Calabresi P, Mechelli A, Natale G, Volpicelli-Daley L, Di Lazzaro G, Ghiglieri V. Alpha-synuclein in Parkinson’s disease and other synucleinopathies: from overt neurodegeneration back to early synaptic dysfunction. Cell Death Dis. 2023;14(3):176.

Article  PubMed  PubMed Central  Google Scholar 

Burré J, Sharma M, Südhof TC. Cell biology and pathophysiology of α-synuclein. Cold Spring Harb Perspect Med. 2018;8(3):a0240918.

Iba M, Kim C, Florio J, Mante M, Adame A, Rockenstein E, Kwon S, Rissman R, Masliah E. Role of Alterations in Protein Kinase p38γ in the Pathogenesis of the Synaptic Pathology in Dementia With Lewy Bodies and α-Synuclein Transgenic Models. Front Neurosci. 2020;14:286.

Article  PubMed  PubMed Central  Google Scholar 

Tozzi A, de Iure A, Bagetta V, Tantucci M, Durante V, Quiroga-Varela A, Costa C, Di Filippo M, Ghiglieri V, Latagliata EC, et al. Alpha-Synuclein Produces Early Behavioral Alterations via Striatal Cholinergic Synaptic Dysfunction by Interacting With GluN2D N-Methyl-D-Aspartate Receptor Subunit. Biol Psychiat. 2016;79(5):402–14.

Article  CAS  PubMed  Google Scholar 

Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, Cummings J, van der Flier WM. Alzheimer’s disease. Lancet (London, England). 2021;397(10284):1577–90.

Article  CAS  PubMed  Google Scholar 

Barnes LL, Leurgans S, Aggarwal NT, Shah RC, Arvanitakis Z, James BD, Buchman AS, Bennett DA, Schneider JA. Mixed pathology is more likely in black than white decedents with Alzheimer dementia. Neurology. 2015;85(6):528–34.

Article  PubMed  PubMed Central  Google Scholar 

Korff A, Liu C, Ginghina C, Shi M, Zhang J. Alzheimer’s Disease Neuroimaging I: alpha-Synuclein in cerebrospinal fluid of Alzheimer’s disease and mild cognitive impairment. J Alzheimers Dis. 2013;36(4):679–88.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kapaki E, Paraskevas GP, Emmanouilidou E, Vekrellis K. he diagnostic value of CSF α-synuclein in the differential diagnosis of dementia with Lewy bodies vs. normal subjects and patients with Alzheimer’s disease. PloS one. 2013;8(11):e81654.

Article  PubMed  PubMed Central  Google Scholar 

Ohrfelt A, Grognet P, Andreasen N, Wallin A, Vanmechelen E, Blennow K, Zetterberg H. Cerebrospinal fluid alpha-synuclein in neurodegenerative disorders-a marker of synapse loss? Neurosci Lett. 2009;450(3):332–5.

Article  PubMed  Google Scholar 

Jellinger KA. Interaction between pathogenic proteins in neurodegenerative disorders. J Cell Mol Med. 2012;16(6):1166–83.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Clinton LK, Blurton-Jones M, Myczek K, Trojanowski JQ, LaFerla FM. Synergistic Interactions between Abeta, tau, and alpha-synuclein: acceleration of neuropathology and cognitive decline. J Neurosci. 2010;30(21):7281–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ferman TJ, Aoki N, Boeve BF, Aakre JA, Kantarci K, Graff-Radford J, Parisi JE, Van Gerpen JA, Graff-Radford NR, Uitti RJ, et al. Subtypes of dementia with Lewy bodies are associated with α-synuclein and tau distribution. Neurology. 2020;95(2):e155–65.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shim KH, Kang MJ, Youn YC, An SSA, Kim S. Alpha-synuclein: a pathological factor with Aβ and tau and biomarker in Alzheimer’s disease. Alzheimer’s research & therapy. 2022;14(1):201.

Article  CAS  Google Scholar 

Ferman TJ, Aoki N, Crook JE, Murray ME, Graff-Radford NR, van Gerpen JA, Uitti RJ, Wszolek ZK, Graff-Radford J, Pedraza O, et al. The limbic and neocortical contribution of α-synuclein, tau, and amyloid β to disease duration in dementia with Lewy bodies. Alzheimers Dement. 2018;14(3):330–9.

Article  PubMed  Google Scholar 

Bearoff F, Dhavale D, Kotzbauer P, Kortagere S. Aggregated alpha-synuclein transcriptionally activates pro-inflammatory canonical and non-canonical NF-kappaB signaling pathways in peripheral monocytic cells. Mol Immunol. 2023;154:1–10.

Article  CAS  PubMed  Google Scholar 

Klegeris A, Giasson BI, Zhang H, Maguire J, Pelech S, McGeer PL. Alpha-synuclein and its disease-causing mutants induce ICAM-1 and IL-6 in human astrocytes and astrocytoma cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2006;20(12):2000–8.

Article  CAS  PubMed  Google Scholar 

Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R, Hansen LA, Katzman R. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991;30(4):572–80.

Article  CAS  PubMed  Google Scholar 

Outeiro TF, Koss DJ, Erskine D, Walker L, Kurzawa-Akanbi M, Burn D, Donaghy P, Morris C, Taylor JP, Thomas A, et al. Dementia with Lewy bodies: an update and outlook. Mol Neurodegener. 2019;14(1):5.

