The impact of genetic and environmental factors on the pathobiology of Alzheimer's disease: a multifactorial disorder?

Summary

Alzheimer's disease is the most common form of dementia, although its diagnosis can only be confirmed after autopsy. While 10% of cases show a family history of the disease, the remainder are sporadic. Disease-causing mutations in three genes (amyloid precursor protein and two presenilin genes) have been discovered which account for nearly all of the familial cases of Alzheimer's disease. The sporadic forms of the disease are associated with a number of genetic risk factors (apolipoprotein E, x₁antichymotrypsin, very low density lipoprotein receptor and mitochondrial DNA mutations) but none of these are either sufficient on their own or necessary for the disease. This leaves open the possibility that one or more extrinsic environmental factors may affect the progression of Alzheimer's disease. Although the evidence for specific extrinsic factors is lacking, the role of putative agents (aluminium, antioxidants, head trauma) and how they might interact with intrinsic genetic factors is discussed. Alzheimer's disease, therefore, demonstrates genetic heterogeneity and, in addition, may be considered as a multifactorial disorder.