Amyloid protein in Alzheimer's disease

Abstract

Progressive deposition of amyloid fibrils in senile plaques and in blood vessels is a pathological hallmark of Alzheimer's disease. The AD amyloid protein, called beta amyloid protein, or A4 protein, is derived from a much larger precursor protein, the gene for which has now been cloned, sequenced, and localized to chromosome 21. This chromosomal location is of great interest because it has long been known that all Down's patients over the age of 40 develop the classical neuropathological lesions of AD. An anonymous DNA marker, which segregates with cases of dominantly inherited AD, has also been found to be located on chromosome 21. It is now known, however, that this marker and the gene encoding the beta amyloid precursor protein are not tightly linked. The beta amyloid precursor protein gene appears to code for a normal cellular product whose function is not yet known. The gene is expressed not only in brain but also in many non-neural tissues. It is highly conserved in evolution. Two closely related alternative transcripts have recently been identified; these contain an insert showing homology to certain members of the Kunitz family of proteinase inhibitors. All evidence accumulated thus far suggests that the beta amyloid precursor protein gene is not abnormal in AD; therefore, recent research has focused on transcriptional, translational, or posttranslational events that may be implicated in the progressive deposition of beta amyloid protein in AD.