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- Driscoll, Ira Frahmand, et al.
(författare)
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KLOTHO KL-VS heterozygosity is associated with diminished age-related neuroinflammation, neurodegeneration, and synaptic dysfunction in older cognitively unimpaired adults
- 2024
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Ingår i: ALZHEIMERS & DEMENTIA. - 1552-5260 .- 1552-5279.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION We examined whether the aging suppressor KLOTHO gene's functionally advantageous KL-VS variant (KL-VS heterozygosity [KL-VSHET]) confers resilience against deleterious effects of aging indexed by cerebrospinal fluid (CSF) biomarkers of neuroinflammation (interleukin-6 [IL-6], S100 calcium-binding protein B [S100B], triggering receptor expressed on myeloid cells [sTREM2], chitinase-3-like protein 1 [YKL-40], glial fibrillary acidic protein [GFAP]), neurodegeneration (total alpha-synuclein [alpha-Syn], neurofilament light chain protein), and synaptic dysfunction (neurogranin [Ng]). METHODS This Alzheimer disease risk-enriched cohort consisted of 454 cognitively unimpaired adults (Mage = 61.5 +/- 7.75). Covariate-adjusted multivariate regression examined relationships between age (mean-split[age >= 62]) and CSF biomarkers (Roche/NeuroToolKit), and whether they differed between KL-VSHET (N = 122) and non-carriers (KL-VSNC; N = 332). RESULTS Older age was associated with a poorer biomarker profile across all analytes (Ps <= 0.03). In age-stratified analyses, KL-VSNC exhibited this same pattern (Ps <= 0.05) which was not significant for IL-6, S100B, Ng, and alpha-Syn (Ps >= 0.13) in KL-VSHET. Although age-related differences in GFAP, sTREM2, and YKL-40 were evident for both groups (Ps <= 0.01), the effect magnitude was markedly stronger for KL-VSNC. DISCUSSION Higher levels of neuroinflammation, neurodegeneration, and synaptic dysfunction in older adults were attenuated in KL-VSHET.
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