Interaction Between KLOTHO-VS Heterozygosity and APOE e4 Allele Predicts Rate of Cognitive Decline in Late-Onset Alzheimer’s Disease

Details

• Personal Author:
  Chen XR ; Sadowski MJ ; Shao Y
• Corporate Authors:
  Alzheimer's Disease Neuroimaging Initiative
• Description:
  KLOTHO-VS heterozygosity (KL-VShet+) promotes longevity and protects against cognitive decline in aging. To determine whether KL-VShet+ mitigates Alzheimer's disease (AD) progression, we used longitudinal linear-mixed models to compare the rate of change in multiple cognitive measures in AD patients stratified by APOE e4 carrier status. We aggregated data on 665 participants (208 KL-VShet-/e4-, 307 KL-VShet-/e4+, 66 KL-VShet+/e4-, and 84 KL-VShet+/e4+) from two prospective cohorts, the National Alzheimer's Coordinating Center and the Alzheimer's Disease Neuroimaging Initiative. All participants were initially diagnosed with mild cognitive impairment, later developed AD dementia during the study, and had at least three subsequent visits. KL-VShet+ conferred slower cognitive decline in e4 non-carriers (+0.287 MMSE points/year, p = 0.001; -0.104 CDR-SB points/year, p = 0.026; -0.042 ADCOMS points/year, p < 0.001) but not in e4 carriers who generally had faster rates of decline than non-carriers. Stratified analyses showed that the protective effect of KL-VShet+ was particularly prominent in male participants, those who were older than the median baseline age of 76 years, or those who had an education level of at least 16 years. For the first time, our study provides evidence that KL-VShet+ status has a protective effect on AD progression and interacts with the e4 allele. [Description provided by NIOSH]
• Subjects:
  Age Factors Aging Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Age Factors APOE Author Keywords: Alzheimer's Disease Cognitive Decline Cognitive Function KLOTHO Models Neurological Diseases Neurological Disorders
• ISSN:
  2073-4425
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  14
• Issue:
  4
• NIOSHTIC Number:
  nn:20067457
• Citation:
  Genes 2023 Apr; 14(14):917
• Contact Point Address:
  Martin J. Sadowski, Department of Biochemistry and Molecular Pharmacology, NYU Grossman School of Medicine, New York, NY 10016
• Email:
  sadowm01@med.nyu.edu
• Federal Fiscal Year:
  2023
• Performing Organization:
  New York University School of Medicine
• Peer Reviewed:
  True
• Start Date:
  20220701
• Source Full Name:
  Genes
• End Date:
  20260630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:545080f232f3b980df88a30788d5cdec9528eced1ea6e36473a1714972bb797fd839f38a26f331a10a354709b90b2a9ab1ac55da793a84f51e0deeec249d0ef2
• Download URL:
  https://stacks.cdc.gov/view/cdc/231466/cdc_231466_DS1.pdf
• File Type:
  [PDF - 1.21 MB ]