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High Soluble Amyloid-β(42) Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer’s Disease-Causing Mutations
BACKGROUND: In amyloid-positive individuals at risk for Alzheimer’s disease (AD), high soluble 42-amino acid amyloid-β (Aβ(42)) levels are associated with normal cognition. It is unknown if this relationship applies longitudinally in a genetic cohort. OBJECTIVE: To test the hypothesis that high Aβ(4...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9661329/ https://www.ncbi.nlm.nih.gov/pubmed/36120786 http://dx.doi.org/10.3233/JAD-220808 |
Sumario: | BACKGROUND: In amyloid-positive individuals at risk for Alzheimer’s disease (AD), high soluble 42-amino acid amyloid-β (Aβ(42)) levels are associated with normal cognition. It is unknown if this relationship applies longitudinally in a genetic cohort. OBJECTIVE: To test the hypothesis that high Aβ(42) preserves normal cognition in amyloid-positive individuals with Alzheimer’s disease (AD)-causing mutations (APP, PSEN1, or PSEN2) to a greater extent than lower levels of brain amyloid, cerebrospinal fluid (CSF) phosphorylated tau (p-tau), or total tau (t-tau). METHODS: Cognitive progression was defined as any increase in Clinical Dementia Rating (CDR = 0, normal cognition; 0.5, very mild dementia; 1, mild dementia) over 3 years. Amyloid-positivity was defined as a standard uptake value ratio (SUVR) ≥1.42 by Pittsburgh compound-B positron emission tomography (PiB-PET). We used modified Poisson regression models to estimate relative risk (RR), adjusted for age at onset, sex, education, APOE4 status, and duration of follow-up. The results were confirmed with multiple sensitivity analyses, including Cox regression. RESULTS: Of 232 mutation carriers, 108 were PiB-PET-positive at baseline, with 43 (39.8%) meeting criteria for progression after 3.3±2.0 years. Soluble Aβ(42) levels were higher among CDR non-progressors than CDR progressors. Higher Aβ(42) predicted a lower risk of progression (adjusted RR, 0.36; 95% confidence interval [CI], 0.19–0.67; p = 0.002) better than lower SUVR (RR, 0.81; 95% CI, 0.68–0.96; p = 0.018). CSF Aβ(42) levels predicting lower risk of progression increased with higher SUVR levels. CONCLUSION: High CSF Aβ(42) levels predict normal cognition in amyloid-positive individuals with AD-causing genetic mutations. |
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