MUTANT-GENES IN FAMILIAL ALZHEIMERS-DISEASE AND TRANSGENIC MODELS

The most common cause of dementia occurring in mid-to late-life is Alz heimer's disease (AD). Some cases of AD, particularly those of early o nset, are familial and inherited as autosomal dominant disorders linke d to the presence of mutant genes that encode the amyloid precursor pr otein (APP) or (he presenilins (PS1 or PS2). These mutant gene product s cause dysfunction/death of vulnerable populations of nerve cells imp ortant in memory, higher cognitive processes, and behavior. AD affects 7-10% of individuals >65 years of age and perhaps 40% of individuals >80 years of age. For the late-onset cases, the principal risk factors are age and apolipoprotein (apoE) allele type, with apoE4 allele bein g a susceptibility factor. In this review, we briefly discuss the clin ical syndrome of AD and the neurobiology/neuropathology of the disease and then focus attention on mutant genes linked to autosomal dominant familial AD (FAD), the biology of the proteins encoded by these genes , and the recent exciting progress in investigations of genetically en gineered animal models that express these mutant genes and develop som e features of AD.