Alpha-synuclein in Parkinson's disease: a villain or tragic hero? A critical view of the formation of α-synuclein aggregates induced by dopamine metabolites and viral infection

References

• Langston JW. The Parkinson’s complex: parkinsonism is just the tip of the iceberg. Ann Neurol. 2006;59:591–596.
   PubMed Web of Science ®Google Scholar
• Pringsheim T, Jette N, Frolkis A, et al. The prevalence of Parkinson’s disease: a systematic review and meta-analysis. Mov Disord. 2014;29:1583–1590.
   PubMed Web of Science ®Google Scholar
• Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008;79:368–376.
   PubMed Web of Science ®Google Scholar
• Paracha M, Herbst K, Kieburtz K, et al. Prevalence and incidence of nonmotor symptoms in individuals with and without Parkinson’s disease. Mov Disord Clin Pract. 2022;9:961–966.
   PubMedGoogle Scholar
• Deng H, Wang P, Jankovic J. The genetics of Parkinson´s disease. Ageing Res Rev. 2018;42:72–85.
   PubMed Web of Science ®Google Scholar
• Dauer W, Przedborski S. Parkinson’s disease: mechanisms and models. Neuron. 2003;39:889–909.
   PubMed Web of Science ®Google Scholar
• Kordower JH, Olanow CW, Dodiya HB, et al. Disease duration and the integrity of the nigrostriatal system in Parkinson’s disease. Brain. 2013;136:2419–2431.
   PubMed Web of Science ®Google Scholar
• Spillantini MG, Schmidt ML, Lee VMY, et al. Alpha-synuclein in Lewy bodies. Nature. 1997;388:839–840.
   PubMed Web of Science ®Google Scholar
• Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science. 1997;276:2045–2047.
   PubMed Web of Science ®Google Scholar
• Kruger R, Kuhn W, Muller T, et al. Ala30pro mutation in the gene encoding alpha-synuclein in Parkinson’s disease. Nat Genet. 1998;18:106–108.
   PubMed Web of Science ®Google Scholar
• Zarranz JJ, Alegre J, Gomez-Esteban JC, et al. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol. 2004;55:164–173.
   PubMed Web of Science ®Google Scholar
• Appel-Cresswell S, Vilarino-Guell C, Encarnacion M, et al. Alpha-synuclein p.H50q, a novel pathogenic mutation for Parkinson’s disease. Mov Disord. 2013;28:811–813.
   PubMed Web of Science ®Google Scholar
• Lesage S, Anheim M, Letournel F, et al. G51D alpha-synuclein mutation causes a novel parkinsonian-pyramidal syndrome. Ann Neurol. 2013;73:459–471.
   PubMed Web of Science ®Google Scholar
• Pasanen P, Myllykangas L, Siitonen M, et al. Novel α-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson’s disease-type pathology. Neurobiol Aging. 2014;35:2180.e1–5.
   PubMedGoogle Scholar
• Kahle PJ. Alpha-synucleinopathy models and human neuropathology: similarities and differences. Acta Neuropathol. 2008;115:87–95.
   PubMed Web of Science ®Google Scholar
• Specht CG, Tigaret CM, Rast GF, et al. Subcellular localisation of recombinant alpha- and gamma-synuclein. Mol Cell Neurosci. 2005;28:326–334.
   PubMedGoogle Scholar
• Vamvaca K, Volles MJ, Lansbury JP. The first N-terminal amino acids of α-synuclein are essential for α-helical structure formation in vitro and membrane binding in yeast. J Mol Biol. 2009;389:413–424.
   PubMedGoogle Scholar
• Davidson WS, Jonas A, Clayton DF, et al. Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J Biol Chem. 1998;273:9443–9449.
   PubMed Web of Science ®Google Scholar
• Georgieva ER, Ramlall TF, Borbat PP, et al. Membrane-bound α-synuclein forms an extended helix: long-distance pulsed ESR measurements using vesicles, bicelles, and rodlike micelles. J Am Chem Soc. 2008;130:12856–12857.
   PubMedGoogle Scholar
• Tofaris GK, Spillantini MG. Alpha-synuclein dysfunction in Lewy body diseases. Mov Disord. 2005;20:37–S44.
