Relationship between Adiponectin Gene Polymorphisms and Late-Onset Alzheimer’s Disease

Abstract

In recent years, researchers have found that adiponectin (ANP) plays an important role in the pathogenesis of Alzheimer's disease (AD), and low serum concentrations of ANP are associated with AD. Higher plasma ANP level have a protective effect against the development of cognitive decline, suggesting that ANP may affect AD onset. Meanwhile, accumulating evidence supports the crucial role of ANP in the pathogenesis of AD. To study the relationship between ANP gene polymorphisms (rs266729, -11377C>G and rs1501299, G276T) and late-onset AD (LOAD), we carried out a case-control study that included 201 LOAD patients and 257 healthy control subjects. Statistically significant differences were detected in the genotype and allelotype frequency distributions of rs266729 and rs1501299 between the LOAD group and the control group, with a noticeable increase in the G and T allelotype frequency distributions in the LOAD group (P < 0.05). Logistic regression analysis using recessive model and additive model revealed that the rs266729 GG and rs1501299 TT genotypes are associated with a greater risk of LOAD. Haplotype analysis identified four haplotypes: CG, CT, GG, and GT. The frequencies of the CT and GG haplotypes were not significantly different (P > 0.05) between the LOAD group and control group, whereas the CG and GT haplotypes were significantly different (P < 0.05), suggesting a negative correlation between the CG haplotype and LOAD onset (OR = 0.74, 95% CI = 0.57–0.96, P = 0.022), and a positive correlation between the GT haplotype and LOAD onset (OR = 2.29, 95% CI = 1.42–3.68, P = 0.005). Therefore, we speculated that the rs266729 and rs1501299 of ANP gene polymorphisms and the GT and CG haplotypes were associated with LOAD.

Importance of adiponectin activity in the pathogenesis of Alzheimer's disease

“…Within this framework, the mechanistic actions of APN in AD could be considered. In support of this idea, it is noteworthy that polymorphisms of the APN gene have recently been linked to sporadic AD 65, 66…”

Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice

“…Meanwhile, another clinical study demonstrated that decreased serum APN level is associated with mild cognitive impairments and AD [34]. A recent publication reported that polymorphisms in the APN gene locus were associated with higher risk of AD [32]. Although it is believed that APN crosses the BBB from the systemic circulation to the CNS, the changes of circulatory APN level may not reflect the changes of APN level in the CNS.…”

“…Our previous findings demonstrated APN to be protective against Aβ neurotoxicity [31]. Although a recent publication showed an association between APN gene polymorphism and late onset AD [32], there are contradictory clinical reports on the difference of plasma APN level between non-demented control and AD or mild cognitive impairment patients [33–35]. The role of APN in AD remains uncertain.…”

Potential Neuroprotective Effects of Adiponectin in Alzheimer’s Disease

“…In contrast to previous findings, another report showed no significant difference of adiponectin levels between a non-demented group and patients with dementia [80]. Furthermore, Yu et al found correlations between adiponectin gene polymorphism and late onset AD [81]. Two studies reported on low adiponectin levels in T2DM patients who had reduced gray matter volume, hippocampal volume and glucose metabolism, to be consistent with Alzheimer’s disease pathophysiologies [79,82].…”