ArticleJournal of Alzheimer's disease : JAD2021
Age-Related Tau Burden and Cognitive Deficits Are Attenuated in KLOTHO KL-VS Heterozygotes.
Article in Journal of Alzheimer's disease : JAD, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Longevity Factor Klotho and Resistance to Cognitive Deficits in Individuals with Parkinson's Disease and in an α-Synuclein Mouse Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Klotho deficiency and cognitive impairment in dialysis patients: mechanisms, clinical evidence, and therapeutic implications.Frontiers in aging neuroscience · 2026Review
- KLOTHO-VS heterozygosity, α-klotho protein levels and cognitive performance in Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Associations of KLOTHO-VS heterozygosity and α-Klotho protein with cerebrospinal fluid Alzheimer's disease biomarkers.Journal of Alzheimer's disease : JAD · 2025Article
- Amyloid-β positivity is less prevalent in cognitively unimpairedJournal of Alzheimer's disease : JAD · 2024Article
- KLOTHO KL-VS heterozygosity is associated with diminished age-related neuroinflammation, neurodegeneration, and synaptic dysfunction in older cognitively unimpaired adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Longevity factor klotho enhances cognition in aged nonhuman primates.Nature aging · 2023Article
- Can accelerated ageing models inform us on age-related tauopathies?Aging cell · 2023Review
- Interaction betweenGenes · 2023Article
- Association of Klotho Protein Levels and KL-VS Heterozygosity With Alzheimer Disease and Amyloid and Tau Burden.JAMA network open · 2022Article
- KL1 Domain of Longevity Factor Klotho Mimics the Metabolome of Cognitive Stimulation and Enhances Cognition in Young and Aging Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- AD-associated CSF biomolecular changes are attenuated in KL-VS heterozygotes.Alzheimer's & dementia (Amsterdam, Netherlands) · 2022Article
- Exploiting the neuroprotective effects of α-klotho to tackle ageing- and neurodegeneration-related cognitive dysfunction.Neuronal signaling · 2021Review
- Urinary Incontinence and Alzheimer's Disease: Insights From Patients and Preclinical Models.Frontiers in aging neuroscience · 2021Review
- More fit KL-VS heterozygotes have more favorable AD-relevant biomarker profiles.Alzheimer's & dementia (New York, N. Y.)Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundIdentification of new genetic variants that modify Alzheimer's disease (AD) risk will elucidate novel targets for curbing the disease progression or delaying symptom onset.
objectiveTo examine whether the functionally advantageous KLOTHO gene KL-VS variant attenuates age-related alteration in cerebrospinal fluid (CSF) biomarkers or cognitive function in middle-aged and older adults enriched for AD risk.
methodsSample included non-demented adults (N = 225, mean age = 63±8, 68% women) from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center who were genotyped for KL-VS, underwent CSF sampling and had neuropsychological testing data available proximal to CSF draw. Covariate-adjusted multivariate regression examined relationships between age group (Younger versus Older; mean split at 63 years), AD biomarkers, and neuropsychological performance tapping memory and executive function, and whether these relationships differed between KL-VS non-carriers (KL-VSNC) and heterozygote (KL-VSHET).
resultsIn the pooled analyses, older age was associated with higher levels of total tau (tTau), phosphorylated tau (pTau), and their respective ratios to amyloid-β (Aβ)42 (ps ≤ 0.002), and with poorer performance on neuropsychological tests (ps ≤ 0.001). In the stratified analyses, KL-VSNC exhibited this age-related pattern of associations with CSF biomarkers (all ps ≤ 0.001), and memory and executive function (ps ≤ 0.003), which were attenuated in KL-VSHET (ps ≥ 0.14).
conclusionWorse memory and executive function, and higher tau burden with age were attenuated in carriers of a functionally advantageous KLOTHO variant. KL-VS heterozygosity seems to be protective against age-related cognitive and biomolecular alterations that confer risk for AD.
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Registered trials
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