Question

Variants of ApoE (epsilon4 allele) are one of the best-known genetic risk factors for Alzheimer’s. Propose a mechanism by which this variant may contribute to the disease process.

Answer 1

ApoE is an apoliprotein that helps in the transport of lipids in the body. In brain ApoE is produced by Astrocytes. Among the three variations of ApoE, epsilon 4 ApoE is the cause of early onset of Alzheimer's disease. This is a neurodegenerative disease in which neurons are damged resulting in dementia.

The ApoE produced by Astrocytes transport lipid by attaching to the neural receptors. The ApoE also regulates a protein called Amyloid beta peptide which is the main component in senile plaques(dark patches in grey matter of brain) and plays a role in toxicating neurons. The variation in ApoE (epsilon 4 ApoE) cannot regulate Amyloid beta peptide and their imbalance leads to the formation of aggregates in the brain. These Amyloid beta peptide aggregates associate with neuro fibrillar tangles of tau protein and directly blocks the nerve signal and damages the neurons. This leads to the Alzheimer's disease.