Abstract Details

Title Circulating Leptin in the Preclinical Stage of Alzheimer’s Disease

Topic Aging and Dementia

Presentation(s) N4 - Neuroscience in the Clinic: The Neurology of Obesity (4:30 PM-4:45 PM)

Poster/Presentation
Number 001

Background Weight loss is an early manifestation of AD that can precede the cognitive decline. Leptin is an adipocyte-derived hormone that is essential for regulating body weight. However, it is not known if leptin signaling is altered in individuals during the preclinical stage of AD, where there is Aβ and tau pathology but no significant cognitive decline.

Objective To determine if circulating leptin levels are altered in preclinical Alzheimer’s Disease (AD).

Design/Methods Cognitively normal (Clinical Dementia Rating of 0) volunteers from two cohorts, 156 subjects (58% female) from St. Louis and 28 subjects (50% female) from Atlanta, with fasting plasma and cerebrospinal fluid (CSF) samples were included in this cross-sectional study. Preclinical AD was defined by previously established CSF criteria. Plasma leptin was measured by ELISA (R&D Systems).

Results St. Louis Cohort: In males, plasma leptin was significantly lower in preclinical AD compared to controls (control: 3.97 ± 1.61 ng/mL; preclinical AD: 2.83 ± 1.18 ng/mL, p=0.006). Plasma leptin was associated with CSF Aβ42 (β=0.41, p=0.001) but not CSF tau or p-tau₁₈₁ (all p>0.05). In females, there was no significant difference in plasma leptin levels between preclinical AD and controls (p>0.05). Atlanta cohort: In males, there was a trend towards lower plasma leptin levels in preclinical AD compared to controls (p=0.17). In females, there was an insufficient number of preclinical AD subjects for analysis. Secondary analysis in this cohort showed that African Americans have significantly higher plasma leptin levels than Caucasians, suggesting leptin resistance may be a confounding factor for African Americans.

Conclusions These results suggest that alterations in leptin signaling may be caused by early Aβ pathology. Although these findings need verification in additional sufficiently powered cohorts and the mechanisms defined including any differences due to sex and race, these findings may provide key insights into the mechanisms underlying weight loss early in AD.

Authors/Disclosures
Carrie Sha PRESENTER	Ms. Sha has nothing to disclose.
William T. Hu, MD, PhD, FAAN (Rutgers Biomedical and Health Sciences)	Dr. Hu has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Fujirebio. Dr. Hu has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Beckman Coulter. Dr. Hu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Apellis Pharmaceuticals. The institution of Dr. Hu has received research support from NIA. The institution of Dr. Hu has received research support from TMCity Foundation. The institution of Dr. Hu has received research support from Atlanta Family Foundation. The institution of Dr. Hu has received research support from Fujirebio Diagnostics.
Costantino Iadecola, MD (Weill Cornell Medicine)	Dr. Iadecola has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Broadview Ventures.
Makoto Ishii, MD, PhD (University of Texas Southwestern Medical Center)	Dr. Ishii has stock in Regeneron Pharmaceuticals. The institution of Dr. Ishii has received research support from NIH. The institution of Dr. Ishii has received research support from BrightFocus Foundation. The institution of Dr. Ishii has received research support from Alzheimer's Association. Dr. Ishii has received personal compensation in the range of $0-$499 for serving as a Author/Contributor with Relias Media.

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