Association of critically short telomeres with brain and blood markers of ageing and Alzheimer’s disease in older adults
Year: 2024
Type: article
Abstract: BACKGROUND: Accumulation of critically short telomeres (CST) is implicated in decreased tissular regenerative capacity and increased susceptibility to degenerative diseases such as Alzheimer's disease (AD). Telomere shortening has also been associated with age-related brain changes. However, it remains unclear whether CST accumulation is directly associated with AD markers or instead amplifies age-related effects, potentially increasing susceptibility of developing AD in cognitively healthy older adults. METHODS: This cross-sectional study used baseline data of 129 community-dwelling cognitively healthy older adults from the Age-Well trial (NCT02977819), aged 65 years and older enrolled between 2016 and 2018, in France. Using linear regressions, we analyzed the relationship between an innovative marker of telomere shortening, the percentage of CST (%CST), structural, functional and molecular neuroimaging outcomes, and multiple blood-based biomarkers related to AD pathophysiology. The effect of apolipoprotein E ε4 genotype (APOE4) was assessed on these relationships using interaction analysis. RESULTS: A higher %CST was associated with lower global kurtosis fractional anisotropy (β = -.230; P = .010), particularly in frontal and temporal regions. A higher %CST was also related to higher plasma levels of Neurofilament light chain (β = .195; P = .020) and a lower subiculum volume (β = -.206; P = .020), although these associations did not meet the threshold for multiple comparisons. %CST was not associated with AD-related neuroimaging markers, including the AD-sensitive gray matter pattern (β = -.060; P = .441), glucose metabolism pattern (β = -.099; P = .372), brain perfusion pattern (β = -.106; P = .694) or hippocampus volume (β = -.106; P = .194). In APOE4 carriers, higher %CST was associated with lower subiculum (β = -.423; P = 0.003), DG (β = -.410; P = 0.018) and CA1 volumes (β = -.373; P = 0.024), even though associations with DG and CA1 volumes did not survive multiple comparison. CONCLUSIONS: Although an increase in %CST does not appear to be directly linked to the pathophysiology of AD in cognitively healthy older adults, it could heighten the susceptibility of APOE4 carriers to develop AD plausibly due to greater vulnerability to age-related effects. However, longitudinal studies would be necessary to determine whether %CST influences the development and progression of AD later in life.
Source: Alzheimer s Research & Therapy
Authors: Asrar Lehodey, Perla Kaliman, Cassandre Palix, Robin de Florès, Edelweiss Touron, Anne-Laure Turpin, Séverine Fauvel, Florence Mézenge, Brigitte Landeau, Anne Chocat, Agathe Vrillon, Claire Paquet, Denis Vivien, Vincent de La Sayette, Gaël Chételat, Géraldine Poisnel, Claire André, Eider M. Arenaza-Urquijo, Pierre Champetier, Fabienne Colette, Robin De Flores, Marion Delarue, Francesca Felisatti, Egantine Ferrand Devouge, Antoine Garnier-Crussard, Julie Gonneaud, Marc Heidmann, Frank Jessen, Olga Klimecki, Elizabeth Kuhn, Gwendoline Le Du, Valérie Lefranc, Antoine Lutz, Natalie Marchant, Florence Mezenge, Inès Moulinet, Valentin Ourry, Léo Paly, Stefano Poletti, Anne Quillard, Géraldine Rauchs, Stéphane Rehel, Eric Salmon, Siya Sherif, Matthieu Vanhoutte, Patrik Vuilleumier, Caitliin Ware, Miranka Wirth
Institutions: Inserm, Normandie Université, Cyceron, Physiopathologie et imagerie des troubles neurologiques, Université de Caen Normandie, Universitat Oberta de Catalunya, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Hôpital Fernand-Widal, Hôpital Lariboisière, Optimisation Thérapeutique en Neuropsychopharmacologie, Centre Hospitalier Universitaire de Caen Normandie
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,990
OpenAlex ID: W4405651584