Telomere Shortening in the Alzheimer’s Disease Neuroimaging Initiative Cohort

Nudelman, Kelly; Lin, J-L.; Lane, Kristin A.; K, Nho; S, Kim; Km, Faber; Risacher, Shannon L.; Foroud, Tatiana; Gao, Sujun; Jw, Davis; Weiner, M W; Aj, Saykin

doi:10.3233/jad-190010

Cited by 15 publications

(10 citation statements)

References 54 publications

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“…Likewise, another 2-year follow-up study showed reduced telomere length significantly correlated with dementia in stroke patients (32). Longitudinal investigations did not support the association between shorter telomeres and AD (15, 33). However, the recent meta-analyses with large sample size provided evidence for shorter telomere length and increased risk of AD (11, 12), and most studies have found shorter telomere length in the leukocytes of AD patients (34).…”

Section: Discussionmentioning

confidence: 87%

Exploring the Causal Pathway From Telomere Length to Alzheimer’s Disease: An Update Mendelian Randomization Study

Gao

Chen²,

Wang

et al. 2019

Front. Psychiatry

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Increasing evidence shows that telomere length shortening is associated with the risk for Alzheimer’s disease (AD), pointing to a potential modifiable target for prevention. However, the causality of this association is still not clear. To investigate the causal relationship between telomere length and AD, we use two-sample Mendelian randomization (MR) to assess potential causal inference. We used summary-level data for telomere length (9,190 participants) and AD (71,880 cases and 383,378 controls). We performed two-sample MR analysis with single nucleotide polymorphisms previously identified to be associated with telomere length. The MR analyses were conducted using the inverse-variance-weighted method and complemented with the maximum likelihood, weighted median, weighted mode approaches. MR evidence suggested that shorter telomere length was causally associated with a higher risk for AD (inverse-variance weighted estimate of odds ratio (OR): 1.03 per SD decrease of telomere length, P=1.21×10−2). The maximum likelihood, weighted median, weighted mode yielded a similar pattern of effects. The results were similar in sensitivity analyses. Using genetic instruments identified from large-scale genome-wide association study, robust evidence supports a causal role of telomere length shortening with increased risk of AD.

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Section: Discussionmentioning

confidence: 87%

Exploring the Causal Pathway From Telomere Length to Alzheimer’s Disease: An Update Mendelian Randomization Study

Gao

Chen²,

Wang

et al. 2019

Front. Psychiatry

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“…A recent longitudinal study on Alzheimer’s disease Neuroimaging Initiative Cohort focused on the TL dynamics concerning late-onset AD risk and progression. Telomere attrition rate did not differ significantly between MCI and AD group, but the later did have significantly shorter TL (Nudelman et al, 2019 ). On the other hand, longer TL at baseline was associated with rapid progression in cerebrospinal fluid biomarkers positive patients from the same cohort (Mahoney et al, 2019 ).…”

Section: Telomere Length In Brainmentioning

confidence: 99%

Telomere Attrition in Neurodegenerative Disorders

Levstek

Kozjek

Dolžan

et al. 2020

Front. Cell. Neurosci.

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Telomere attrition is increased in various disorders and is therefore a potential biomarker for diagnosis and/or prognosis of these disorders. The contribution of telomere attrition in the pathogenesis of neurodegenerative disorders is yet to be fully elucidated. We are reviewing the current knowledge regarding the telomere biology in two common neurodegenerative disorders, Alzheimer’s disease (AD), and Parkinson’s disease (PD). Furthermore, we are discussing future prospective of telomere research in these disorders. The majority of studies reported consistent evidence of the accelerated telomere attrition in AD patients, possibly in association with elevated oxidative stress levels. On the other hand in PD, various studies reported contradictory evidence regarding telomere attrition. Consequently, due to the low specificity and sensitivity, the clinical benefit of telomere length as a biomarker of neurodegenerative disease development and progression is not yet recognized. Nevertheless, longitudinal studies in large carefully selected cohorts might provide further elucidation of the complex involvement of the telomeres in the pathogenesis of neurodegenerative diseases. Telomere length maintenance is a complex process characterized by environmental, genetic, and epigenetic determinants. Thus, in addition to the selection of the study cohort, also the selection of analytical methods and types of biological samples for evaluation of the telomere attrition is of utmost importance.

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“…For more details on telomere length acquisition and quality control, see the ADNI telomere methods document on LONI (http://adni. loni.usc.edu/) and Nudelman et al [23].…”

Section: Measurement Of Telomere Lengthmentioning

confidence: 99%

Telomere length associations with cognition depend on Alzheimer's disease biomarkers

Mahoney

Dumitrescu

Seto

et al. 2019

A&D Transl Res & Clin Interv

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Introduction While telomere shortening, a marker of cellular aging, may impact the progression of age‐related neurodegenerative diseases, its association with cognition is unclear, particularly in the context of Alzheimer's disease (AD) pathology. Methods Telomere, cognitive, and CSF data from 482 participants in the AD Neuroimaging Initiative (148 cognitively normal, 283 mild cognitive impairment, 51 AD) was leveraged to assess telomere length associations with cognition (measured by memory and executive function) and interactions with CSF amyloid‐β, tau, and APOE‐ε4. Secondary analyses assessed brain volume and thickness outcomes. Results Longer telomeres at baseline were associated with faster executive function decline. Amyloid‐β and tau interacted with telomere length on cognition, with longer telomeres related to faster decline among biomarker‐positive individuals. Discussion Telomere associations with cognition shift with AD progression, with longer telomeres related to worse outcomes as pathology increases, highlighting the need for further investigation of telomere length along the AD neuropathological cascade.

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Telomere Shortening in the Alzheimer’s Disease Neuroimaging Initiative Cohort

Cited by 15 publications

References 54 publications

Exploring the Causal Pathway From Telomere Length to Alzheimer’s Disease: An Update Mendelian Randomization Study

Exploring the Causal Pathway From Telomere Length to Alzheimer’s Disease: An Update Mendelian Randomization Study

Telomere Attrition in Neurodegenerative Disorders

Telomere length associations with cognition depend on Alzheimer's disease biomarkers

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