Association of cerebrospinal fluid α‐synuclein with total and phospho‐tau181 protein concentrations and brain amyloid load in cognitively normal subjective memory complainers stratified by Alzheimer's disease biomarkers
Open accessAbstract
Introduction: Several neurodegenerative brain proteinopathies, including Alzheimer's disease (AD), are associated with cerebral deposition of insoluble aggregates of α‐synuclein. Previous studies reported a trend toward increased cerebrospinal fluid (CSF) α‐synuclein (α‐syn) concentrations in AD compared with other neurodegenerative diseases and healthy controls. Methods: The pathophysiological role of CSF α‐syn in asymptomatic subjects at risk of AD has not been explored. We performed a large‐scale cross‐sectional observational monocentric study of preclinical individuals at risk for AD (INSIGHT‐preAD). Results: We found a positive association between CSF α‐syn concentrations and brain β‐amyloid deposition measures as mean cortical standard uptake value ratios. We demonstrate positive correlations between CSF α‐syn and both CSF t‐tau and p‐tau 181 concentrations. Discussion: Animal models presented evidence, indicating that α‐syn may synergistically and directly induce fibrillization of both tau and β‐amyloid. Our data indicate an association of CSF α‐syn with AD‐related pathophysiological mechanisms, during the preclinical phase of the disease.
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In mild cognitive impairment patients who progressed to Alzheimer's disease over 24 months, there is a dose-response relationship between the APOEε4 allele and cerebrospinal fluid αSyn levels, with APOEε4 homozygous carriers exhibiting the highest cerebrospinal fluid αSyn concentrations.
“we documented a dose-response relationship between the APOEε4 allele and CSF αSyn levels where APOEε4 homozygous carriers exhibited the highest CSF αSyn concentrations [26].”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [26]
A relationship between brain amyloid-β load and cerebrospinal fluid αSyn levels was previously proposed by Vergallo and co-authors in cognitively normal individuals with subjective memory complaints stratified by Alzheimer's disease biomarkers.
“A relationship between brain Aβ load and CSF αSyn levels was previously proposed by Vergallo and co-authors who examined cognitively normal individuals with subjective memory complaints stratified by AD biomarkers [26].”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [26]
CSF αSyn is positively correlated with CSF t-tau and p-tau.
“CSF αSyn positively correlated to CSF t-tau and p-tau”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as Vergallo et al. 2018 [26]
Increased CSF αSyn is associated with increased brain Aβ deposition.
“Increased CSF αSyn associated with increased brain Aβ deposition”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as Vergallo et al. 2018 [26]
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References 37 · Cited by 59
- Authors
- Vergallo, A., Bun, R., Toschi, N., Baldacci, F., Zetterberg, H., Blennow, K., Cavedo, E., Lamari, F., Habert, M., Dubois, B., Floris, R., Garaci, F., Lista, S., Hampel, H., INSIGHT‐preAD study group, & (APMI), F. T. L. P. M. I.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of Rome Tor Vergata (IT)
- University of Pisa (IT)
- Sahlgrenska University Hospital (SE)
- Assistance Publique – Hôpitaux de Paris (FR)
- Corresponding author
- Vergallo, Andrea
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2018-07-25
- Volume
- 14
- Issue
- 12
- Pages
- 1623-1631
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W2883052156
- Cited by
- 59
- References
- 37
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 7 · 2021: 12 · 2020: 11 · 2019: 14 · 2018: 3
- FWCI
- 6.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, other-oa)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- HAL (submittedVersion, other-oa)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion, cc-by-nc-nd)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Funders
- Rotary Foundation (GG1758249)
- Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- tau phosphorylation
- MeSH terms
- Aged, Alzheimer Disease, Amyloid, Brain, Cognition, Cross-Sectional Studies, Female, Humans, Male, Memory Disorders, Cohort Studies, Biomarkers, tau Proteins, Positron-Emission Tomography, alpha-Synuclein, Apolipoprotein E4, Diagnostic Self Evaluation, Prodromal Symptoms
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