What is the pathophysiology of Alzheimer's?

Answer 1

There are different types of Alzheimer disease. The early-onset AD is a rare inheritable autosomal dominant disorder that involves mutations in the presenilin genes and presents before age 40. The presenilin-1 gene (chromosome 14) and the presenilin-2 gene (chromosome 1). It is also associated with Down syndrome (trisomy 21). These patients have increased risk of developing Alzheimer's because the amyloid beta precursor protein (APP) gene is located on chromosome 21.  

The other type is late-onset AD. In this case there are mutations in apolipoprotein E (APOE) that is located on chromosome 19. There are different allele variations. The ε4 is associated with increased risk of AD and the ε2 is associated with decreased risk for the disease. 

The diagnosis is mainly clinical but after death we can see some histologic changes in the brain like senile neuritic plaques composed of AB amyloid, neurofibrillary tangles which are intracellular accumulations of a hyperphosphorylated tau protein (cytoskeletal protein0, and neuronal degeneration. This last detail results in diffuse cortical atrophy.