Driscoll, Ira;
Ma, Yue;
Lose, Sarah R;
Gallagher, Catherine L;
Johnson, Sterling C;
Asthana, Sanjay;
Hermann, Bruce P;
... Okonkwo, Ozioma C; + view all
(2022)
AD-associated CSF biomolecular changes are attenuated in KL-VS heterozygotes.
Alzheimers Dementia
, 14
(1)
, Article e12383. 10.1002/dad2.12383.
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Abstract
INTRODUCTION: Dementia as an inevitable aging consequence has been challenged and underscores the need for investigations of the factors that confer resilience. We examine whether the functionally advantageous KL-VS variant of the putative aging suppressor KLOTHO gene attenuates age-related cognitive decline and deleterious biomolecular changes. METHODS: Trajectories of change in memory and executive function (N = 360; 2-12 visits) and cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers-amyloid beta (Aβ)42, total tau (t-tau), phosphorylated tau (p-tau) (N = 112; 2-4 samplings)-were compared between KL-VS non-carriers and heterozygotes in middle-aged and older adults from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center studies. RESULTS: Memory and executive function declined (p's ≤ 0.001) and CSF t-tau, p-tau, t-tau/Aβ42, and p-tau/Aβ42 levels increased (all p's ≤ 0.004) with age. The rate of p-tau accumulation was attenuated for KL-VS heterozygotes (p = 0.03). DISCUSSION: KL-VS heterozygosity may confer resilience to AD-associated biomolecular changes.
| Type: | Article |
|---|---|
| Title: | AD-associated CSF biomolecular changes are attenuated in KL-VS heterozygotes |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/dad2.12383 |
| Publisher version: | https://doi.org/10.1002/dad2.12383 |
| Language: | English |
| Additional information: | © 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
| Keywords: | Alzheimer's disease, CSF, biomarkers, executive function, memory, tau |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10162411 |
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