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We investigated TL in the default mode network (DMN), which underlies episodic memory deficits in AD, as well as shelterin protein and mRNA levels in the precuneus (PreC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Telomere length was evaluated in DMN hubs and visual cortex using quantitative PCR (qPCR). In the PreC, western blotting and NanoString nCounter expression analyses evaluated shelterin protein and mRNA levels, respectively, in cases with an antemortem clinical diagnosis of no cognitive impairment (NCI), MCI and AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TL was significantly reduced in the PreC in MCI and AD compared to NCI, but stable in frontal, inferior temporal, posterior cingulate and visual cortex. PreC TL correlated significantly with performance on cognitive tests. NCI cases with high vs low Braak scores displayed significantly shorter TL in posterior cingulate and frontal cortex, which correlated significantly with neuritic and diffuse amyloid\u2010\u03b2 plaque counts. Shelterin protein levels (TIN2, TRF1, TRF2 and POT1) declined in MCI and AD compared to NCI. The PreC displayed stable expression of shelterins <jats:italic>TERF1<\/jats:italic>, <jats:italic>TERF2<\/jats:italic>, <jats:italic>POT1<\/jats:italic>, <jats:italic>RAP1<\/jats:italic> and <jats:italic>TPP1<\/jats:italic>, while <jats:italic>TINF2<\/jats:italic> mRNA significantly increased in AD compared to NCI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings indicate a selective vulnerability to telomere attrition within different nodes of the DMN in prodromal AD and in aged NCI individuals with high Braak scores highlighting a putative role in the pathogenesis of AD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12672","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T02:39:32Z","timestamp":1603766372000},"page":"428-440","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Telomeric alterations in the default mode network during the 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