Use of Genetic Variation as Biomarkers for Alzheimer's Disease

Abstract

Late-onset Alzheimer's disease (LOAD) is the most common cause of late-onset dementia in western societies. Despite remarkable achievements in human genetics throughout the years, in particular technological advances in gene mapping and in statistical methods that relate genetic variants to disease, to date only a small proportion of the genetic contribution to LOAD can be explained leaving several remaining genetic risk factors to be identified. A possible explanation for the difficulty in gene identification is that LOAD is a multifactorial complex disorder with both genetic and environmental components. Multiple genes with small effects each ("quantitative trait loci" [QTLs]) are likely to contribute to the quantitative traits associated with the disease, such as memory performance, amyloid/tau pathology, or hippocampal atrophy. The motivation for identifying the genetics of LOAD is clear. Not only could it shed light on disease pathogenesis, but it may also provide potential targets for effective treatment, screening, and prevention. Here, we review the usefulness of genetic variation as diagnostic tools and biomarkers in LOAD and discuss the potentials and difficulties researchers face in designing appropriate studies for gene discovery.

Prediction of Mild Cognitive Impairment that Evolves into Alzheimer's Disease Dementia within Two Years using a Gene Expression Signature in Blood: A Pilot Study

“…This is also well in agreement with similar findings in previous AD studies [34][35][36][37][38]. The results also support the concept of AD as a multifactorial sporadic disorder [54] with multiple genes and alterations in gene expression involved [55,56]. A␤ processing appears to be a significant canonical pathway and apoptosis a significant biological function represented among the proteins encoded by the 225 assay set.…”

GSTM1 null genotype as risk factor for late-onset Alzheimer's disease in Italian patients

“…The only risk factor already confirmed for LOAD is the ε4-allele of apolipoprotein E (APOE); however, the APOE4 allele is neither a necessary nor a sufficient risk factor for AD. Thus, the presence of additional genetic risk factors is suggested [6][7][8].…”

Association between NMDA receptor subunit 2b gene polymorphism and Alzheimer’s disease in Chinese Han population in Shanghai

“…Actually, the occurrence of AD is correlated with a diversity of factors, including both genetic and environmental aspects [1] . Even the genetic aspect alone may involve more than a dozen of gene variants [29] and each of these variants contributes to the pathogenesis of AD to a gentle degree that can not be detected in a small size of subjects.…”