interaction. J. Cell Biochem. 72, 435–444.
Hsu L. J., Sagara Y., Arroyo A., et al. (2000) α-Synuclein promotes mitochondrial deficiencies and oxidative stress. Am. J. Pathol. 157, 401–410.
Imai Y., Soda M., Inoue H., et al. (2001) An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell 105, 891–902.
Irizarry M., Growdon W., Gomez-Isla T., et al. (1998) Nigral and cortical Lewy bodies and dystrophic nigral neurites in Parkinson’s disease and cortical Lewy body disease contain alpha-synuclein immunoreactivity. J. Neuropathol. Exp. Neurol. 57, 334–337.
Iwai A. (2000) Properties of NACP/alpha-synuclein and its role in Alzheimer’s disease. Biochim. Biophys. Acta 1502, 95–109.
Iwai A., Masliah E., Yoshimoto M., et al. (1994) The precursor protein of non-Ab component of Alzheimer’s disease amyloid (NACP) is a presynaptic protein of the central nervous system. Neuron 14, 467–475.
Jakes R., Spillantini M., and Goedert M. (1994) Identification of two distinct synucleins from human brain. FEBS Lett. 345, 27–32.
Jenner P. (1998) Oxidative mechanisms in nigral cell death in Parkinson’s disease. Mov. Disord. 13, 24–34.
Jia T., Liu Y. E., Liu J., and Shi Y. E. (1999) Stimulation of breast cancer invasion and metastasis by synuclein gamma. Cancer Res. 59, 742–747.
Jo E., McLaurin J., Yip C., St. George-Hyslop P., and Graser P. (2000) Alpha-synuclein membrane iteractions and lipid specificity. J. Biol. Chem. 275, 34328–34334.
Keller J. N., Kindy M. S., Holtsberg F. W., et al. (1998) Mitochondrial manganese superoxide dismutase prevents neural apoptosis and reduces ischemic brain injury: suppression of peroxynitrite production, lipid peroxidation, and mitochondrial dysfunction. J. Neurosci. 18, 687–697
Keller J. N., Pang Z., Geddes J. W., et al. (1997) Impairment of glucose and glutamate transport and induction of mitochondrial oxidative stress and dysfunction in synaptosomes by amyloid beta-peptide: role of the lipid peroxidation product 4-hydroxynonenal. J. Neurochem.
Kirschenbaum F., Hsu S. C., Cordell B., and McCarthy J. V. (2001) Glycogen synthase kinase-3beta regulates presenilin 1 C-terminal fragment levels. J. Biol. Chem. 276, 30701–30707.
Kish S. J., Bergeron C., Rajput A., et al. (1992) Brain cytochrome oxidase in Alzheimer’s disease. J. Neurochem. 59,, 776–779.
Kitada T., Asakawa S., Hattori N., et al. (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392, 605–608.
Klein R. L., King M. A., Hamby M. E., and Meyer E. M. (2002) Dopaminergic cell loss induced by human A30P alpha-synuclein gene transfer to the rat substantia nigra. Hum. Gene Ther. 13, 605–612.
Koo E., Lansbury P. J., and Kelly J. (1999) Amyloid diseases: abnormal protein aggregation in neurodegeneration. Proc. Natl. Acad. Sci. USA 96, 9989–9990.
Kruger R., Kuhn W., Muller T., et al. (1998) Ala30Pro mutation in the gene encoding α-synuclein in Parkinson’s disease. Nat. Genet. 18, 106–108.
Langston J. W., Langston E. B., and Irwin I. (1984a) MPTP-induced parkinsonism in human and nonhuman primates—clinical and experimental aspects. Acta. Neurol. Scand. Suppl. 100, 49–54.
Langston J. W., Forno L. S., Rebert C. S., and Irwin I. (1984b) Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyrine (MPTP) in the squirrel monkey. Brain Res. 292, 390–394.
Lansbury P. T. J. (1999) Evolution of amyloid: what normal protein folding may tell us about fibrillogenesis and disease. Proc. Natl. Acad. Sci. USA 96, 3342–3344.
Lee H. J., Shin S. Y., Choi C., Lee Y. H., and Lee S. J. (2002) Formation and removal of alpha-synuclein aggregates in cells exposed to mitochondrial inhibitors. J. Biol. Chem. 277, 5411–5417.
