Genetics of dementias, Part 4: A spectrum of mutations responsible for the familial autosomal dominant form of Alzheimer's disease

Fifty years ago it was demonstrated that some patients with Alzheimer's disease (AD) had an autosomal dominant Mendelian pattern of disease inheritance. Familial and early-onset cases ( familial Alzheimer's disease, FAD) are rather rare and account for only a few percent of the total population of patients. Mutations of the genes for amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are responsible for development of the disease in 50 percent of patients with FAD. The identification of mutations in FAD genes leads to a better understand of the molecular basis of the cellular pathways leading to neurodegeneration. With the detection of genetic defects responsible for FAD, there is considerable interest in the application of this genetic information in medical practice through genetic testing and counseling for families with Alzheimer's disease.