Hormonal
Obesity-associated leptin resistance, driven by impaired BBB transport and intracellular signaling inhibition (PTP1B/SOCS3), contributes to cognitive decline and Alzheimer's disease pathology by disrupting synaptic plasticity and memory formation.
For those with obesity or aging-related cognitive concerns, addressing metabolic health is critical for brain health. The paper suggests that the failure of leptin signaling (leptin resistance) is a key driver of cognitive decline, not just high leptin levels. Interventions that improve metabolic health may help restore leptin sensitivity and protect against cognitive decline.
Decreased leptin signaling in the CNS may be related to defective leptin transport across BBB, LepR downregulation and/or deficient leptin signaling downstream LepRs... impaired brain leptin signaling may play a role in AD pathophysiology
Why this rating
The paper is a review citing multiple human and animal studies, but notes controversial findings regarding leptin levels in AD patients.
Source
The Role of Leptin and Adiponectin in Obesity-Associated Cognitive Decline and Alzheimer’s Disease
Letícia Forny‐Germano et al. · Frontiers in Neuroscience · 2019
DOI 10.3389/fnins.2018.01027
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