Leroy E., Boyer R., Auburger G., et al. (1998) The ubiquitin pathway in Parkinsons’s disease. Nature 395, 451–452.
Liu Y., Fallon L., Lashuel H. A., Liu Z., and Lansbury P. T. J. (2002) The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson’s disease susceptibility. Cell 111, 209–218.
Manning-Bog A. B., McCormack A. L., Purisai M. G., Bolin L. M., and Di Monte D. A. (2003) Alpha-synuclein overexpression protects against paraquat-induced neurodegeneration. J. Neurosci. 23, 3095–3099.
Masliah E. (2001) Recent advances in the understanding of the role of synaptic proteins in Alzheimer’s disease and other neurodegenerative disorders. IJ. Alz. Dis. 3, 1–9.
Masliah E. (2000) The role of synaptic proteins in Alzheimer’s disease. Ann. NY Acad. Sci. 924, 68–75.
Masliah E., Rockenstein E., Veinbergs I., et al. (2000) Dopaminergic loss and inclusion body formation in alpha-synuclein mice: Implications for neurodegenerative disorders. Science 287, 1265–1269.
Masliah E., Iwai A., Mallory M., Ueda K., Saitoh T (1996) Altered presynaptic protein NACP is associated with plaque formation and neurodegeneration in Alzheimer’s disease. Am. J. Pathol. 148, 201–210.
Masliah E., Rockenstein E., Veinbergs I., et al. (2001) β amyloid peptides enhance α-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer’s and Parkinson’s disease. Proc. Natl. Acad. Sci. USA 98, 12245–12250.
Mitsumoto A., Nakagawa Y., Takeuchi A., et al. (2001) Oxidized forms of peroxiredoxins and DJ-1 on two-dimensional gels increased in response to sublethal levels of paraquat. Free Radic. Res. 35, 301–310.
Mizuno Y., Ikebe S., Hattori N., et al. (1995) Role of mitochondria in the etiology and pathogenesis of Parkinson’s disease. Biochim. Biophys. Acta. 1271, 265–274.
Muchowski P. J. (2002) Protein misfolding, amyloid formation, and neurodegeneration: a critical role for molecular chaperones? Neuron 35, 9–12.
Nagakubo D., Taira T., Kitaura H., et al. (1997) DJ-1, a novel oncogene which transforms mouse NIH3T3 cells in cooperation with ras. Biochem. Biophys. Res. Commun. 231, 509–513.
Nakajo S., Tsukada K., Omata K., Nakamura Y., and Nakaya K. (1993) A new brain-specific 14-kDa protein is a phosphoprotein. Its complete amino acid sequence and evidence for phosphorylation. Eur. J. Biochem. 217, 1057–1063.
Narayanan V. and Scarlata S. (2001) Membrane binding and self-association of alpha-synucleins. Biochemistry 40, 9927–9934.
Negro A., Brunati A. M., Donella-Deana A., Massimino M. L., and Pinna L. A. (2002) Multiple phosphorylation of alpha-synuclein by protein tyrosine kinase Syk prevents eosin-induced aggregation. FASEB J. 16, 210–212.
Orth M. and Schapira A. H. (2001) Mitochondria and degenerative disorders. Am. J. Med. Genet. 106, 27–36.
Osterova-Golts N., Petrucelli L., Hardy J., et al. (2000) The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity. J. Neurosci. 20, 6048–6054.
Ostrerova N., Petrucelli L., Farrer M., et al. (1999) alpha-synuclein shares physical and functional homology with 14-3-3 proteins. J. Neurosci. 19, 5782–5791.
Paik S. R., Shin H. J., Lee J. H., Chang C. S., and Kim J. (1999) Copper(II)-induced self-oligomerization of alpha-synuclein. Biochem. J. 340, 821–828.
Parker W. D. J., Filley C. M., and Parks J. K. (1990) Cytochrome oxidase deficiency in Alzheimer’s disease. Neurology 40, 1302–1303.
Perrin R., Woods W., Clayton D., and George J. (2000) Interaction of human alpha-synuclein and Parkinson’s disease variants with phospholipids: structural analysis using site-directed mutagenesis. J. Biol. Chem. 275, 34393–34398.