   PubMedGoogle Scholar
• Fortin DL, Nemani VM, Nakamura K, et al. The behavior of alpha-synuclein in neurons. Mov Disord. 2010;25:21–S26.
   Google Scholar
• Burré J, Sharma M, Tsetsenis T, et al. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science. 2010;329:1663–1667.
   PubMed Web of Science ®Google Scholar
• Calì T, Ottolini D, Negro A, et al. α-synuclein controls mitochondrial calcium homeostasis by enhancing endoplasmic reticulum-mitochondria interactions. J Biol Chem. 2012;287:17914–17929.
   PubMed Web of Science ®Google Scholar
• Zhu M, Qin ZJ, Hu D, et al. Alpha-synuclein can function as an antioxidant preventing oxidation of unsaturated lipid in vesicles. Biochemistry. 2006;45:8135–8142.
   PubMedGoogle Scholar
• Volles MJ, Lansbury PT Jr. Vesicle permeabilization by protofibrillar alpha-synuclein is sensitive to Parkinson’s disease-linked mutations and occurs by a pore-like mechanism. Biochemistry. 2002;41:4595–4602.
   PubMed Web of Science ®Google Scholar
• Reynolds NP, Soragni A, Rabe M, et al. Mechanism of membrane interaction and disruption by α-synuclein. J Am Chem Soc. 2011;133:19366–19375.
   PubMedGoogle Scholar
• Tosatto L, Andrighetti AO, Plotegher N, et al. Alpha-synuclein pore forming activity upon membrane association. Biochim Biophys Acta. 2012;1818:2876–2883.
   PubMedGoogle Scholar
• Boi L, Pisanu A, Palmas MF, et al. Modeling Parkinson’s disease neuropathology and symptoms by intranigral inoculation of preformed human α-synuclein oligomers. Int J Mol Sci. 2020;21:8535.
   PubMedGoogle Scholar
• Nakamura K, Nemani VM, Azarbal F, et al. Direct membrane association drives mitochondrial fission by the Parkinson disease-associated protein alpha-synuclein. J Biol Chem. 2011;286:20710–20726.
   PubMed Web of Science ®Google Scholar
• Choi BK, Choi MG, Kim JY, et al. Large α-synuclein oligomers inhibit neuronal SNARE-mediated vesicle docking. Proc Natl Acad Sci, USA. 2013;110:4087–4092.
   PubMed Web of Science ®Google Scholar
• Garcia-Esparcia P, Hernández-Ortega K, Koneti A, et al. Altered machinery of protein synthesis is region- and stage-dependent and is associated with α-synuclein oligomers in Parkinson’s disease. Acta Neuropathol Commun. 2015;3:76.
   PubMedGoogle Scholar
• Danzer KM, Haasen D, Karow AR, et al. Different species of alpha-synuclein oligomers induce calcium influx and seeding. J Neurosci. 2007;27:9220–9232.
   PubMed Web of Science ®Google Scholar
• Cascella R, Chen SW, Bigi A, et al. The release of toxic oligomers from α-synuclein fibrils induces dysfunction in neuronal cells. Nat Commun. 2021;12:1814.
   PubMedGoogle Scholar
• Guo M, Wang J, Zhao Y, et al. Microglial exosomes facilitate α-synuclein transmission in Parkinson’s disease. Brain. 2020;143:1476–1497.
   PubMed Web of Science ®Google Scholar
• Kayed R, Dettmer U, Lesné SE. Soluble endogenous oligomeric α-synuclein species in neurodegenerative diseases: expression, spreading, and cross-talk. J Parkinson's Dis. 2020;10:791–818.
   PubMedGoogle Scholar
• Fan HF, Chen WL, Chen YZ, et al. Change in the oligomeric state of α-synuclein variants in living cells. ACS Chem Neurosci. 2022;13:1143–1164.
   PubMedGoogle Scholar
• Lázaro DF, Rodrigues EF, Langohr R, et al. Systematic comparison of the effects of alpha-synuclein mutations on its oligomerization and aggregation. PLoS Genet. 2014;10:e1004741.
   PubMedGoogle Scholar
• Masato A, Plotegher N, Boassa D, et al. Impaired dopamine metabolism in Parkinson’s disease pathogenesis. Mol Neurodegener. 2019;14:35.
