Genetic and Other Approaches in Combination

Introduction

The use of genetic and/or environmental risk factor information in combination with sensitive tests that monitor changes in the sensory systems and brain morphology and/or function is one approach that is being explored for direct and earlier AD diagnosis. In this section we explain how one genetic risk factor (the ApoE 4 allele) is being used in combination with other clinical information to increase the specificity of probable AD diagnosis. There now is evidence that persons with different ApoE genotypes react differently to certain Alzheimer drugs (95,317). One problem

Fig. 2. Possible involvement of the neuroendocrine and immune systems in acute phase reaction in Alzheimer disease. CRF, corticotropin-releasing factor; 5-HT, sera-tonin; ACTH, adrenocorticotropin; NK, natured killer. (After ref. 48.)

with using ApoE genotyping as a diagnostic adjunct is that the effects of the ApoE 4 allele are not the same in different ethnic groups (181). Furthermore, there now is evidence for a nonrandom association between the ApoE and ACT loci in women which may have an important implication for the higher prevalence of AD in women (175). Roses (326) has explained how more than one genetic risk factor (possibly in combination with environmental risk factors) and clinical tests might be used to classify participants in clinical trials into subgroups so that effects of drugs and treatments on persons with AD of different etiological origin can be examined. Tables 2 to 4 summarize published information about genetic and environmental risk factors for AD.

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