--Increasing evidence links metabolic disorders, such as obesity and type 2 diabetes, to a higher risk of AD, potentially through mechanisms involving insulin resistance, mitochondrial dysfunction, chronic inflammation, and cerebrovascular/BBB dysfunction [PMID: 30022099; PMID 32993686]. These processes may impair neuronal bioenergetics and disrupt protein-clearance pathways, contributing to the accumulation of neurotoxic proteins.

--Therapeutic strategies that enhance autophagic clearance, such as the FDA-approved tyrosine kinase inhibitor nilotinib, have therefore emerged as potential approaches to mitigate AD pathology. [PMID: 39459541]

--This study examined whether high-fat diet–induced metabolic dysfunction alters cognitive, mitochondrial, and neuropathological outcomes in 3xTg-AD mice, and whether nilotinib treatment can mitigate AD pathology and associated cognitive-behavioral deficits.

This work was supported by the National Institutes of Health [grant number R16NS134540] and Nova Southeastern University’s Barry and Judy Silverman College of Pharmacy. Corresponding Author: Benedict C. Albensi [balbensi@nova.edu]