P3‐030: The relation between insulin, insulin‐related factors, and plasma amyloid‐beta protein levels at mid‐life in a large‐scale population‐based study
Year: 2010
Type: article
Study design: Observational Study
Abstract: The accumulation of amyloid beta (Abeta) peptides into oligomers and diffuse plaques appears to be an initial step leading to dementia. Yet, little is known regarding risk factors associated with soluble Abeta concentrations. Several lines of evidence suggest that insulin may influence Abeta levels. Thus, we examined the cross-sectional associations between insulin, insulin-related factors, and plasma Abeta levels at late mid-life, likely the point at which Abeta accumulation is most important, among women in the Nurses' Health Study. We measured plasma levels of Abeta40 and Abeta42 by ELISA in 481 women aged 58-69 years at the time of blood draw (1989-1990). Women with diabetes were excluded to reduce confounding by diabetes or diabetes-related complications. Measurements of fasting plasma insulin and c-peptide, a measure of insulin secretion, were also obtained. Participants provided information on body mass index (BMI), waist circumference, physical activity, alcohol intake, high blood pressure, and family history of diabetes on biennial questionnaires administered from 1976 to 1990. We used linear regression to calculate age-adjusted mean differences in Abeta42 and Abeta42:Abeta40 ratio according to levels of insulin and insulin-related factors. The plasma Abeta42:Abeta40 ratio was significantly lower among women in the highest versus the lowest quartile of plasma c-peptide (p = 0.049), consistent with the hypothesized relation between increased insulin secretion and increased deposition of soluble Abeta42 (relative to Abeta40) into insoluble plaques in the brain. Similarly, Abeta42:Abeta40 ratio was lower among women with a family history of diabetes (p = 0.04), and levels of circulating Abeta42 were lower among women with higher BMI (p trend = 0.06), higher alcohol intake (p trend = 0.06), high blood pressure (p = 0.01), and a family history of diabetes (p = 0.02). Higher physical activity, which improves insulin resistance, was associated with higher levels of circulating Abeta42 (p trend = 0.04), possibly indicating less deposition of soluble Abeta42 into insoluble plaques. Insulin secretion and several other insulin-related factors appear to influence plasma levels of Abeta at mid-life. This is strong evidence, from a large population-based study, that insulin levels are one factor involved in early stages of Abeta accumulation, and merit continued research as part of strategies to prevent dementia.
Source: Alzheimer s & Dementia
Institutions: Harvard University, Brigham and Women's Hospital
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2029782064