Detection of early Alzheimer's disease ‐like molecular alterations in a mouse model expressing human ApoE4

We show that when compared to ApoE3-expressing mice, young ApoE4-expressing mice fed a high-fat diet were more prone to metabolic disturbances like those seen in insulin resistance. We also revealed that young ApoE4-expressing mice fed a high-fat diet show the differential expression of multiple genes, leading to alterations in downstream pathways related to neuron maintenance, insulin signaling, amyloid processing and clearance, and synaptic plasticity. These findings could aid in the identification of more tractable therapeutic targets for treating ApoE4-associated Alzheimer's disease. AbstractThe E4 allele of apolipoprotein E (ApoE4) is a key genetic risk factor for late-onset Alzheimer's disease (AD), increasing the risk of developing the disease by up to three-fold. However, the mechanisms by which ApoE4 contributes to AD pathogenesis are poorly understood. Here, we utilize a mouse model expressing either human ApoE3 or human ApoE4 to examine the effects of the E4 allele on a wide range of genetic and molecular pathways that are altered in early AD pathology. We demonstrate that ApoE4-expressing mice begin to show early differential expression of multiple genes, leading to alterations in downstream pathways related to neural cell maintenance, insulin signaling, amyloid processing and clearance, and synaptic plasticity. These alterations may result in the earlier accumulation of pathological proteins such as β-amyloid that may build up within cells, leading to the accele...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research