High Soluble Amyloid-β42 Predicts Normal Cognition in Amyloid-Positive Individuals with Alzheimer's Disease-Causing Mutations
| Autor: | Sturchio, Andrea, Dwivedi, Alok K, Nuebling, Georg Sebastian Otto, El Andaloussi, Samir, Svenningsson, Per, Ezzat, Kariem, Espay, Alberto J, Consortia, Dominantly Inherited Alzheimer, Malm, Tarja, Wood, Matthew J A, Cilia, Roberto, Sharma, Jennifer S, Hill, Emily J, Schneider, Lon S, Graff-Radford, Neill R, Mori, Hiroshi |
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| Rok vydání: | 2022 |
| Předmět: |
cognition
diagnostic imaging [Cognitive Dysfunction] genetics [Alzheimer Disease] genetics [Mutation] tau Proteins cerebrospinal fluid [Amyloid beta-Peptides] amyloid-β Cognition atrophy genetics [Dementia] Alzheimer Disease Humans Cognitive Dysfunction ddc:610 cerebrospinal fluid [Peptide Fragments] FDG-PET Amyloid beta-Peptides methods [Positron-Emission Tomography] genetics [Cognitive Dysfunction] Amyloidosis Peptide Fragments cerebrospinal fluid [Alzheimer Disease] cerebrospinal fluid [Cognitive Dysfunction] cerebrospinal fluid [tau Proteins] cerebrospinal fluid [Biomarkers] Positron-Emission Tomography Mutation Dementia diagnostic imaging [Alzheimer Disease] Alzheimer’s disease Biomarkers |
| Zdroj: | Journal of Alzheimer's disease 90(1), 333-348 (2022). doi:10.3233/JAD-220808 |
| ISSN: | 1875-8908 |
| DOI: | 10.3233/JAD-220808 |
| Popis: | In amyloid-positive individuals at risk for Alzheimer's disease (AD), high soluble 42-amino acid amyloid-β (Aβ42) levels are associated with normal cognition. It is unknown if this relationship applies longitudinally in a genetic cohort.To test the hypothesis that high Aβ42 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).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.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 Aβ42 levels were higher among CDR non-progressors than CDR progressors. Higher Aβ42 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 Aβ42 levels predicting lower risk of progression increased with higher SUVR levels.High CSF Aβ42 levels predict normal cognition in amyloid-positive individuals with AD-causing genetic mutations. |
| Databáze: | OpenAIRE |
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