   PubMed Web of Science ®Google Scholar
• Goldstein DS, Sullivan P, Holmes C, et al. Catechols in post-mortem brain of patients with Parkinson disease. Eur J Neurol. 2011;18:703–710.
   PubMed Web of Science ®Google Scholar
• Bisaglia M, Mammi S, Bubacco L. Kinetic and structural analysis of the early oxidation products of dopamine: analysis of the interactions with alpha-synuclein. J Biol Chem. 2007;282:15597–15605.
   PubMedGoogle Scholar
• Lisenbardt AJ, Breckenridge JM, Wilken GH, et al. Dopaminochrome induces caspase-independent apoptosis in the mesencephalic cell line, MN9D. J Neurochem. 2012;122:175–184.
   PubMedGoogle Scholar
• Segura-Aguilar J, Metodiewa D, Welch CJ. Metabolic activation of dopamine o-quinones to o-semiquinones by NADPH cytochrome P450 reductase may play an important role in oxidative stress and apoptotic effects. Biochim Biophys Acta. 1998;1381:1–6.
   PubMed Web of Science ®Google Scholar
• Mor DE, Daniels MJ, Ischiropoulos H. The usual suspects, dopamine and alpha-synuclein, conspire to cause neurodegeneration. Mov Disord. 2019;34:167–179.
   PubMed Web of Science ®Google Scholar
• Conway KA, Rochet JC, Bieganski RM, et al. Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Science. 2001;294:1346–1349.
   PubMed Web of Science ®Google Scholar
• Norris EH, Giasson BI, Hodara R, et al. Reversible inhibition of α-synuclein fibrillization by dopaminochrome-mediated conformational alterations. J Biol Chem. 2005;280:21212–21219.
   PubMed Web of Science ®Google Scholar
• Li HT, Lin DH, Luo XY, et al. Inhibition of alpha-synuclein fibrillization by dopamine analogs via reaction with the amino groups of alpha-synuclein. Implication for dopaminergic neurodegeneration. FEBS J. 2005;272:3661–3672.
   PubMed Web of Science ®Google Scholar
• Follmer C, Romão L, Einsiedler CM, et al. Dopamine affects the stability, hydration, and packing of protofibrils and fibrils of the wild type and variants of alpha-synuclein. Biochemistry. 2007;46:472–482.
   PubMedGoogle Scholar
• Wey MC, Fernandez E, Martinez PA, et al. Neurodegeneration and motor dysfunction in mice lacking cytosolic and mitochondrial aldehyde dehydrogenases: implications for Parkinson’s disease. PLoS ONE. 2012;7:e31522.
   PubMed Web of Science ®Google Scholar
• Meiser J, Weindl D, Hiller K. Complexity of dopamine metabolism. Cell Commun Signal. 2013;11:34.
   PubMed Web of Science ®Google Scholar
• Goldstein DS, Kopin IJ, Sharabi Y. Catecholamine autotoxicity. Implications for pharmacology and therapeutics of Parkinson´s disease and related disorders. Pharmacol Ther. 2014;144:268–282.
   PubMedGoogle Scholar
• Sparks DL, Woeltz VM, Markesbery WR. Alterations in brain monoamine oxidase activity in aging, Alzheimer’s disease, and Pick’s disease. Arch Neurol. 1991;48:718–721.
   PubMedGoogle Scholar
• Goldstein DS, Sullivan P, Holmes C, et al. Determinants of buildup of the toxic dopamine metabolite DOPAL in Parkinson’s disease. J Neurochem. 2013;126:591–603.
   PubMed Web of Science ®Google Scholar
• Kristal BS, Conway AD, Brown AM, et al. Selective dopaminergic vulnerability: 3,4-dihydroxyphenylacetaldehyde targets mitochondria. Free Radic Biol Med. 2001;30:924–931.
   PubMedGoogle Scholar
• Goldstein DS, Sullivan P, Cooney A, et al. Vesicular uptake blockade generates the toxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde in PC12 cells: relevance to the pathogenesis of Parkinson’s disease. J Neurochem. 2012;123:932–943.
   PubMed Web of Science ®Google Scholar
• Legros H, Dingeval MG, Janin F, et al. Toxicity of a treatment associating dopamine and disulfiram for catecholaminergic neuroblastoma SH-SY5Y cells: relationships with 3,4-dihydroxyphenylacetaldehyde formation. Neurotoxicology. 2004;25:365–375.
