Concurrent anti-amyloid therapy and exercise for the treatment of alzheimer's disease

The National Institute on Aging, a component of the Department of Health and Human Services National Institutes of Health, awarded $301,575 to the Palo Alto Veterans Institute for Research on September 1, 2026, under the Aging Research program (CFDA 93.866) to conduct a two-year project grant testing the combined effectiveness of the anti-amyloid medication lecanemab and exercise training for Alzheimer's disease treatment.

The recipient will use the 3XTG-AD mouse line to evaluate whether concurrent lecanemab therapy and exercise reduce Alzheimer's disease pathology and facilitate neural communication, with secondary aims to measure cognitive outcomes. The study addresses multiple dimensions of neurodegeneration—amyloid plaque accumulation, inflammation, and deficits in neural communication—hypothesizing that exercise enhances treatment efficacy by increasing brain-derived neurotrophic factor and regulating microglia activity. The research is performed at the Palo Alto, California facility with a period of performance from September 1, 2026, through August 31, 2028. The Aging Research program supports biomedical and behavioral research directed toward understanding the aging process and diseases affecting older populations, with particular emphasis on Alzheimer's disease and related dementias.

Abstract

Alzheimer's disease (ad) affects nearly 7 million individuals in the united states, with limited effective treatment options. Anti-amyloid therapies have shown promise but often fail to improve cognition despite addressing pathology. Ad involves inflammation and deficits in neural communication alongside plaque accumulation, necessitating treatments that extend beyond plaque removal for maximum efficacy. Exercise has shown promise in enhancing neural communication and reducing inflammation through many mechanisms, including increasing brain-derived neural trophic factor (bdnf) and regulating microglia. Combining exercise with the anti-amyloid medication lecanemab could improve the quality of life for patients with ad by addressing multiple dimensions of ad pathology. The study thus aims to test the effectiveness of combining lecanemab with exercise training for ad using the 3XTG-ad mouse line. We hypothesize that this treatment regimen will reduce ad pathology and facilitate neural communication (aim 1); and decrease cognitive loss (aim 2). This innovative project addresses the multidimensional components of neurodegeneration and has the potential for expansion to more complex research projects. Results will uniquely shed light on the direct brain biochemical response to lecanemab and exercise in a controlled experimental setting, facilitating translation into clinical care recommendations.