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

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 (A beta), 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 epsilon 4. 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 A beta concentration was significantly associated with lower plasma leptin beta = -4.3 (1.5), p = .005 unadjusted; and beta = -3.4 (1.6), p = .03 after adjustment for age, female gender, BMI, and APOE epsilon 4. 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 A beta and with the diagnosis of AD confirmed by CSF biomarkers, suggesting a molecular interplay between leptin metabolism and brain amyloid deposition.

Automated summary

This study examined the associations between plasma leptin levels and cognitive impairment stages, as well as CSF biomarkers in AD. Results showed a negative correlation between plasma leptin levels and CSF β-amyloid concentration, and confirmed the diagnosis of AD through CSF biomarkers.