Lower Plasma Amyloid-Beta Levels Associated with Risk of Dementia

by | Nov 26, 2019 | 2018, Alzheimer's Disease, Brain Health

Written by Angeline A. De Leon, Staff Writer. This study provides evidence that lower plasma Aβ levels, specifically Aβ1–38 and Aβ1–42, are associated with an increased risk of dementia, specifically Alzheimer’s disease.

agingDementia is associated with the accumulation of amyloid plaques (Aβ, aggregates of misfolded protein forming in spaces between neurons) in the brain 1. However, for Aβ1-40 and Aβ1-42 peptides, specifically, the literature suggests inconsistent findings: whereas some studies report a link between higher plasma levels of Aβ1-40 and Aβ1-42 and worse cognitive function 2,3, others indicate increased Aβ1-40 and Aβ1-42 concentrations are associated with reduced risk of dementia 4,5. Other investigations also demonstrate a relationship between risk of Alzheimer’s disease (AD) and circulating levels of Aβ1-42, but not Aβ1-40 6,7. Thus, although there appears to be a general relationship between plasma Aβ and risk of dementia, the exact nature of the association is unclear and may depend on other factors, such as the stage of the neurodegenerative disease 8. Along with Aβ1-40 and Aβ1-42, recent work has discovered a more novel isoform, Aβ1-38, to be a sensitive biomarker for differential diagnosis of dementia 9. In a 2018 study 10 published in Alzheimer’s Research and Therapy, investigators explored the relationship between plasma levels of Aβ1-40, Aβ1-42, and Aβ1-38 and preclinical markers of neurodegeneration and risk of dementia in a population of middle-aged and older adults.

A total of 458 individuals (mean age= 67.8 years) were enrolled in a prospective, population-based cohort study. At baseline, blood samples were drawn and plasma levels of Aβ1-40, Aβ1-42, and Aβ1-38 were quantified using plasma enzyme-linked immunosorbent assays. Participants underwent a brain imaging scan, from which gray matter, white matter, and hippocampal brain volumes were calculated. At baseline and at follow-up, subjects were administered the Mini Mental State Examination and the Geriatric Mental State Schedule and were monitored continuously over a 15-year period for symptoms of dementia. Dementia was diagnosed by a neurologist using the Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised, and AD was diagnosed based on internationally accepted criteria.

At baseline, mean values of plasma Aβ1-38, Aβ1-40, and Aβ1-42 were 19.4 +/- 4.3, 186.1 +/- 35.9, and 56.3 +/- 6.2 pg/ml, respectively. A significant association was found between lower levels of plasma Aβ1-42 and smaller hippocampal volume (mean difference in hippocampal volume per SD decrease in Aβ1-42 levels = -0.13, 95% Confidence Interval: -0.23 to –0.04, p = 0.007). At mean follow-up (14.8 years), 79 cases of dementia were documented, 64 of which were AD and 15 of which were vascular dementia. After controlling for confounding variables, multivariate analyses revealed that lower levels of Aβ1-38 and Aβ1-42 were linked to higher risk of dementia: Hazard Ratio per SD decrease in Aβ1-38 = 1.33, 95% CI: 1.01 to 1.89; HR per SD decrease in Aβ1-42 = 1.27, 95% CI: 1.02 to 1.58. Lower levels of Aβ1-38 and Aβ1-42 were also specifically associated with increased risk of AD: HR per SD decrease in Aβ1-38 = 1.39, 95% CI: 1.00 to 2.16; HR per SD decrease in Aβ1-42 = 1.35, 95% CI: 1.05 to 1.75.

Evidence from the study indicates a relationship between plasma Aβ levels and risk of dementia, such that lower concentrations of Aβ1-38 and Aβ1-42 appear to be associated with higher risk of dementia, specifically AD. Lower levels of Aβ1-42 were also linked to smaller hippocampal volume, suggesting that the Aβ1-42 peptide may be involved in cortical atrophy. Current findings also support the utility of the novel Aβ1-38 isoform as a potential biomarker of dementia. Further investigation is warranted to elucidate how Aβ1-38 and Aβ1-42 might lead to dementia through different pathways and to determine how Aβ pathology relates to other subtypes of dementia. Potential study limitations involve the lack of in vivo analysis of Aβ burden and measurement of Aβ concentrations at a single time point vs. repeated measures over time.

Source: Hilal, Saima, Frank J. Wolters, Marcel M. Verbeek, Hugo Vanderstichele, M. Kamran Ikram, Erik Stoops, M. Arfan Ikram, and Meike W. Vernooij. “Plasma amyloid-β levels, cerebral atrophy and risk of dementia: a population-based study.” Alzheimer’s research & therapy 10, no. 1 (2018): 63.

© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), (http://creativecommons.org/publicdomain/zero/1.0/)

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Posted November 26, 2019.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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