Associations between misfolded alpha-synuclein aggregates and Alzheimer's disease pathology in vivo.
Alzheimers Dement
; 2024 Sep 11.
Article
en En
| MEDLINE
| ID: mdl-39258841
ABSTRACT
INTRODUCTION:
We examined the relations of misfolded alpha synuclein (α-synuclein) with Alzheimer's disease (AD) biomarkers in two large independent cohorts.METHODS:
We included Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably Two (BioFINDER-2) and Alzheimer's Disease Neuroimaging Initiative (ADNI) participants (n = 2315, cognitively unimpaired, mild cognitive impairment, AD dementia) who had cross-sectional cerebrospinal fluid (CSF) α-synuclein measurement from seed-amplification assay as well as cross-sectional and longitudinal amyloid beta (Aß) and tau levels (measured in CSF and/or by positron emission tomography). All analyses were adjusted for age, sex, and cognitive status.RESULTS:
Across cohorts, the main biomarker associated with α-synuclein positivity at baseline was higher levels of Aß pathology (all p values ≤ 0.02), but not tau. Looking at longitudinal measures of AD biomarkers, α-synuclein -positive participants had a statistically significant faster increase of Aß load, although of modest magnitude (1.11 Centiloid/year, p = 0.02), compared to α-synuclein -negative participants in BioFINDER-2 but not in ADNI.DISCUSSION:
We showed associations between concurrent misfolded α-synuclein and Aß levels, providing in vivo evidence of links between these two molecular disease pathways in humans. HIGHLIGHTS Amyloid beta (Aß), but not tau, was associated with alpha-synuclein (α-synuclein) positivity. Such association was consistent across two cohorts, beyond the effect of age, sex, and cognitive status. α-synuclein-positive participants had a small, statistically significant faster increase in Aß positron emission tomography levels in one of the two cohorts.
Texto completo:
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Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Alzheimers Dement
Año:
2024
Tipo del documento:
Article
País de afiliación:
Suecia
Pais de publicación:
Estados Unidos