Dataset Information
AD-associated CSF biomolecular changes are attenuated in KL-VS heterozygotes.
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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.
SUBMITTER: Driscoll I
PROVIDER: S-EPMC9728548 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
AD-associated CSF biomolecular changes are attenuated in KL-VS heterozygotes.
Alzheimer's & dementia (Amsterdam, Netherlands) 20221207 1
<h4>Introduction</h4>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 <i>KLOTHO</i> gene attenuates age-related cognitive decline and deleterious biomolecular changes.<h4>Methods</h4>Trajectories of change in memory and executive function (<i>N</i> = 360; 2-12 visits) and cerebrospinal fluid (CSF) Alzheim ...[more]