ABSTRACT
Alzheimer’s disease (AD) is a heterogeneous disorder in which more than 50 different genes distributed across the human genome may be involved.1,2 It’s phenotypic features and current biological markers3 are inconsistent and do not always correlate with a defined genotypic profile. This suggests that environmental factors and epigenetic phenomena may also contribute to the premature phenotypic expression of dementia, represented by its neuropathological hallmarks (amyloid deposition in senile plaques and brain vessels, neurofibrillary tangle (NFT) formation, synaptic loss, neuronal death) and clinical symptoms (memory deficit, behavioral changes, functional decline). Furthermore, 60-80% of the therapeutic failures in AD can be potentially attributed to problems associated with both pharmacogenetic and pharmacogenomic factors. In order to advance towards a mature genomic medicine of dementia, we have to incorporate functional genomics, proteomics, pharmacogenomics, high-throughput screening methods, combinatorial chemistry and bioinformatics to the AD field with the prospective view of improving diagnostics and therapeutics by using the modern tools provided by these disciplines.4 This is particularly important in
complex/polygenic multifactorial disorders in which genetic factors are modulated by both environmental and epigenetic phenomena, as might be the case in more than 90% of the central nervous system (CNS) disorders with clinical onset in adulthood and the elderly.2
