Altered β-APP Metabolism After Head Injury and its Relationship to the Aetiology of Alzheimer’s Disease

There is increasing evidence of a link between head injury and the subsequent onset of Alzheimer’s disease. Deposits of amyloid β-protein (Aβ) are found not only in cases of dementia pugilistica but in some 30% of patients dying after a single episode of severe head injury. Detailed clinicopathological studies have shown that Aβ deposition is most likely, but not exclusively, to occur, the older the patient at the time of injury, and if the injury is the result of a fall. Distribution studies have shown that the Aβ is widely deposited in the neocortex and there is no apparent association with any of the multiple primary or secondary pathologies of traumatic brain injury. There is an increased expression of β-APP particularly in the pre-α cells of the entorhinal cortex and in areas of axonal damage. Recent molecular genetic studies have shown that there is a strong association between deposits of As and the apolipoprotein E genotype of the individual.