Amyloid β‐Protein, APOE Genotype and Head Injury

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Abstract
Deposition of amyloid β-protein (Aβ) in the brain plays a key role in the pathogenesis of Alzheimer's disease. Head injury is an epidemiological risk factor for Alzheimer's disease, and deposition of Aβ occurs in approximately one third of individuals dying shortly after a severe head injury. Of the three common apolipoprotein E alleles (APOE-ε2, ε3, and ε4) APOE-ε4 allele is a strong risk factor for both sporadic and some familial cases of Alzheimer's disease and there is in vitro evidence that apolipoprotein E is directly involved in Aβ deposition. We have examined the frequency of APOE-ε4 in those individuals with Aβ deposition following head injury and found that the APOE-ε4 frequency (0.52) is higher than in most studies of sporadic Alzheimer's disease. In those head-injured individuals without amyloid deposition the APOE-ε4 frequency (0.16) is similar to that in non-Alzheimer's disease controls (p < 0.00001). Our data indicate an interaction between known environmental and genetic risk factors for Alzheimer's disease and underlines the importance of convergence of data around the common mechanism of Aβ deposition. Furthermore, it indicates a genetic susceptibility to the effects of a head injury which may be of significance both to those who have recently sustained such an injury and to those whose activities put them at risk of trauma.