Insulin-like growth factor-1 and risk of late-onset Alzheimer's disease: findings from a family study.
Insulin-like growth factor-1 (IGF-1), part of an evolutionary conserved signaling pathway in both mammalian and non-mammalian species, is inferred in neurodegenerative disorders including Alzheimer's disease (AD). A murine model for AD shows that reduced IGF-1 signaling prevents AD-like characteristics. However, variation in serum levels of IGF-1 and risk of AD in humans has yet to be determined. We used a proven family design, comparing middle-aged offspring with and without a parental history of AD. The offspring under study carry an increased risk of AD but do not yet experience cognitive impairment. A total of 206 offspring from 92 families with a parental history of AD were compared with 200 offspring from 97 families without a parental history of AD. Apolipoprotein-E (APOE) genotypes and serum IGF-1 levels were compared in subjects with and without a parental history of AD using linear regression, adjusted for APOE genotype and other possible demographic and clinical confounders. Offspring with a parental history of AD were more likely to be an APOE ε4 allele carrier (46.5% vs. 21%, p = 0.001) than were offspring without such a parental history. Offspring with a parental history of AD had higher IGF-1 levels than subjects without such a history, in both unadjusted and adjusted analyses (18.3 mmol/L vs. 16.7 mmol/L, p = 0.001). In conclusion, higher serum IGF-1 levels in middle age are associated with risk of AD disease in older age, independent of APOE genotype.
Department of Psychiatry, VU University Medical Center/GGZinGeest, Amsterdam, the Netherlands; EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands. Electronic address: e.vexel@vumc.nl.
E
E
van Exel
P
P
Eikelenboom
H
H
Comijs
D J H
DJ
Deeg
M L
ML
Stek
R G J
RG
Westendorp
D017668:Age of Onset; D000544:Alzheimer Disease / Q000097:blood* / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D012306:Risk; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D001057:Apolipoproteins E; D007334:Insulin-Like Growth Factor I
Alzheimer's disease; Family study; Insulin-like growth factor–1