   PubMed Web of Science ®Google Scholar
• Burke WJ, Kumar VB, Pandey N, et al. Aggregation of alpha-synuclein by DOPAL, the monoamine oxidase metabolite of dopamine. Acta Neuropathol. 2008;115:193–203.
   PubMed Web of Science ®Google Scholar
• Florang VR, Rees JN, Brogden NK, et al. Inhibition of the oxidative metabolism of 3,4-dihydroxyphenylacetaldehyde, a reactive intermediate of dopamine metabolism, by 4-hydroxy-2-nonenal. Neurotoxicology. 2007;28:76–82.
   PubMed Web of Science ®Google Scholar
• Selley ML. (E)-4-hydroxy-2-nonenal may be involved in the pathogenesis of Parkinson’s disease. Free Radic Biol Med. 1998;25:169–174.
   PubMed Web of Science ®Google Scholar
• Castellani RJ, Perry G, Siedlak SL, et al. Hydroxynonenal adducts indicate a role for lipid peroxidation in neocortical and brainstem Lewy bodies in humans. Neurosci Lett. 2002;319:25–28.
   PubMed Web of Science ®Google Scholar
• Goldstein DS, Sullivan P, Holmes C, et al. Decreased vesicular storage and aldehyde dehydrogenase activity in multiple system atrophy. Parkinsonism Relat Disord. 2015;21:567–572.
   PubMed Web of Science ®Google Scholar
• Werner-Allen JW, Levine RL, Bax A. Superoxide is the critical driver of DOPAL autoxidation, lysyl adduct formation, and crosslinking of α-synuclein. Biochem Biophys Res Commun. 2017;487:281–286.
   PubMedGoogle Scholar
• Li SW, Lin T-S, Minteer WJ. 3,4-dihydroxyphenylacetaldehyde and hydrogen peroxide generate a hydroxyl radical: possible role in Parkinson’s disease pathogenesis. Mol Brain Res. 2001;93:1–7.
   PubMedGoogle Scholar
• Follmer C, Coelho-Cerqueira E, Yatabe-Franco DY, et al. Oligomerization and membrane binding properties of covalent adducts formed by the interaction of α-synuclein with the toxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). J Biol Chem. 2015;290:27660–27679.
   PubMedGoogle Scholar
• Rees JN, Florang VR, Eckert LL, et al. Protein Reactivity of 3,4- dihydroxyphenylacetaldehyde, a toxic dopamine metabolite, is dependent on both the aldehyde and catechol. Chem Res Toxicol. 2009;22:1256–1263.
   PubMed Web of Science ®Google Scholar
• Plotegher N, Berti G, Ferrari E, et al. DOPAL derived alpha-synuclein oligomers impair synaptic vesicles physiological function. Sci Rep. 2017;7:40699.
   PubMed Web of Science ®Google Scholar
• Alves da Costa CA, Ancolio K, Checler F. Wild-type but not Parkinson’s disease-related ala-53-Thr mutant alpha-synuclein protects neuronal cells from apoptotic stimuli. J Biol Chem. 2000;275:24065–24069.
   PubMedGoogle Scholar
• Akintade DD, Chaudhuri B. The effect of copy number on α-synuclein’s toxicity and its protective role in Bax-induced apoptosis, in yeast. Biosci Rep. 2020;40:BSR20201912.
   PubMedGoogle Scholar
• Menges S, Minakaki G, Schaefer PM, et al. Alpha-synuclein prevents the formation of spherical mitochondria and apoptosis under oxidative stress. Sci Rep. 2017;7:42942.
   PubMed Web of Science ®Google Scholar
• Alves Da Costa C, Paitel E, Vincent B, et al. Alpha-synuclein lowers p53-dependent apoptotic response of neuronal cells. Abolishment by 6-hydroxydopamine and implication for Parkinson’s disease. J Biol Chem. 2002;277:50980–50984.
   PubMed Web of Science ®Google Scholar
• Jensen PJ, Alter BJ, O’malley KL. Alpha-synuclein protects naive but not dbcAMP-treated dopaminergic cell types from 1-methyl-4-phenylpyridinium toxicity. J Neurochem. 2003;86:196–209.
