Diagnosis of Alzheimer's disease: defining genetic profiles (genotype vs phenotype)

The early identification of Alzheimer's disease (AD) requires a multifactorial diagnostic approach. Components of a comprehensive assessment include a clinical examination, neuropsychological and psychometric evaluations, biochemical tests, cardiovascular and radiological examinations, neuroimaging, brain bioelectrical activity mapping, an evaluation of brain hemodynamics, and assessment of biological markers. Genetic testing should be incorporated into the diagnostic protocol only for research purposes and risk evaluation. The genetic characterization of familial AD genotypes (FAD-21, FAD-14, FAD-1, FAD-19, APP-21m) can help define the phenotypic profiles of AD clinical subtypes. The correlation of genotypic and phenotypic profiles might have a predictive value in terms of AD diagnosis and therapeutic responses to particular drugs. However, available genetic markers (APP-21m, APO-E) are not yet conclusive for diagnostic purposes. In contrast, AD-related Apo-E genotypes appear to correlate with defined AD phenotypes. The presence of an Apo-E4 allele seems to represent an important risk factor for dementia.