Telomere Attrition in Neurodegenerative Disorders
Levstek T, Kozjek E, Dolžan V, Trebušak Podkrajšek K. Telomere Attrition in Neurodegenerative Disorders. Front Cell Neurosci. 2020 Jul 15;14:219. doi: 10.3389/fncel.2020.00219. PMID: 32760251; PMCID: PMC7373805.
Telomere attrition is found in a number of disorders and studies have tried to understand the relationship between TL length and these disorders. This paper reviews the literature concerning TL, AD, and PD. Telomere length is maintained by telomerase and, while its activity in the brain decreases after birth, there is high activity in neuronal stem cells and neuronal progenitor cells. There are only inconsistent results between cognitive performance and TL.
Results in AD studies have been contradictory. Telomere shortening and reduced telomerase activity was found in rat microglial cells, but in aged telomerase knockout mice had decreased progression of amyloid plaque pathology. The authors think small study cohorts may be responsible for the inconsistencies since a meta-analysis showed more consistent evidence for shorter telomeres in AD.
They concluded that telomere length is a questionable biomarker for clinical use because it has low specificity and sensitivity. It could still be important because it is unclear whether telomere length is a cause or consequence of age-related disorders, but should be understood in the context of other markers.
It was interesing because I expected telomeres to be reliable biomarkers since they are a major part of cellular senescence. However, with better methods and the longitudinal studies that the authors recommend, there may be important relationships to be discovered that could contribute to the explanation of AD pathogenesis and the role of senescence.