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Very low levels of ABCA7 in the cerebrum and Alzheimer’s disease onset between the ages of 60 and 80 independently of APOE
Ist Teil von
Journal of neuropathology and experimental neurology, 2024-10, Vol.83 (10), p.808-821
Ort / Verlag
England: Oxford University Press
Erscheinungsjahr
2024
Quelle
Oxford Journals 2020 Medicine
Beschreibungen/Notizen
Abstract
This cross-sectional study addressed the ABCA7-Alzheimer’s disease (AD) association. ABCA7 protein levels were quantified in 3 cerebral regions of brain donors with Braak neurofibrillary tangle (NFT) stages 0-V. Ordinal regression models were implemented to estimate the effect of ABCA7 on stopping in an earlier Braak NFT stage versus progressing to the later stages in 2 prespecified age segments. In the final model, high ABCA7 levels in the parietal cortex increased the odds of remaining cognitively healthy (ie, in stages 0/I) versus experiencing AD onset (ie, progressing to stages II-V) in the 61-80 age segment (OR = 2.87, adj 95% CI = 1.41-7.86, adj P = .007, n = 109), after controlling for APOE and other covariates. No ABCA7-AD association was found in the 81-98 age segment (n = 113). Parietal ABCA7 levels in 61-80-year-old with stages II-V were very low, even significantly lower than in 81-98-year-old with stages II-V. ABCA7 levels in the prefrontal cortex and hippocampus predicted AD onset in the 61-80 age segment after adjustment for APOE. ABCA7 levels were also the lowest in 61-80-year-old with frequent neuritic plaques. Thus, very low ABCA7 levels in the cerebrum are associated with AD onset in the 7th-8th decade of life.