Alzheimer's disease is a heterogeneous disorder that may be caused by genetic or environmental factors or by a combination of both. Abnormalities in chromosomes 1, 14, and 21 have all been implicated in the pathogenesis of the early-onset form of the disease, while the epsilon 4 allele of the apolipoprotein E gene (on chromosome 19) is now recognized as a risk factor for early- and late-onset sporadic and familial Alzheimer's disease. 2. The best-established environmental trigger for the disease is a head injury, 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 is 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 providing the first evidence for a link between a genetic susceptibility (apoE epsilon 4) and an environmental trigger (head injury) in the development of Alzheimer-type pathology.
