The Protective A673T Mutation of Amyloid Precursor Protein (APP) in Alzheimer's Disease

Alzheimer's disease is a progressive neurodegenerative disorder characterized by extracellular amyloid beta peptides and neurofibrillary tangles consisted of intracellular hyperphosphorylated Tau in the hippocampus and cerebral cortex. Most of the mutations in key genes that code for amyloid precursor protein can lead to significant accumulation of these peptides in the brain and cause Alzheimer's disease. Moreover, some point mutations in amyloid precursor protein can cause familial Alzheimer's disease, such as Swedish mutation (KM670/671NL) and A673V mutation. However, recent studies have found that the A673T mutation in amyloid precursor protein gene can protect against Alzheimer's disease, even if it is located next to the Swedish mutation (KM670/671NL) and at the same site as A673V mutation, which are pathogenic. It makes us curious about the protective A673T mutation. Here, we summarize the most recent insights of A673T mutation, focus on their roles in protective mechanisms against Alzheimer's disease, and discuss their involvement in future treatment.