Petrucelli L., O’Farrell C., Lockhart P. J., et al. (2002) Parkin protects against the toxicity associated with mutant alpha-synuclein: proteasome dysfunction selectively affects catecholaminergic neurons. Neuron 36, 1007–1019.
Pfanner N. and Meijer M (1997) The Tom and Tim machine. Curr. Biol. 7, 100–103.
Polymeropoulos M., Lavedan C., Leroy E., et al. (1997) Mutation in the α-synuclein gene identified in families with Parkinson’s disease. Science 276, 2045–2047.
Ramassamy C., Averill D., Beffert U., et al. (1999) Oxidative damage and protection by antioxidants in the frontal cortex of Alzheimer’s disease is related to the apolipoprotein E genotype. Free Radic. Biol. Med. 27, 544–553.
Rochet J., Conway K., and Lansbury P. J. (2000) Inhibition of fibrillization and accumulation of prefibrillar oligomers in mixtures of human and mouse α-synuclein. Biochemistry 39, 10619–10626.
Rockenstein E., Mallory M., Hashimoto M., et al. (2002) Differential neuropathological alterations in transgenic mice expressing α-synuclein from the platelet-derived growth factor and Thy-1 promoters. J. Neurosci. Res. 68, 568–578.
Schapira A. H., Gu M., Taanman J. W., et al. (1998) Mitochondria in the etiology and pathogenesis of Parkinson’s disease. Ann. Neurol. 44, S89–98.
Selkoe D. J., Yamazaki T., Citron M., et al. (1996) The role of APP processing and trafficking pathways in the formation of amyloid beta-protein. Ann. NY Acad. Sci. 777, 57–64.
Serpell L., Berriman J., Jakes R., Goedert M., and Crowther R. (2000) Fiber diffraction of synthetic α-synuclein filaments shows amyloid-like cross-β conformation. Proc. Natl. Acad. Sci. USA 97, 4897–4902.
Sherer T. B., Kim J. H., Betarbet R., and Greenamyre J. T. (2003) Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and alpha-synuclein aggregation. Exp. Neurol. 179, 9–16.
Shigenaga M., Hagen T., and Ames B. (1994) Oxidative damage and mitochondrial decay in aging. Proc. Natl. Acad. Sci. USA 91, 10771–10778.
Shimura H., Hattori N., Kubo S.-I., et al. (2000) Familialr Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat. Genet. 25, 302–305.
Smith M. A., Perry G., Richey P. L., et al. (1996) Oxidative damage in Alzheimer’s. Nature 382, 120–121.
Song D., Shults C., Sisk A., Rockenstein E., and Masliah E. (2003) Enhanced Sustantia Nigra Pathology in human α-synuclein Transgenic Mice after treatment with MPTP. Exp. Neurol., in press.
Souza J., Giasson B., Chen Q., Lee V.-Y., and Ischiropoulos H. (2000) Dityrosine cross-linking promotes formation of stable alpha-synuclein polymers. J. Biol. Chem. 275, 18344–18349.
Spillantini M., Schmidt M., Lee V.-Y., et al. (1997) α-Synuclein in Lewy bodies. Nature 388, 839–840.
Surguchov A., Surgucheva I., Solessio E., and Baehr W. (1999) Synoretin—A new protein belonging to the synuclein family. Mol. Cell Neurosci. 13, 95–103.
Swerdlow R. H., Parks J. K., Cassarino D. S., et al. (1997) Cybrids in Alzheimer’s disease: a cellular model of the disease? Neurology 49, 918–925.
Takeda A., Mallory M., Sundsmo M., et al. (1998a) Abnormal accumulation of NACP / α-synuclein in neurodegenerative disorders. Am. J. Pathol. 152, 367–372.
Takeda A., Hashimoto M., Mallory M., et al. (1998b) Abnormal distribution of the non-Ab component of Alzheimer’s disease amyloid precursor/α-synuclein in Lewy body disease as revealed by proteinase K and formic acid pretreatment. Lab. Invest. 78, 1169–1177.
Tanaka Y., Engelender S., Igarashi S., et al. (2001) Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis. Hum. Mol. Genet. 10, 919–926.
