Evidence map›Paper›PMID 39030746›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024

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

Ira Frahmand Driscoll, Sarah Lose, Yue Ma, Barbara B Bendlin, Catherine Gallagher, Sterling C Johnson, Sanjay Asthana, Bruce Hermann, Mark A Sager, Kaj Blennow and 6 more

Abstract read
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In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Ira Frahmand DriscollWisconsin Alzheimer's Disease Research Center and Department of Geriatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Sarah LoseWisconsin Alzheimer's Disease Research Center and Department of Geriatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Yue MaWisconsin Alzheimer's Disease Research Center and Department of Geriatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Barbara B BendlinWisconsin Alzheimer's Disease Research Center and Department of Geriatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Catherine GallagherGeriatric Research Education and Clinical Center, William S. Middleton VA Hospital, Madison, Wisconsin, USA.
Sterling C JohnsonWisconsin Alzheimer's Disease Research Center and Department of Geriatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Sanjay AsthanaWisconsin Alzheimer's Disease Research Center and Department of Geriatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Bruce HermannWisconsin Alzheimer's Disease Research Center and Department of Geriatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Mark A SagerWisconsin Alzheimer's Disease Research Center and Department of Geriatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Henrik ZetterbergWisconsin Alzheimer's Disease Research Center and Department of Geriatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Cynthia CarlssonWisconsin Alzheimer's Disease Research Center and Department of Geriatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Gwendlyn KollmorgenRoche Diagnostics GmbH, Penzberg, Germany.
Clara Quijano-RubioRoche Diagnostics International Ltd, Rotkreuz, Switzerland.
Dena DubalDepartment of Neurology and Weill Institute for Neurosciences, University of California San Francisco, San Francisco, California, USA.
Ozioma C OkonkwoWisconsin Alzheimer's Disease Research Center and Department of Geriatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.

Funding

University of Wisconsin Institute for Clinical and Translational ResearchUL1TR002373 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI ELIZABETH S BURNSIDE, Allan R. Brasier · 2017 to 2026
$75.9M
Wisconsin Registry for Alzheimer's Prevention: Sex Differences in DNA MethylationR01AG027161 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Nathaniel Ark Chin, Sterling C Johnson · 2007 to 2026
$35.6M
Wisconsin Alzheimer's Disease Research CenterP30AG062715 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Barbara Brigitta Bendlin · 2019 to 2026
$34.5M
INSTITUTIONAL CTSA (UW-MADISON): CLINICAL TRIALSUL1RR025011 · NCRR · UNIVERSITY OF WISCONSIN-MADISON · PI DREZNER, MARC KENNETH · 2007 to 2011
$29.5M
White matter degeneration: biomarkers in preclinical Alzheimer's DiseaseR01AG037639 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI BENDLIN, BARBARA BRIGITTA · 2012 to 2023
$5.3M
Longitudinal Investigation of Cardiorespiratory Fitness and AD Biomarkers in an At-Risk CohortR01AG062167 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI OKONKWO, OZIOMA C · 2019 to 2023
$4.5M
KLOTHO and Resilience to Synaptic Dysfunction in Preclinical ADR01AG077507 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI Ira Frahmand, Ozioma C Okonkwo · 2023 to 2026
$3.1M
Klotho and Neurodegenerative DiseaseR01NS092918 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DUBAL, DENA BOU · 2016 to 2020
$1.7M
Clinical and Translational Science Award UL1RR025011NCATS NIH HHS UL1 TR002373NCRR NIH HHS UL1 RR025011NIA NIH HHS P30 AG062715NIA NIH HHS R01 AG027161NIA NIH HHS R01 AG037639NIA NIH HHS R01 AG062167NIA NIH HHS R01 AG077507NINDS NIH HHS R01 NS092918
6 · The paper itself

Abstract

introductionWe examined whether the aging suppressor KLOTHO gene's functionally advantageous KL-VS variant (KL-VS heterozygosity [KL-VS

methodsThis Alzheimer disease risk-enriched cohort consisted of 454 cognitively unimpaired adults (M

resultsOlder age was associated with a poorer biomarker profile across all analytes (Ps ≤ 0.03). In age-stratified analyses, 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.

Indexed as

AgingBiomarkersChitinase-3-Like Protein 1HeterozygoteKlotho ProteinsAgedalpha-SynucleinAlzheimer DiseaseCohort StudiesFemaleGlial Fibrillary Acidic ProteinGlucuronidaseHumansInterleukin-6MaleMembrane Glycoproteinsalpha-SynucleinBiomarkersCHI3L1 protein, humanChitinase-3-Like Protein 1GFAP protein, humanGlial Fibrillary Acidic ProteinGlucuronidaseIL6 protein, humanInterleukin-6Klotho ProteinsMembrane GlycoproteinsNeurograninReceptors, ImmunologicS100B protein, humanS100 Calcium Binding Protein beta SubunitTREM2 protein, humanAlzheimer's diseasechitinase‐3‐like protein 1glial fibrillary acidic proteininterleukin 6neurograninprotective factorsresilienceriskS100 calcium‐binding protein Btriggering receptor expressed on myeloid cellsα‐synuclein

Identifiers

PMID39030746
PMCPMC11350058

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.