High cerebrospinal amyloid-β 42 is associated with normal cognition in individuals with brain amyloidosis

Background: Brain amyloidosis does not invariably predict dementia. We hypothesized that high soluble 42-amino acid beta amyloid (A beta 42) peptide levels are associated with normal cognition and hippocampal volume despite increasing brain amyloidosis. Methods: This cross-sectional study of 598 amyloid-positive participants in the Alzheimer's Disease Neuroimaging Initiative cohort examined whether levels of soluble A beta 42 are higher in amyloid-positive normal cognition (NC) individuals compared to mild cognitive impairment (MCI) and Alzheimer's disease (AD) and whether this relationship applies to neuropsychological assessments and hippocampal volume measured within the same year. All subjects were evaluated between June 2010 and February 2019. Brain amyloid positivity was defined as positron emission tomography-based standard uptake value ratio (SUVR) >= 1.08 for F-[18]-florbetaben or 1.11 for F-[18]-florbetapir, with higher SUVR indicating more brain amyloidosis. Analyses were adjusted for age, sex, education, APOE4, p-tau, t-tau, and centiloids levels. Findings: Higher soluble A beta 42 levels were observed in NC (864.00 pg/ml) than in MCI (768.60 pg/ml) or AD (617.46 pg/ml), with the relationship between NC, MCI, and AD maintained across all amyloid tertiles. In adjusted analysis, there was a larger absolute effect size of soluble A beta 42 than SUVR for NC (0.82 vs. 0.40) and MCI (0.60 vs. 0.26) versus AD. Each standard deviation increase in A beta 42 was associated with greater odds of NC than AD (adjusted odds ratio, 6.26; p < 0.001) or MCI (1.42; p = 0.006). Higher soluble A beta 42 levels were also associated with better neuropsychological function and larger hippocampal volume. Interpretation: Normal cognition and hippocampal volume are associated with preservation of high soluble A beta 42 levels despite increasing brain amyloidosis. (C) 2021 The Authors. Published by Elsevier Ltd.

Automated summary

The study found that high soluble Aβ42 levels are associated with normal cognition and hippocampal volume despite increasing brain amyloidosis, suggesting that preserving high soluble Aβ42 levels could be important for maintaining cognitive function and hippocampal health.