ABSTRACT
Alzheimer’s disease (AD) was thought to be an intractable disorder. Yet, genetic analyses have successfully uncovered three genes, the amyloid precursor protein (APP) gene, presenilin-1 (PS-1) and the presenilin-2 (PS-2) gene which can cause early-onset Alzheimer’s disease. Functional analysis of these genes and gene mutations has highlighted the importance of the amyloid cascade hypothesis to our understanding of the disease process. Moreover, the correlation of mutations in the AD genes with specific clinical outcomes and variant neuropathology has allowed us to detect the existence of modifying factors which alter the course of the disease. More recently, the tau gene has been identified as the causative agent for another form of dementia, fronto-temporal dementia. The challenge now is to determine the enigmatic relationship between tau and the AD genes and to determine whether there is a common neurodegenerative mechanism.
