Alzheimer’s disease

AD is the most common form of elderly dementia and has no effective therapy. Clinical diagnosis is based on the evaluation of cognitive function and lab tests. Pathological diagnosis is based on post-mortem neuropathology, defined by three hallmarks: senile plaque, NFT, and neuronal cell loss. Senile plaque mainly consists of Aβ aggregates and serves as a focal point of astrocyte and microglial activation, while NFT contains hyperphosphorylated tau. Aβ is produced during the processing of APP by BACE and the γ-secretase complex that includes PS1. Both APP and PS1 are causative genes of AD, while apoE4 is a risk factor allele. The Aβ load in CNS is maintained by balancing its production and clearance, which is mediated by passive diffusion to blood stream, degradation by Aβ degrading enzymes (IDE and neprilysin), and microglial phagocytosis. Aβ production, deposition, and neurodegeneration are significantly regulated by astroglial and microglial activation via direct contact as well as secretion of a number of neurotoxicants. Specific pro-inflammatory cytokines, chemokines, and excitotoxins have been characterized as mediators of neuroinflammation and neurotoxicity. Currently their specific roles in mediating the pathogenesis in AD are being explored. Those diverse studies are generating a large number of potential therapeutic targets for treating AD. Beneficial effects have been reported for anti-inflammatory drugs, such as NSAIDs, to treat glial inflammation and disease progression.