Terry R., Hansen L., and Masliah E. (1994) Structural basis of the cognitive alterations in Alzheimer disease. In: Alzheimer Disease (Terry R., Katzman R., eds.), Raven Press, New York, pp. 179–196.
Trojanowski J. and Lee V. (1998) Aggregation of neurofilament and alpha-synuclein proteins in Lewy bodies: implications for pathogenesis of Parkinson disease and Lewy body dementia. Arch. Neurol. 55, 151–152.
Trojanowski J., Goedert M., Iwatsubo T., and Lee V. (1998) Fatal attractions: abnormal protein aggregation and neuron death in Parkinson’s disease and lewy body dementia. Cell Death Differ. 5, 832–837.
Trojanowski J. Q. and Lee V. M. (2000) “Fatal attractions” of proteins. A comprehensive hypothetical mechanism underlying Alzheimer’s disease and other neurodegenerative disorders. Ann. N Y Acad. Sci. 924, 62–67.
Ueda K., Masliah E., Xia Y., et al. (1993) Novel amyloid component (NAC) differentiates Alzheimer’s disease from normal aging plaques. Soc. Neurosci. Abstr. 19, 1254.
Volles M. J. and Lansbury P. T., Jr. (2002) Vesicle permeabilization by protofibrillar alpha-synuclein is sensitive to Parkinson’s disease-linked mutations and occurs by a pore-like mechanism. Biochemistry 41, 4595–4602.
Volles M. J., Lee S. J., Rochet J. C., et al. (2001) Vesicle permeabilization by protofibrillar alpha-synuclein: implications for the pathogenesis and treatment of Parkinson’s disease. Biochemistry 40, 7812–7819.
Wagenfeld A., Gromoll J., and Cooper T. G. (1998) Molecular cloning and expression of rat contraception associated protein 1 (CAP1), a protein putatively involved in fertilization. Biochem. Biophys. Res. Commun. 251, 545–549.
Wakabayashi K., Hansen L., Vincent I., Mallory M., and Masliah E. (1997) Neurofibrillary tangles in the dentate granule cells in Alzheimer’s disease, Lewy body disease and progressive supranuclear palsy. Acta. Neuropathol. 93, 7–12.
Walsh D., Tseng B., Rydel R., Podlisny M., and Selkoe D. (2000) The oligomerization of amyloid beta-protein begins intracellularly in cells derived from human brain. Biochemistry 39, 10831–10839.
Weinreb P., Zhen W., Poon A., Conway K., and Lansbury P. J. (1996) NACP, a protein implicated in Alzheimer’s disease and learning, is natively unfolded. Biochemistry 35, 13709–13715.
Wood S. J., Wypych J., Steavenson S., et al. (1999) α-Synuclein fibrillogenesis is nucleation dependent. Implications for the pathogenesis of Parkinson’s disease. J. Biol. Chem. 274, 19509–19512.
Yamin G., Glaser C. B., Uversky V. N., and Fink A. L. (2003) Certain metals trigger fibrillation of methionine-oxidized alpha-synuclein. J. Biol. Chem. 278, 27630–27635. Epub 2003 May 16.
Yang F., Ueda K., Chen P., Ashe K. H., and Cole G. M. (2000) Plaque-associated alpha-synuclein (NACP) pathology in aged transgenic mice expressing amyloid precursor protein. Brain Res. 853, 381–383.
Youdim M. B., Ben-Shachar D., Riederer P. (1994) The enigma of neuromelanin in Parkinson’s disease substantia nigra. J. Neural. Transm. Suppl. 43, 113–122.
Younkin S. G. (1997) The AAP and PS1/2 mutations linked to early onset familial Alzheimer’s disease increase the extracellular concentration and A beta 1–42 (43). Rinsho. Shinkeigaku. 37, 1099.
About this article
Cite this article
Hashimoto, M., Rockenstein, E., Crews, L. et al. Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer’s and Parkinson’s diseases. Neuromol Med 4, 21–35 (2003). https://doi.org/10.1385/NMM:4:1-2:21
- Alzheimer’s disease
- dementia with Lewy bodies
- synapse damage
- mitochondrial dysfunction
- protein misfolding
- plasma membrane