Telomere Length and the Risk of Alzheimer’s Disease: The Rotterdam Study

Abstract

There is a wide interest in biomarkers that capture the burden of detrimental factors as these accumulate with the passage of time, i.e., increasing age. Telomere length has received considerable attention as such a marker, because it is easily quantified and it may aid in disentangling the etiology of dementia or serve as predictive marker. We determined the association of telomere length with risk of Alzheimer's disease and all-cause dementia in a population-based setting. Within the Rotterdam Study, we performed quantitative PCR to measure mean leukocyte telomere length in blood. We determined the association of telomere length with risk of Alzheimer's disease until 2016, using Cox regression models. Of 1,961 participants (mean age 71.4 ± 9.3 years, 57.1% women) with a median follow-up of 8.3 years, 237 individuals were diagnosed with Alzheimer's disease. We found a U-shaped association between telomere length and risk of Alzheimer's disease: compared to the middle tertile the adjusted hazard ratio was 1.59 (95% confidence interval (CI), 1.13-2.23) for the lowest tertile and 1.47 (1.03-2.10) for the highest tertile. Results were similarly U-shaped but slightly attenuated for all-cause dementia. In conclusion, shorter and longer telomere length are both associated with an increased risk of Alzheimer's disease in the general population.

Telomere Length as a Marker of Biological Age: State-of-the-Art, Open Issues, and Future Perspectives

“…One potential explanation for this could be the enhanced level of oxidative stress in those patients (Levstek et al, 2020 ). In a more recent study, however, a U-shaped association between the TL and the risk for Alzheimer's disease was demonstrated, with both shorter and longer telomeres associated with an increased risk of this disease in the general population (Fani et al, 2020 ). Given the uncertainty of findings, the contribution of telomere attrition in the pathogenesis of neurodegenerative disorders is yet to be fully elucidated (Levstek et al, 2020 ).…”

Relationship between telomere shortening and age in Korean individuals with mild cognitive impairment and Alzheimer’s disease compared to that in healthy controls

“…However, there was a more significant telomere shortening every year among individuals with AD than in healthy individuals and those with MCI. Although shorter TLs are associated with AD [ 20 ], several studies have reported that TL is not always shorter in patients with AD than in healthy individuals [ 13 – 15 ]. Thus, TL might not be the major determinant of AD because then one might expect that individuals would develop AD as soon as telomeres shorten to a certain size [ 14 ].…”

“…Thus, TL might not be the major determinant of AD because then one might expect that individuals would develop AD as soon as telomeres shorten to a certain size [ 14 ]. In addition, a recent study found that both shorter and longer TLs were associated with an increased risk of AD [ 15 ]. Our findings demonstrated more rapid telomere shortening per year in individuals with AD than in healthy individuals and those with MCI.…”

“…Oxidative stress, inflammation, immune reactions, stress, and microglial cell degeneration in AD have been suggested as risk factors for telomere shortening [ 13 ]. In contrast, some studies have reported that TL is not always shorter in patients with AD than in individuals without AD [ 13 – 15 ]. Both short and long TLs have been associated with an increased risk of dementia [ 15 – 17 ].…”

“…In contrast, some studies have reported that TL is not always shorter in patients with AD than in individuals without AD [ 13 – 15 ]. Both short and long TLs have been associated with an increased risk of dementia [ 15 – 17 ]. These inconsistent results make it more difficult to understand the underlying relationship between TL and AD.…”