Shorter Telomere Length in Carriers of APOE-ε4 and High Plasma Concentration of Glucose, Glyoxal and Other Advanced Glycation End Products (AGEs)

Abstract

Apolipoprotein-ε4 (APOE-ε4)—common variant is a major genetic risk factor for cognitive decline and Alzheimer's disease (AD). An accelerated rate of biological aging could contribute to this increased risk. Glycation of serum proteins due to excessive glucose and reactive oxygen species leads to the formation of advanced glycation end products (AGEs)—a risk factor for diabetes and AD, and decline in motor functioning in elderly adults. Aim of present study was to investigate impact of APOE-ε4 allele containing genotype and accumulation of AGEs in plasma on telomere length (TL). Results showed that TL is significantly shorter in APOE-ε4 carriers compared with non-APOE-ε4 carriers (p = .0003). Higher plasma glucose level was associated with shorter TL irrespective of APOE-ε4 allele containing genotype (r = −.26; p = .0004). With regard to AGEs, higher plasma glyoxal and fluorescent AGEs concentrations were inversely related to TL (r = −.16; p = .03; r = −.28; p = .0001), however, plasma Nε-(carboxymethyl)lysine levels didn't correlate with TL (r = −.04; p = .57). Results support the hypotheses that APOE-ε4 carriers have shorter telomeres than noncarriers and telomere erosion is increased with higher concentration of glucose, fluorescent AGEs, and glyoxal.

Effects of apolipoprotein E polymorphism on cerebral oxygen saturation, cerebral perfusion, and early prognosis after traumatic brain injury

“…26 Moreover, studies on the cerebral cortex have shown that decreased cerebral perfusion might cause a decrease in the amount of oxygen available to brain tissue. 27,28 Therefore, impaired cerebral perfusion and cerebral oxygen metabolism may subsequently lead to poor neurological function and prognosis in patients with TBI, which is consistent with the results of the present study. In the TBI group, the mean GOS of APOE e4 carriers was significantly higher than that of APOE e4 noncarriers, suggesting that APOE e4 carriers were more likely to have worse outcomes than APOE e4 non-carriers after TBI, which is also consistent with our previous studies.…”

“… 26 Moreover, studies on the cerebral cortex have shown that decreased cerebral perfusion might cause a decrease in the amount of oxygen available to brain tissue. 27 , 28 Therefore, impaired cerebral perfusion and cerebral oxygen metabolism may subsequently lead to poor neurological function and prognosis in patients with TBI, which is consistent with the results of the present study.…”

“…Previous studies have shown that maintaining the stability of cerebral blood perfusion and cerebral oxygen metabolism after TBI is crucial for the recovery of brain function, 6,25 and weakened cerebral blood perfusion and destruction of cerebral oxygen metabolism may lead to a poor prognosis in patients with TBI 26 . Moreover, studies on the cerebral cortex have shown that decreased cerebral perfusion might cause a decrease in the amount of oxygen available to brain tissue 27,28 . Therefore, impaired cerebral perfusion and cerebral oxygen metabolism may subsequently lead to poor neurological function and prognosis in patients with TBI, which is consistent with the results of the present study.…”

Genes and Longevity of Lifespan

“…Based on several studies, a relationship between cognitive decline and e4 genotype [245], high mortality rate due to pneumonia and severe dementia have been reported in old men with e4 genotype [246]. The e4 type have been reported to have short telomeres that have a role in life expectancy [247]. In Japanese and Italian populations, e2 allele is found to favor and e4 allele decrease the chances of exceptional longevity of lifespan [248].…”

Telomere Attrition in Induced Pluripotent Stem Cell-Derived Neurons From ALS/FTD-Related C9ORF72 Repeat Expansion Carriers

“…Shortened telomere length has also been reported in AD patients as compared with age-matched controls ( Scarabino et al, 2017 ). Dhillon et al showed that ApoE4 homozygous AD patients have shorter telomeres compared to controls ( Dhillon et al, 2020 ). Telomere analysis of patients with Huntington’s disease and FTD showed telomere attrition ( Kota et al, 2015 ).…”