title: Relation between insulin, insulin-related factors, and plasma amyloid beta peptide levels at midlife in a population-based study.
abstract: Little is known regarding factors associated with soluble amyloid beta peptide (Aβ) concentrations in humans at late midlife, when Aβ is likely most critical to Alzheimer disease pathogenesis. We examined the association between insulin, insulin-related factors, and plasma Aβ at late midlife. Plasma Aβ42, Aβ40, fasting insulin, and c-peptide were measured in 468 women without diabetes, aged 59 to 69 years (median 63 y). Before blood draw, participants reported body mass index, waist circumference, physical activity, alcohol intake, hypertension, and diabetes family history. Linear regression was used to calculate age-adjusted mean differences in Aβ42 to Aβ40 ratio, and Aβ42 levels, by insulin and insulin-related factors. The ratio of Aβ42 to Aβ40 was statistically significantly lower in women with family history of diabetes, and Aβ42 was significantly lower with less physical activity, greater waist circumference, hypertension, and family history of diabetes (P<0.05 for all). Aβ42 to Aβ40 ratio, and Aβ42 levels, appeared lower with higher c-peptide levels (P trend=0.07 and 0.06, respectively), although these were not statistically significant. In summary, insulin-related factors appear associated with lower plasma Aβ42 to Aβ40 ratio, and Aβ42, at late midlife, consistent with increased brain sequestration of Aβ42 (relative to Aβ40), suggesting insulin merits focus in strategies to prevent dementia.
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. nhmkt@channing.harvard.edu
authors.forename: Mary K
authors.initials: MK
authors.lastname: Townsend
authors.forename: Olivia I
authors.initials: OI
authors.lastname: Okereke
authors.forename: Weiming
authors.initials: W
authors.lastname: Xia
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Selkoe
authors.forename: Francine
authors.initials: F
authors.lastname: Grodstein
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000097:blood* / Q000378:metabolism; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood*; D005215:Fasting / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood
chemical_list: D016229:Amyloid beta-Peptides; D002096:C-Peptide; D007328:Insulin; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C050920:insulin-related factor