1. Alzheimer's disease is a heterogeneous disorder that may be caused by ge
netic or environmental factors or by a combination of both. Abnormalities i
n chromosomes 1, 14, and 21 have all been implicated in the pathogenesis of
the early-onset form of the disease, while the epsilon 3 allele of the apo
lipoprotein E gene (on chromosome 19) is nov: recognized as a risk factor f
or early- and late-onset sporadic and familial Alzheimer's disease.
2. The best-established environmental trigger for the disease is a head inj
ury, based on epidemiological and neuropathological evidence. Approximately
30% of patients who die after a single episode of severe head injury show
intracerebral deposition of beta-amyloid protein (A beta), a protein that i
s thought to be central to the pathogenesis of Alzheimer's disease.
3. Recent studies have revealed an over-representation of the apoE epsilon
4 allele in those head-injured patients displaying A beta pathology, thus p
roviding the first evidence for a link between a genetic susceptibility (ap
oE epsilon 4) and an environmental trigger (head injury) in the development
of Alzheimer-type pathology.