Effects of folic acid supplementation in Alzheimer diseases‐associated mitochondrial pathology and genomic expression profiles in the 3xTg‐AD mice model

Abstract

Aims of the study were to evaluate effects of folic acid supplementation in Alzheimer diseases‐associated mitochondrial pathology and genomic expression profiles using the 3xTg‐AD mice model. Non‐transgene mice C57BL/6 mice (non‐Tg control) and 3xTg‐AD mice at 11 months were fed with the diet in the absence and presence of folic acid supplementation (FS: in drinking water and by folate gavage) for 4 months. The data revealed that FS for 4 months significantly ameliorate AD‐induced pTau expression, apoptotic signaling, mitochondrial abnormalities in fission and fusion (Mfn1 and Drp1 protein) and mitochondrial pathology in neuron myelination of AD mice. Brain folate was significantly and inversely correlated with Aβ40 deposition. Hepatic folate levels were significantly correlated with improved slope of cognition learning. Microarray analysis revealed that genetic expression profiles of AD mice hippocampus in complement and coagulation cascades, neuroactive ligand‐receptor interaction, long‐term depression, focal adhesion and Wnt signaling pathways were significantly modulated by FS, which may play the important role of AD‐associated mitochondrial pathology and neuron demyelination.