   PubMedGoogle Scholar
• Machida Y, Chiba T, Takayanagi A, et al. Common anti-apoptotic roles of parkin and alpha-synuclein in human dopaminergic cells. Biochem Biophys Res Commun. 2005;332:233–240.
   PubMed Web of Science ®Google Scholar
• Manning-Bog AB, McCormack AL, Purisai MG, et al. Alpha-synuclein overexpression protects against paraquat-induced neurodegeneration. J Neurosci. 2003;23:3095–3099.
   PubMed Web of Science ®Google Scholar
• Carmo-Gonçalves P, Romão L, Follmer C. In vitro protective action of monomeric and fibrillar α-synuclein on neuronal cells exposed to the dopaminergic toxins salsolinol and DOPAL. ACS Chem Neurosci. 2020;11:3541–3548.
   PubMedGoogle Scholar
• Deng Y, Maruyama W, Dostert P, et al. Determination of the (R)- and (S)-enantiomers of salsolinol and N-methyl-salsolinol by use of a chiral high performance liquid chromatographic column. J Chromatogr B. 1995;670:47–54.
   PubMedGoogle Scholar
• DeCuypere M, Lu Y, Miller DD, et al. Regional distribution of tetrahydroisoquinoline derivatives in rodent, human, and Parkinson’s disease brain. J Neurochem. 2008;107:1398–1413.
   PubMedGoogle Scholar
• Kurnik M, Gil K, Gaida M, et al. Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol. Folia Histochem Cytobiol. 2015;53:49–61.
   PubMedGoogle Scholar
• Smeyne RJ, Noyce AJ, Byrne M, et al. Infection and risk of Parkinson’s disease. J Parkinsons Dis. 2021;11:31–43.
   PubMedGoogle Scholar
• Grathwohl S, Quansah E, Maroof N, et al. Specific immune modulation of experimental colitis drives enteric alpha-synuclein accumulation and triggers age-related Parkinson-like brain pathology. Free Neuropathol. 2021;2:13.
   Google Scholar
• Labrie V, Brundin P. Alpha-synuclein to the rescue: immune cell recruitment by alpha-synuclein during gastrointestinal infection. J Innate Immun. 2017;9:437–440.
   PubMedGoogle Scholar
• Stolzenberg E, Berry D, Yang D, et al. A role for neuronal alpha-synuclein in gastrointestinal immunity. J Innate Immun. 2017;9:456–463.
   PubMedGoogle Scholar
• Monogue B, Chen Y, Sparks H, et al. Alpha-synuclein supports type 1 interferon signalling in neurons and brain tissue. Brain. 2022;145:3622–3636.
   PubMedGoogle Scholar
• Winner B, Regensburger M, Schreglmann S, et al. Role of α-synuclein in adult neurogenesis and neuronal maturation in the dentate gyrus. J Neurosci. 2012;32:16906–16916.
   PubMedGoogle Scholar
• Beatman EL, Massey A, Shives KD, et al. Alpha-synuclein expression restricts RNA viral infections in the brain. J Virol. 2016;90:2767–2782.
   Google Scholar
• Jang H, Boltz D, Sturm-Ramirez K, et al. Highly pathogenic H5N1 influenza virus can enter the central nervous system and induce neuroinflammation and neurodegeneration. Proc Natl Acad Sci, USA. 2009;106:14063–14068.
   PubMed Web of Science ®Google Scholar
• Santerre M, Arjona SP, Allen CN, et al. HIV-1 Vpr protein impairs lysosome clearance causing SNCA/alpha-synuclein accumulation in neurons. Autophagy. 2021;17:1768–1782.
   PubMedGoogle Scholar
• Antonini A, Leta V, Teo J, et al. Outcome of Parkinson’s disease patients affected by COVID-19. Mov Disord. 2020;35:905–908.
   PubMed Web of Science ®Google Scholar
• Follmer C. Gut microbiome imbalance and neuroinflaMMATIOn: impact of COVID-19 on Parkinson’s disease. Mov Disord. 2020;35(9):1495–1496.
