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KLOTHO KL-VS heterozygosity is associated with diminished age-related neuroinflammation, neurodegeneration, and synaptic dysfunction in older cognitively unimpaired adults. | LitMetric

AI Article Synopsis

  • The study investigates the impact of the KL-VS variant of the aging suppressor KLOTHO gene on age-related biomarkers related to neuroinflammation, neurodegeneration, and synaptic dysfunction in cognitively healthy adults.
  • Findings indicate that older adults show worse profiles in cerebrospinal fluid biomarkers, with KL-VS carriers experiencing lesser severity in certain neurobiological effects of aging.
  • Overall, the research suggests that the KL-VS variant may provide some protective effects against aging-related increases in neuroinflammation and other biomarkers, particularly in older adults.

Article Abstract

Introduction: We examined whether the aging suppressor KLOTHO gene's functionally advantageous KL-VS variant (KL-VS heterozygosity [KL-VS]) 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 α-synuclein [α-Syn], neurofilament light chain protein), and synaptic dysfunction (neurogranin [Ng]).

Methods: This Alzheimer disease risk-enriched cohort consisted of 454 cognitively unimpaired adults (M= 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-VS (N = 122) and non-carriers (KL-VS; N = 332).

Results: Older age was associated with a poorer biomarker profile across all analytes (Ps ≤ 0.03). In age-stratified analyses, KL-VS exhibited this same pattern (Ps ≤ 0.05) which was not significant for IL-6, S100B, Ng, and α-Syn (Ps ≥ 0.13) in KL-VS. 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-VS.

Discussion: Higher levels of neuroinflammation, neurodegeneration, and synaptic dysfunction in older adults were attenuated in KL-VS.

Highlights: Older age was associated with poorer profiles across all cerebrospinal fluid biomarkers of neuroinflammation, neurodegeneration, and synaptic dysfunction. KLOTHO KL-VS non-carriers exhibit this same pattern, which is does not significantly differ between younger and older KL-VS heterozygotes for interleukin-6, S100 calcium-binding protein B, neurogranin, and total α-synuclein. Although age-related differences in glial fibrillary acidic protein, triggering receptor expressed on myeloid cells, and chitinase-3-like protein 1 are evident for both KL-VS groups, the magnitude of the effect is markedly stronger for KL-VS non-carriers. Higher levels of neuroinflammation, neurodegeneration, and synaptic dysfunction in older adults are attenuated in KL-VS heterozygotes.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350058PMC
http://dx.doi.org/10.1002/alz.13912DOI Listing

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