Telomere length, brain tau deposition and cognitive decline: Two‐year follow‐up study

Abstract

AbstractBackgroundTelomere length (TL) is known to be associated with aging and various age‐related diseases. However, previous studies on the relationship between the TL and Alzheimer’s disease (AD) yielded inconsistent results, and the association between TL and in vivo AD pathologies such as cerebral beta‐amyloid (Aβ) and tau deposition remains unclear. We investigated whether TL is related to in vivo AD pathologies and predicts future cognitive decline.MethodTotal 132 older adults recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease were included for analysis. For all participants, absolute TL values (aTL) were measured by a quantitative PCR method using DNA extracted from whole blood at baseline, as aTL can provide more direct comparison between experiments and laboratories compared to traditional TL assays. Global PiB retention measured 11C‐PiB‐PET and global tau deposition in the regions corresponding to Braak stages measured by 18F‐AV‐1451 PET were used in this study. For clinical outcome, conversion of clinical diagnosis and change of MMSE score assessed at baseline and 2‐year follow‐up was used.ResultAmong 132 older adults, 71 of them were cognitively normal and 51 of them were cognitively impaired (39 MCI and 22 AD dementia) at baseline and total 20 individuals converted to MCI or AD dementia during 2 year follow‐up period. No significant group difference in aTL was observed between diagnostic groups at baseline. However, aTL at baseline was significantly longer in converters (N=20) compared to non‐converters (N=112) even after adjusting age, sex, APOE4 positivity and baseline diagnosis. In addition, the difference of MMSE score between baseline and 2‐year follow‐up showed positive association with baseline aTL after adjusting age, sex, education, APOE4 and baseline diagnosis. With regard to in vivo AD pathologies, baseline aTL had a significant positive association with global tau deposition, but not with global Aβ deposition.ConclusionOur finding suggests that longer TL relates to greater tau deposition in brain and more rapid cognitive decline in older adults. Further studies to elucidate mechanism underlying the association of TL with tau deposition and cognitive decline will be necessary.