The Role of Amyloid Beta and Tau in the Pathology of Alzheimer’s Disease

Neurotoxic amyloid beta plaques and neurofibrillary tau tangles are often known as the two main proteins attributed to the pathological hallmarks of Alzheimer’s disease (AD). This disease is a prevalent type of dementia that is often known to be associated with aging, memory loss, and no cure. This review examines the amyloidogenic processing of amyloid-β precursor protein (APP) into the amyloid β-42 peptide, the encoding of microtubule-associated protein tau (MAPT) through RNA splicing and phosphorylation, and the genetic factors (isoforms, alleles, chromosomal locations, and regulatory enzymes) that contribute to mutation risk in Alzheimer’s disease. Recent studies suggest that tau may play a more critical role, as the distribution and density of tau aggregates had a stronger correlation with the clinical stage of AD. This suggestion challenges the ongoing debate on the amyloid cascade hypothesis: amyloid-beta oligomers, rather than plaque, play a more critical role in Alzheimer’s disease pathology by triggering downstream events that lead to tau tangles. The amyloid beta peptide activates glycogen synthase kinase 3 (GSK3), which phosphorylates tau protein. This sequence leads to the formation of insoluble toxic aggregates that protein phosphatases cannot effectively dephosphorylate in some patients.