Plasma Leptin Is Associated With Amyloid CSF Biomarkers and Alzheimer's Disease Diagnosis in Cognitively Impaired Patients

Abstract

Background: Metabolic dysfunction and dysregulation of leptin signaling have been linked to Alzheimer's disease (AD)'s pathophysiology. The objectives of this study were to examine the associations between plasma leptin, cerebrospinal fluid (CSF), beta-amyloid (Aβ), and tau biomarkers (AT[N] status) and with the stage of cognitive impairment.

Methods: Cross-sectional analysis of data from cognitively impaired patients from a tertiary memory clinic. Plasma leptin levels were compared according to the stage of cognitive impairment and biomarker profiles, using the AT(N) classification. Linear regression models were performed to examine the relationship between leptin and CSF biomarkers. Results were adjusted for age, gender, body mass index (BMI), and APOE ε4. In a subgroup of A+T+ individuals, we compared the 2-year evolution of Mini-Mental State Examination scores, according to the participants' tertile of plasma leptin levels.

Results: We included 1 036 participants (age 68.7 ± 9.1, females = 54.1%). A+T+ and A+T- patients had significantly lower plasma leptin levels than amyloid negative participants (p < .01). CSF Aβ concentration was significantly associated with lower plasma leptin β = -4.3 (1.5), p = .005 unadjusted; and β = -3.4 (1.6), p = .03 after adjustment for age, female gender, BMI, and APOE ε4. Patients with major neurocognitive disorder due to AD had a difference of leptin of -7.3 ng/mL 95% confidence interval (CI; -11.8; -2.8), p = .0002, compared to individuals with other causes of cognitive impairment. Leptin was not associated with the slope of cognitive decline.

Conclusion: Plasma leptin levels were associated with CSF Aβ and with the diagnosis of AD confirmed by CSF biomarkers, suggesting a molecular interplay between leptin metabolism and brain amyloid deposition.

Keywords: Alzheimer’s disease; Biomarkers; Leptin; Metabolic dysfunction.