Premium
P2‐023: Vitamin D receptor polymorphisms and Alzheimer disease
Author(s) -
Robin Hsiung Ging-Yuek,
Fok Alice,
Pettersen Jacqueline A.
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.06.559
Subject(s) - calcitriol receptor , medicine , single nucleotide polymorphism , vitamin d and neurology , cohort , dementia , genotype , genotyping , logistic regression , population , oncology , disease , biology , genetics , gene , environmental health
Background:The relationship between genetic Alzheimer’s disease (AD) risk and insulin resistance remains uncertain. Methods: The goal of this project was to characterize glucose metabolism in a large cohort of well-characterized individuals (n1⁄4331) with either no dementia (ND) or cognitive impairment due to probable Alzheimer’s disease (AD) and examine the relationship between insulin resistance and genotype. Samples were characterized for fasting glucose, fasting insulin, and apolipoprotein E. All analyses were controlled for age, sex, and education. Results: Subjects with AD exhibited higher fasting insulin (8.1 mU/mL [6.1]), compared to ND subjects (6.9mU/mL [6.2], p1⁄40.04). ND subjects were more insulin sensitive when assessed using the quantitative insulin sensitivity check index (0.39 [0.07] vs 0.37 [0.06] p1⁄40.05). We also observed interesting relationships between apolipoprotein E (ApoE) genotype and fasting insulin. ApoE e4 carriers exhibited significantly lower fasting insulin levels than APOE e3/e3 subjects in both diagnosis groups (ND: e3/e3 0.71 [0.4] vs e4 carriers 0.59 [0.4], AD: e3/e3 0.88 [0.4] vs e4 carriers 0.72 [0.4], (p1⁄40.02)). When subjects were grouped by global clinical dementia rating, APOE e3/e3 subjects with increasing CDR global score exhibited a stepwise increase in fasting insulin levels, while APOE e4 carriers exhibited a stepwise increase only to the level of CDR 1⁄41, before fasting insulin levels drastically dropped in the most severely affected subjects. Conclusions: These analyses suggest a relationship between ApoE genotype and compensatory increases in insulin levels with AD diagnosis and progression.