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Association of APOE-ε4 and GAP-43-related presynaptic loss with β-amyloid, tau, neurodegeneration, and cognitive decline.
- Source :
-
Neurobiology of Aging . Dec2023, Vol. 132, p209-219. 11p. - Publication Year :
- 2023
-
Abstract
- Apolipoprotein E-ε4 (APOE-ε4) carriers had elevated cerebrospinal fluid (CSF) presynaptic protein growth-associated protein-43 (GAP-43), but the underlying mechanism is not fully understood. We investigated how the APOE-ε4 genotype affects the baseline and longitudinal changes in CSF GAP-43 and their associations with β-amyloid positron emission tomography (Aβ PET), CSF phosphorylated tau 181 (p-Tau 181), neurodegeneration, and cognitive decline. Compared to APOE-ε4 non-carriers, APOE-ε4 carriers had higher baseline levels and faster rates of increases in Aβ PET, CSF p-Tau 181 , and CSF GAP-43. Both higher baseline levels and faster rates of increase in CSF GAP-43 were associated with greater baseline Aβ PET and CSF p-Tau 181 , which fully mediated the APOE-ε4 effect on CSF GAP-43 elevations. Independent of Aβ PET and CSF p-Tau 181 , APOE-ε4 carriage was associated with exacerbated GAP-43-related longitudinal hippocampal atrophy and cognitive decline, especially in Aβ+ participants (GAP-43 × time × APOE-ε4). These findings suggest that the APOE-ε4 effect on GAP-43-related presynaptic dysfunction is mediated by primary Alzheimer's pathologies and independently correlates to hippocampal atrophy and cognitive decline in the future. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01974580
- Volume :
- 132
- Database :
- Academic Search Index
- Journal :
- Neurobiology of Aging
- Publication Type :
- Academic Journal
- Accession number :
- 173343614
- Full Text :
- https://doi.org/10.1016/j.neurobiolaging.2023.09.012