Telomeres are associated with markers and regions sensitive to aging and not Alzheimer’s disease in cognitively unimpaired older adults

Abstract

AbstractBackgroundTelomeres (protective chromosomal ends) gradually shorten over the lifespan and have been associated with the development of age‐related diseases such as Alzheimer’s disease (AD). Most studies use median telomere length as a biomarker of cellular aging, but their dysfunction is rather reflected by the load of short telomere. No study to date has assessed the links between the percentage of short telomeres (ST) and blood, neuroimaging markers of aging, neurodegeneration, amyloid and tau pathologies in healthy elderly.MethodBaseline data from 125 cognitively unimpaired older adults (65 to 83 years old; mean ± SD: 68.9 ± 2.8) from the Age‐Well trial (NCT02977819), who completed multimodal neuroimaging and blood sampling, were analyzed. Neuroimaging data included structural T1‐weighted MRI, T2‐weighted high‐resolution scan of the hippocampus, DKI, FDG‐PET and AV45‐PET (perfusion and amyloid load). ST, as well as neurodegeneration, amyloid, and tau biomarkers (NFL, GFAP, Aβ42/40 ratio and pTau181) were measured in blood samples. Multiple linear regressions between ST and each marker were conducted corrected for age, sex, education and body mass index. Additional adjustments for APOE and amyloid status were made. Statistical significance was set to p<0.05, except for voxelwise analyses (puncorrected<0.005, kuncorrected = 500 voxels).ResultST was associated with lower white matter integrity (measured by kurtosis fractional anisotropy (kFA)) in prefrontal and temporal regions (Fig.1), and with the hippocampal subiculum volume, but not with total gray matter volume, mean kurtosis, glucose metabolism, brain perfusion or amyloid load; nor with blood markers of neurodegeneration, amyloid, or tau. Additional adjustments for APOE/amyloid status gave similar results.ConclusionTelomere dysfunctions were associated with lower white matter integrity in regions vulnerable to aging, but not to AD, nor with neurodegeneration, amyloid or tau biomarkers, and neither with AD risk factors (APOE or amyloid status). When we focused on the hippocampus, a specific link was found with the subiculum volume, an hippocampal subfield known to be the most sensitive to aging, which is not the case in AD. These results give further evidence for the tight connection between cellular and cerebral aging, but not with AD in cognitively unimpaired older adults.