Premium
P3‐239: PLASMA LEPTIN, ADIPONECTIN AND THE LEPTIN:ADIPONECTIN RATIO IN COGNITIVELY NORMAL SUBJECTS WITH PRECLINICAL ALZHEIMER'S DISEASE
Author(s) -
Ishii Makoto,
Iadecola Costantino
Publication year - 2018
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.2018.06.1598
Subject(s) - adiponectin , leptin , medicine , endocrinology , adipokine , body mass index , disease , hormone , adipocyte , neurology , amyloid beta , obesity , adipose tissue , insulin resistance , psychiatry
Background:Accumulating evidence from epidemiological studies suggests that body weight and systemic metabolic deficits can occur before the cognitive decline in Alzheimer’s disease (AD) (Ishii, M. and Iadecola C., Cell Metabolism 22:761,2015). Our studies using mouse models found that amyloid-beta pathology can cause hypothalamic dysfunction that was associated with low body adiposity and low plasma leptin levels prior to significant cognitive decline or plaque formation (Ishii, M. et al., J Neuroscience 34:9096,2014). However, it has not been established if adipocyte hormones are similarly altered in humans with preclinical AD. Methods: In this cross-sectional study, community dwelling cognitively normal male subjects from the Healthy Aging & Senile Dementia and Adult Children Study (Missouri, USA) with body mass index <30 were classified as preclinical AD (n1⁄420) or biomarker negative controls (n1⁄445) using previously established CSF criteria (Vos, S. et al., Lancet Neurology 12:957,2013). Plasma levels of leptin, total adiponectin, and high molecular weight (HMW) adiponectin were quantified by enzyme-linked immunosorbent assays. Since decreasing adiposity correlates with decreasing plasma leptin levels and increasing plasma adiponectin levels (Ishii, M. and Iadecola C., Biochmica et Biophysica Acta Molecular Basis of Disease 1862:966,2016), the leptin:adiponectin ratio was used as an index of adiposity. Multiple linear regression analysis was used to examine correlations between plasma adipocyte hormones (levels and ratios) and preclinical AD status, adjusting for age. Results: Mean plasma leptin levels were significantly lower in preclinical AD subjects compared to controls and were significantly associated with preclinical AD status (p1⁄40.005). Conversely, compared to control subjects, mean plasma levels of total adiponectin and HMW adiponectin were both significantly higher in preclinical AD subjects, but neither total nor HMW adiponectin levels were associated with preclinical AD status (p>0.05). Finally, the mean leptin:adiponectin ratio was significantly lower in preclinical AD subjects compared to controls and was significantly associated with preclinical AD status (p1⁄40.033). Conclusions:Although these findings need verification in additional cohorts, our studies suggest that early AD pathology can cause alterations in adipocyte hormones related to body weight and metabolism. Future longitudinal studies will help determine the diagnostic and prognostic utility of these measures. Funding: BrightFocus Foundation (MI), AG051179 (MI), NS37853 (CI).