Cited by 879Alzheimer's disease research and treatmentsParkinson's Disease Mechanisms and TreatmentsPrion Diseases and Protein Misfolding

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Initiation and Synergistic Fibrillization of Tau and Alpha-Synuclein

Giasson, Benoit I., Forman, Mark S., Higuchi, Makoto, Golbe, Lawrence I., Graves, Charles L., Kotzbauer, Paul T., Trojanowski, John Q., Lee, Virginia M.-Y.·2003·Science

DOI 10.1126/science.1082324

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Abstract

Alpha-synuclein (alpha-syn) and tau polymerize into amyloid fibrils and form intraneuronal filamentous inclusions characteristic of neurodegenerative diseases. We demonstrate that alpha-syn induces fibrillization of tau and that coincubation of tau and alpha-syn synergistically promotes fibrillization of both proteins. The in vivo relevance of these findings is grounded in the co-occurrence of alpha-syn and tau filamentous amyloid inclusions in humans, in single transgenic mice that express A53T human alpha-syn in neurons, and in oligodendrocytes of bigenic mice that express wild-type human alpha-syn plus P301L mutant tau. This suggests that interactions between alpha-syn and tau can promote their fibrillization and drive the formation of pathological inclusions in human neurodegenerative diseases.

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Background
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Background
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“Accruing evidence suggest neurodegenerative events often involve co-occurring proteinopathies [8,9].”
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Amygdala-predominant α-synuclein pathology exacerbates hippocampal neuron loss in Alzheimer’s diseasePreprint
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“In vitro , cross-seeding has been demonstrated for α -synuclein fibrils seeding tau monomers (8), A β fibrils seeding islet amyloid polypeptide (IAPP) (9), seeding between wild-type and mutant A β (10), and truncated α -synuclein fibrils seeding full-length α -synuclein monomers (11).”
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“…previous characteri-sations of the A53T model, which indicate that neurode-generation in the CNS of A53T mice typically manifests at 32–48 weeks (Giasson et al. 2003, Han et al. 2025, Mondal et al., 2021, Oaks et al. 2013, Paumier et al. 2013) while gut manifestations present between 12 and 20…”
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“In vitro aggregation assays have shown that co-incubation of tau and α-synuclein promotes the aggregation of both protein species (Giasson et al., 2003).”
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EKSOZOMLAR VE NÖRODEJENERATİF HASTALIKLARLA İLİŞKİSİ
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Lewy Bodies in Conditions other than Disorders of α‐Synuclein
Paisán‐Ruiz, C., Parkkinen, L., & Révész, T. (2011) · doi:10.1002/9781444341256.ch23 · Cited by 1
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“This is in line with recent studies that have reported that tau staining is frequently associated with Lewy bodies and that α-synuclein assemblies can induce tau filament formation in vitro (67,68).”
Result
Neuropathology of Parkinson's disease
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Tetrahydroisoquinoline Neurotoxins in Parkinson Disease
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“Giasson and colleagues reported that α-synuclein could initiate polymerization of tau in vitro, and that tau significantly increased the assembly of α-synuclein into fibrils (Giasson et al 2003).”
Background
Multifaceted fibrils: self-assembly, polymorphism and functionalization
Sidhu, A. (2015) · doi:10.3990/1.9789036540247 · Cited by 1
Update on Parkinson's Disease Genetics
Krüger, R., Berg, D., Riess, O., & Riederer, P. (2007) · Springer eBooks · doi:10.1007/978-0-387-30377-2_3 · Cited by 1
BIOPHYSICAL STUDIES OF THE ALPHA-SYNUCLEIN PROTEIN ASSOCIATED WITH PARKINSON’S DISEASE AND OTHER SYNUCLEINOPATHIES
Apetri, M. M. (2006) · OhioLink ETD Center (Ohio Library and Information Network) · Cited by 1
Longevity factor klotho and resistance to cognitive deficits in a transgenic mouse model and in individuals with Parkinson’s diseasePreprint
Moreno, A. J., Luthra, N., Bonham, L. W., Lin, J. Y., Broestl, L., Bétourné, A., Sehgal, R., Wang, D., Lesné, S., Ostrem, J. L., et al. (2020) · Research Square · doi:10.21203/rs.3.rs-89525/v1 · Cited by 1
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Autosomal recessive, early-onset Parkinson’s disease
Bonifati, V. (2003) · RePub (Erasmus University Rotterdam)
Accumulation of Abnormally Processed Tau Protein in Neuronal Cells as a Biomarker for Dementia
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“Therefore, It was hypothesized that β-amyloid, αS, and tau protein promote the accumulation of each other [64], in recent years, there have been a number of studies that support this hypothesis.”
Result
Novel Proteins in α-Synucleinopathies
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Role of FKBPs in Parkinson’s Disease
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Authors: Giasson, B. I., Forman, M. S., Higuchi, M., Golbe, L. I., Graves, C. L., Kotzbauer, P. T., Trojanowski, J. Q., & Lee, V. M.-Y.
Affiliations: University of Medicine and Dentistry of New Jersey (US)
Corresponding author: Lee, Virginia M.-Y.
ORCID: Giasson, Benoit I.
Higuchi, Makoto
Golbe, Lawrence I.
Kotzbauer, Paul T.
Trojanowski, John Q.
Lee, Virginia M.-Y.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2003-04-25
Volume: 300
Issue: 5619
Pages: 636-640
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1082324
OpenAlex: W2073893553
Cited by: 879
References: 27
Citations by year: 2026: 23 · 2025: 29 · 2024: 37 · 2023: 35 · 2022: 58 · 2021: 32 · 2020: 50 · 2019: 52 · 2018: 49 · 2017: 42 · 2016: 35 · 2015: 31 · 2014: 39 · 2013: 42 · 2012: 33
FWCI: 26.70
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
Keywords: alpha-synuclein, tau protein, amyloid fibril formation, protein aggregation, neurodegenerative diseases, synucleinopathies, tauopathy, oligodendrocytes, P301L tau, A53T alpha-synuclein, transgenic mouse model, intraneuronal inclusions
MeSH terms: Amyloid, Animals, Biopolymers, Brain Chemistry, Humans, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Electron, Microscopy, Fluorescence, Nerve Tissue Proteins, Neurons, Oligodendroglia, Protein Conformation, Microscopy, Immunoelectron, tau Proteins, Neurodegenerative Diseases, Protein Isoforms, Tauopathies, Mice, Synucleins, alpha-Synuclein

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Initiation and Synergistic Fibrillization of Tau and Alpha-Synuclein

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