Leptin levels are associated with body mass index and Alzheimer's disease in Down syndrome

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INTRODUCTION: Higher body mass index (BMI) is linked to greater risk of Alzheimer's disease (AD) and elevated plasma leptin levels correlate with cognitive decline and AD. Since obesity is a frequent feature in individuals with Down syndrome (DS), we investigated the association between obesity, the leptin pathway, and AD neuropathology in people with DS. METHODS: Plasma concentrations of leptin and AD biomarkers were measured in 40 individuals (aged controls, Down syndrome and Alzheimer's disease [DSAD], and AD participants). Frontal cortex leptin, leptin receptors (LepRs), and leptin-associated proteins were measured in 73 individuals with DS, DSAD, and AD, and compared to age-matched controls using immunohistochemistry. RESULTS: Individuals with DSAD had the highest plasma leptin levels, as well as the highest leptin resistance index and brain leptin deficiency. Plasma leptin levels were significantly associated with staging of AD neuropathology. DISCUSSION: Leptin has the potential to be an early indicator and therapeutic target for AD in people with and without DS. HIGHLIGHTS: Plasma leptin levels are increased in Down syndrome and Alzheimer's disease (DSAD). Leptin resistance and brain leptin deficiency are present in Down syndrome (DS) and DSAD. Plasma leptin levels are positively associated with staging of Alzheimer's disease (AD) neuropathology.

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