   PubMedGoogle Scholar
• Follmer C. Viral infection-induced gut dysbiosis, neuroinflammation, and α-synuclein aggregation: updates and perspectives on COVID-19 and neurodegenerative disorders. ACS Chem Neurosci. 2020;11:4012–4016.
   PubMedGoogle Scholar
• Semerdzhiev SA, Fakhree MAA, Segers-Nolten I, et al. Interactions between SARS-CoV-2 N-protein and α-synuclein accelerate amyloid formation. ACS Chem Neurosci. 2022;13:143–150.
   PubMed Web of Science ®Google Scholar
• Philippens IHCHM, Böszörményi KP, Wubben JAM, et al. Brain inflammation and intracellular α-synuclein aggregates in macaques after SARS-CoV-2 infection. Viruses. 2022;14:776.
   PubMedGoogle Scholar
• Chapman G, Beaman BL, Loeffler DA, et al. In situ hybridization for detection of nocardial 16S rRNA: reactivity within intracellular inclusions in experimentally infected cynomolgus monkeys–and in Lewy body-containing human brain specimens. Exp Neurol. 2003;184:715–725.
   PubMedGoogle Scholar
• Choi JG, Kim N, Ju IG, et al. Oral administration of Proteus mirabilis damages dopaminergic neurons and motor functions in mice. Sci Rep. 2018;8:1275.
   PubMedGoogle Scholar
• Bukhbinder AS, Ling Y, Hasan O, et al. Risk of Alzheimer’s disease following influenza vaccination: a claims-based cohort study using propensity score matching. J Alzheimers Dis. 2022;88:1061–1074.
   PubMedGoogle Scholar
• Yang Y, He Z, Xing Z, et al. Influenza vaccination in early Alzheimer’s disease rescues amyloidosis and ameliorates cognitive deficits in APP/PS1 mice by inhibiting regulatory T cells. J Neuroinflam. 2020;17:65.
   PubMed Web of Science ®Google Scholar
• Liu JC, Hsu YP, Kao PF, et al. Influenza vaccination reduces dementia risk in chronic kidney disease patients: a population-based cohort study. Medicine. 2016;95:e2868.
   PubMedGoogle Scholar
• Schnier C, Janbek J, Lathe R, et al. Reduced dementia incidence after varicella zoster vaccination in Wales 2013-2020. Alzheimers Dement. 2022;8:e12293.
   Google Scholar
• Wozniak MA, Itzhaki RF, Shipley SJ, et al. Herpes simplex virus infection causes cellular beta-amyloid accumulation and secretase upregulation. Neurosci Lett. 2007;429:95–100.
   PubMed Web of Science ®Google Scholar
• Agostini S, Mancuso R, Costa AS, et al. A possible role for HSV-1-specific humoral response and PILRA rs1859788 polymorphism in the pathogenesis of Parkinson’s disease. Vaccines. 2021;9:686.
   Google Scholar
• Follmer C. Monoamine oxidase and α-synuclein as targets in Parkinson’s disease therapy. Expert Rev Neurother. 2014;14:703–716.
   PubMed Web of Science ®Google Scholar
• Lindström V, Fagerqvist T, Nordström E, et al. Immunotherapy targeting α-synuclein protofibrils reduced pathology in (Thy-1)-h[a30p] α-synuclein mice. Neurobiol Dis. 2014;69:134–143.
   PubMed Web of Science ®Google Scholar
• Yeo-Teh NSL, Tang BL. A review of scientific ethics issues associated with the recently approved drugs for Alzheimer’s disease. Sci Eng Ethics. 2023;29:2.
   PubMedGoogle Scholar
• Haass C, Selkoe D. If amyloid drives Alzheimer disease, why have anti-amyloid therapies not yet slowed cognitive decline? PLoS Biol. 2022;20:e3001694.
   PubMedGoogle Scholar
• van Dyck Ch, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388:9–21.
   PubMed Web of Science ®Google Scholar
• Lang AE, Siderowf AD, Macklin EA, et al. Trial of cinpanemab in early Parkinson’s disease. N Engl J Med. 2022;387:408–420.
   PubMed Web of Science ®Google Scholar
• Pagano G, Taylor KI, Anzures-Cabrera J, et al. Trial of prasinezumab in early-stage Parkinson’s disease. N Engl J Med. 2022;387:421–432.
   PubMed Web of Science ®Google Scholar