THE PATHOLOGICAL PATHWAY FOR THE PERSISTENCE OF AD SYMPTOMS AFTER THE REMOVAL OF AMYLOID PLAQUES

Amyloid plaque has been an indicative hallmark for Alzheimer’s diseases (AD), however the removal of which has shown to be inefficient in altering the progression of disease; thus, the study will focus on the mechanism behind the persistence of AD. The study examines the causal relationships among Aβ, neurofibrillary tangles (NFTs), cholinergic depletion, and excitotoxicity. Using secondary data from pre-existing studies, it is evidenced that Aβ causes cholinergic depletion, NFTs, and excitotoxicity through interacting with ChaT & nAChRs, IP3-K & GSK-3β, and NR1 subunit on NMDAR respectively; NFTs causes cholinergic depletion and excitotoxicity through mitochondrial dysfunction, and interaction with vGLUT respectively; while excitotoxicity causes NFTs through interaction with cdk5 and PP2A. It is concluded that the persistence of AD after Aβ removal is due to a positive feedback loop mechanism between NFTs and excitotoxicity, which causes the persistence of NFTs, cholinergic depletion, and excitotoxicity. However, the principle causative agent of AD’s progression remains undecidable.