Article  PubMed  PubMed Central  Google Scholar 

Beach TG, Adler CH, Lue L, Sue LI, Bachalakuri J, Henry-Watson J, Sasse J, Boyer S, Shirohi S, Brooks R, et al. Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction. Acta Neuropathol. 2009;117(6):613–34.

Article  PubMed  PubMed Central  Google Scholar 

Kasuga K, Tokutake T, Ishikawa A, Uchiyama T, Tokuda T, Onodera O, Nishizawa M, Ikeuchi T. Differential levels of alpha-synuclein, beta-amyloid42 and tau in CSF between patients with dementia with Lewy bodies and Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2010;81(6):608–10.

Article  PubMed  Google Scholar 

Van Hulle C, Jonaitis EM, Betthauser TJ, Batrla R, Wild N, Kollmorgen G, Andreasson U, Okonkwo O, Bendlin BB, Asthana S, et al. An examination of a novel multipanel of CSF biomarkers in the Alzheimer’s disease clinical and pathological continuum. Alzheimers Dement. 2021;17(3):431–45.

Article  PubMed  Google Scholar 

Slaets S, Vanmechelen E, Le Bastard N, Decraemer H, Vandijck M, Martin JJ, De Deyn PP, Engelborghs S. Increased CSF alpha-synuclein levels in Alzheimer’s disease: correlation with tau levels. Alzheimers Dement. 2014;10(5 Suppl):S290–298.

PubMed  Google Scholar 

Twohig D, Rodriguez-Vieitez E, Sando SB, Berge G, Lauridsen C, Moller I, Grontvedt GR, Brathen G, Patra K, Bu G, et al. The relevance of cerebrospinal fluid alpha-synuclein levels to sporadic and familial Alzheimer’s disease. Acta Neuropathol Commun. 2018;6(1):130.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Toledo JB, Korff A, Shaw LM, Trojanowski JQ, Zhang J. CSF α-synuclein improves diagnostic and prognostic performance of CSF tau and Aβ in Alzheimer’s disease. Acta Neuropathol. 2013;126(5):683–97.

Article  CAS  PubMed  Google Scholar 

Parnetti L, Chiasserini D, Bellomo G, Giannandrea D, De Carlo C, Qureshi MM, Ardah MT, Varghese S, Bonanni L, Borroni B, et al. Cerebrospinal fluid Tau/α-synuclein ratio in Parkinson’s disease and degenerative dementias. Movement disorders : official journal of the Movement Disorder Society. 2011;26(8):1428–35.

Article  PubMed  Google Scholar 

Cousins KAQ, Arezoumandan S, Shellikeri S, Ohm D, Shaw LM, Grossman M, Wolk D, McMillan CT, Chen-Plotkin A, Lee E, et al. CSF Biomarkers of Alzheimer Disease in Patients With Concomitant α-Synuclein Pathology. Neurology. 2022;99(20):e2303–12.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dasari AKR, Kayed R, Wi S, Lim KH. Tau Interacts with the C-Terminal Region of α-Synuclein, Promoting Formation of Toxic Aggregates with Distinct Molecular Conformations. Biochemistry. 2019;58(25):2814–21.

Article  CAS  PubMed  Google Scholar 

Qureshi HY, Paudel HK. Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and alpha-synuclein mutations promote Tau protein phosphorylation at Ser262 and destabilize microtubule cytoskeleton in vitro. J Biol Chem. 2011;286(7):5055–68.

Article  CAS  PubMed  Google Scholar 

Guo JL, Covell DJ, Daniels JP, Iba M, Stieber A, Zhang B, Riddle DM, Kwong LK, Xu Y, Trojanowski JQ, et al. Distinct α-synuclein strains differentially promote tau inclusions in neurons. Cell. 2013;154(1):103–17.

Article  CAS  PubMed  Google Scholar 

Oikawa T, Nonaka T, Terada M, Tamaoka A, Hisanaga S, Hasegawa M. α-Synuclein Fibrils Exhibit Gain of Toxic Function, Promoting Tau Aggregation and Inhibiting Microtubule Assembly. J Biol Chem. 2016;291(29):15046–56.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Smirnov DS, Salmon DP, Galasko D, Goodwill VS, Hansen LA, Zhao Y, Edland SD, Léger GC, Peavy GM, Jacobs DM, et al. Association of Neurofibrillary Tangle Distribution With Age at Onset-Related Clinical Heterogeneity in Alzheimer Disease: An Autopsy Study. Neurology. 2022;98(5):e506–17.

Article  CAS  PubMed  PubMed Central  Google Scholar 

McCoy MK, Tansey MG. TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease. J Neuroinflammation. 2008;5:45.

Article  PubMed  PubMed Central  Google Scholar 

Williams SK, Maier O, Fischer R, Fairless R, Hochmeister S, Stojic A, Pick L, Haar D, Musiol S, Storch MK, et al. Antibody-mediated inhibition of TNFR1 attenuates disease in a mouse model of multiple sclerosis. PLoS ONE. 2014;9(2): e90117.

Article  PubMed  PubMed Central  Google Scholar 

Montgomery SL, Narrow WC, Mastrangelo MA, Olschowka JA, O’Banion MK, Bowers WJ. Chronic neuron- and age-selective down-regulation of TNF receptor expression in triple-transgenic Alzheimer disease mice leads to significant modulation of amyloid- and Tau-related pathologies. Am J Pathol. 2013;182(6):2285–97.

Article  CAS  PubMed