1. 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 ε4 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 β-amyloid protein (Aβ), 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 ε4 allele in those head-injured patients displaying Aβ pathology, thus providing the first evidence for a link between a genetic susceptibility (apoE ε4) and an environmental trigger (head injury) in the development of Alzheimer-type pathology.