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

Abstract

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.

Measurement of CSF α‐synuclein improves early differential diagnosis of mild cognitive impairment due to Alzheimer’s disease

“…These data are in good agreement with other data from previous studies (Korff et al ; Toledo et al ; Mackin et al ; Slaets et al ; Chiasserini et al ; Shi et al ). Interestingly, in a recent study, a trend of increased CSF α‐syn levels was determined in individuals with subjective complaints of memory dysfunction together with evidence of cerebral deposition of Aβ, compared with Aβ PET (positron emission tomography)‐negative subjects, suggesting an association of CSF α‐syn with AD‐related pathophysiological mechanisms at preclinical phases of the disease (Vergallo et al ). Increased CSF α‐syn levels have been confirmed in AD autopsy‐confirmed cases, discriminating between dementia with Lewy bodies and Alzheimer's disease (Mollenhauer et al ).…”

“…The increase of CSF α‐syn levels in AD patients relies on evidence of over‐expression in the brain tissue and/or on the neuronal damage and release of α‐syn into the brain’s interstitial fluid and then into the CSF (Majbour et al ). These changes in α‐syn expression should indicate a role in AD pathogenesis (Korff et al ; Vergallo et al ).…”

CSF total tau/α-synuclein ratio improved the diagnostic performance for Alzheimer’s disease as an indicator of tau phosphorylation

“…1 c), indicating its potential as a prognostic biomarker. In previous studies, α-syn showed a positive association with brain amyloid beta deposition in the cognitively normal subject with memory complain and was the highest level in patients with MCI, suggesting the involvement of α-syn from the early stage of AD [ 20 , 35 ]. In view of all findings, α-syn might play a role with the association of amyloid beta deposition from the preclinical stage of AD and could improve prognostic and diagnostic performance as a biomarker in AD.…”

“…The incorporation of new biomarkers, such as α-syn or TDP-43, should be demanded, as there were limitations to distinguish and to interpret similar neurodegenerative disorders [16]. Interestingly, CSF α-syn had a strong positive correlation with CSF tau in AD [17][18][19][20]. Other studies reported that the levels of α-syn in CSF tended to increase in AD compared to healthy control (HC) [17][18][19][21][22][23][24][25][26].…”

Fluid Candidate Biomarkers for Alzheimer’s Disease: A Precision Medicine Approach

“…Moreover, serum NFL could help in the differentiation of Primary Progressive Aphasia (PPA) variants. Indeed, serum NFL is increased in PPA compared to controls and discriminates between nfvPPA/svPPA (with a more likely FTD pathology) and lvPPA (where an AD pathology is expected in more than 50% of cases) with 81% and 67% of sensitivity and specificity, respectively [230].…”