Role of neuronal fabp in autophagy and amyloid-β pathology in a Drosophila model of Alzheimer disease.

Abstract

FABP3 and FABP7 are members of the fatty acid-binding protein (FABP) family that transport fatty acids to intracellular organelles, which are elevated in patients with Alzheimer disease (AD). However, their role in the disease pathogenesis remain poorly understood. In a Drosophila model of AD, neuronal fabp knockdown inhibited autophagic flux and increased amyloid-beta (Aβ) aggregation, exacerbating neurodegeneration. Conversely, fabp overexpression had the opposite effect and improved memory. The modulation of Ecdysone-induced protein 75B (Eip75B) levels, the Drosophila homolog of peroxisome proliferator-activated receptor, a lipid-activated nuclear receptor that functions as a transcription factor, affected the expression of autophagy-related genes and the role of fabp in Aβ pathology. These results suggest that fabp regulates Aβ pathology through autophagy by modulating Eip75B and highlight the importance of proper fatty acid transport in neurons for autophagy regulation and Aβ pathogenesis.