Understanding the Connection Between Alzheimer Disease Plasma Biomarkers and Gait Dysfunction: Arjun Masurkar, MD, PhD; Waijha Ahmed, MD

WATCH TIME: 4 minutes

"We found that gait mean velocity was actually declining if there was an elevated level of total tau or neurofilament light, showing clear dysfunction at a preclinical level."

In recent years, there has been greater emphasis on identifying underlying cognitive, physical, and mental changes that may allude to a later-life diagnosis of neurodegenerative disorders like Alzheimer disease (AD). The discovery of biomarkers like amyloid-ß, tau proteins, and neurodegeneration markers have also enabled to development of targeted therapies and more effective clinical trials, leading to the accelerated pursuit of disease-modifying therapies. As more biomarkers are introduced, there remains a lack of data understanding the correlation between plasma biomarkers and quantitative gait variables.

At the 2024 Alzheimer’s Association International Conference (AAIC), held July 28-August 1, in Philadelphia, Pennsylvania, researchers from NYU Langone presented a new analysis linking AD plasma biomarkers with quantitative gait measures in a cognitively normal population. In the study, 129 cognitively normal patients (age 56-93; 30% Black/African American; 10% Hispanic/Latino) underwent quantitative gait analysis via the GAITRite walkway. Means and intraindividual variability (expressed as standard deviation across the laps) of gait variables were assessed over the 8 passes of the walk.

All told, results revealed a statistically significant negative association between mean velocity and neurofilament light (NfL) and total tau, after adjusting for age, sex, and apolipoprotein (APOE) genotype. More specifically, a 1 pg/ml increase in NfL was associated with a 0.33 unit decrease in mean velocity (P = .028) and a 1 pg/ml increase in total tau was associated with a 3.53 decrease in mean velocity (P = .013).

Following the meeting, study authors Arjun Masurkar, MD, PhD, and Waijha Ahmed, MD, sat down to discuss the reasons behind the study, as well as some of the notable findings. Masurkar, an associate professor in the department of neurology at the NYU Grossman School of Medicine, provided context on the prior work examining the connection between gait variables and AD biomarkers, and how this research focuses on the preclinical stages of the disease. Ahmed, an associate research scientist at NYU Langone, gave insight on the notable data observed, including the connection between gait and phosphorylated tau, as well as other markers of neurodegeneration.

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REFERENCE
1. Ahmed W, Boutajangout A, Shao Y, et al. A cross-sectional analysis of Alzheimer’s disease plasma biomarkers and gait variables in cognitively normal older adults. Presented at: Alzheimer’s Association International Conference; July 28-August 1; Philadelphia, PA. ABSTRACT 91941