Relationship of Alzheimer’s Disease and Related Dementias Plasma Biomarkers With Mobility in Cognitively Unimpaired Older Adults

Product:

CNS Disease Panel 120

Topic:

Neurology

Disease Area:

Alzheimer's Disease

Sample Type:

Plasma

Topic/Product:

CNS Disease Panel 120

Disease Area:

Alzheimer's Disease

Sample Type:

Plasma

Abstract

Background

Temporal relationships between physical and cognitive decline with aging are poorly understood, and little is known about the underlying mechanisms linking these conditions. We hypothesized that plasma biomarkers of Alzheimer’s disease and related dementias may be associated with mobility performance in older adults who are cognitively unimpaired.

Methods

We constructed separate linear mixed models to examine the cross-sectional associations of 5 plasma Alzheimer’s disease and related dementias and aging-related biomarkers with 4 measures of mobility in a cohort of 192 cognitively unimpaired older adults. We secondarily described the association of the same biomarkers with 4 cognitive domain scores.

Results

Higher phorphorylated-tau181 was associated with worse performance on the expanded short physical performance battery, slower 4 m gait speed, and shorter balance time. Higher neurofilament light was associated with worse expanded short physical performance battery, slower 4 m gait speed, and slower 400 m gait speed in adjusted models. However, there was no association of Aβ₄₂/Aβ₄₀, p-tau217, or glial fibrillary acidic protein with mobility. Only p-tau217 was associated with global and processing speed cognitive domain scores in multivariable models, but not after adjusting for multiple comparisons.

Conclusions

These data suggest that p-tau181 and neurofilament light are potential markers of mobility performance in cognitively normal older adults, even when they are not associated with cognitive performance. Future studies should examine how such markers predict change over time in mobility and cognitive function and whether they may indicate pathways that could be targeted for preventive management.

Authors & Affiliations

Atalie C. Thompson, MD, MPH,1,2,*, Xiaoyan Leng, PhD,3 Michael E. Miller, PhD,4 Thomas C. Register, PhD,5 Paul J. Laurienti, MD, PhD,6 Michelle M. Mielke, PhD,2,7, Suzanne Craft, PhD,2 and Stephen B. Kritchevsky, PhD2,

Department of Ophthalmology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Division of Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Department of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Department of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition. He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.