Candidate Gene Association Studies in Sporadic Alzheimer’s Disease

Abstract

The genetics of Alzheimer’s disease (AD) is complex. Three genes (amyloid precursor protein, presenilin 1 and presenilin 2) have been described in the relatively rare, early-onset, autosomal dominant familial form of AD. In the common, non-familial (sporadic) late-onset AD, the major known genetic risk factor is the Ε4 allele of the apolipoprotein E (APOE) gene. However, at least half of the people who develop AD do not carry this allele, and not all people who do carry this allele develop AD even if they live to an old age. Therefore, approximately 30 other candidate genes involving a protein in a critical pathway in the pathogenesis of disease (principally interaction with amyloid-β, oxidative stress and inflammation/apoptosis) have been considered as risk factors for sporadic AD. Then these genes have been sequenced in search of genetic variability or polymorphisms, and each putative polymorphism has been reported to alter the risk of AD either directly or by an interaction with the APOE Ε4 allele. However, positive-association studies with these candidate genes have not been consistently confirmed.

Identification of Differentially Expressed Genes in Scrapie-Infected Mouse Brains by Using Global Gene Expression Technology

“…Additionally, cathepsins B and L demonstrated increased expression in RML-and ME7-infected mouse brains, respectively. An imbalance of cathepsins, a family of lysosomal proteases, has been associated with neurodegenerative diseases, including Alzheimer's disease and prion disease (2,11,12,13,56). Our observations of up-regulated cathepsin expression again confirmed these previous findings.…”

Genetic Analysis of Alzheimer’s Disease in the Uppsala Longitudinal Study of Adult Men

“…Specifically for dementia, 80 genes involved in 3 major pathways known to affect brain function were selected: A ␤ /lipid metabolism, oxidative stress and inflammation/apoptosis [2] . In addition, genes positioned within previously identified AD linkage peaks were also selected.…”

“…The association of apolipoprotein E (APOE) to Alzheimer's disease (AD) has been convincingly and repeatedly demonstrated in numerous studies [1] . Additional susceptibility genes for AD have been more elusive and studies aimed at identifying such genes have, prior to whole-genome approaches, mainly been focused on genes with a demonstrated or implied function related to de-mentia development or genes chromosomally positioned within linkage peaks correlated to AD [2,3] . However, genes implicated in other complex conditions could also potentially be relevant to dementia.…”

Effect of Manasamitra Vatakam Against Aluminium Induced Learning and Memory Impairment of Apoptosis in Rat’s Hippocampus and Cortex

“…The previous studies observed that MMV act as a potential effect against Al induced free radical generation of oxidative stress protein (HSP70) involved neuronal damage of nerve cells evidenced by histological studies [10]. Altmann et al [11] confirmed that Al causes considerable damage of cerebral function include learning memory impairment in rats was linked to develop Alzheimer's disease (AD) [12,13]. Exacerbation of normal aging related changes and neuronal apoptosis has played key factor for impairment learning memory and neurodegenerative disorders [14][15][16].…”