Voluntary Wheel Running Reduces Amyloid-β₄₂ and Rescues Behavior in Aged Tg2576 Mouse Model of Alzheimer’s Disease

Article type: Research Article

Authors: Francis, Nikita^{a; b} | Robison, Lisa S.^{a; 1} | Popescu, Dominique L.^{a; b} | Michaelos, Michalis^{a; 2} | Hatfield, Joshua^b | Xu, Feng^b | Zhu, Xiaoyue^b | Davis, Judianne^b | Anderson, Maria E.^{a; 3} | Anderson, Brenda J.^a | Van Nostrand, William E.^b | Robinson, John K.^{a; c; *}

Affiliations: [a] Department of Psychology, Stony Brook University, Stony Brook, NY, USA | [b] George & Anne Ryan Institute for Neuroscience and Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, USA | [c] George & Anne Ryan Institute for Neuroscience and Department of Psychology, University of Rhode Island, Kingston, RI, USA

Correspondence: [*] Correspondence to: Dr. John K. Robinson, George & Anne Ryan Institute for Neuroscience and Department of Psychology, University of Rhode Island, 130 Flagg Road, Kingston, RI 02881, USA. E-mail: [email protected].

Note: [1] Current affiliation: Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY, USA.

Note: [2] Current affiliation: Janelia Research Campus, Ashburn, VA, USA.

Note: [3] Current affiliation: Department of Psychology, Farmingdale State College, Farmingdale, NY, USA.

Abstract: Exercise has been shown to be protective against the risk of dementias, including Alzheimer’s disease (AD). Intervention studies have demonstrated its ability to mitigate cognitive and behavioral impairments and reduce disease in both humans and animals. However, information is lacking in regard to the volume and intensity, as well as timing of exercise onset with respect to disease stage, which produces optimal benefits. Here, utilizing the Tg2576 mouse, a model of AD-like parenchymal amyloid pathology and cognitive impairment, we sought to understand the effects of different lengths of daily access to a running wheel on advanced stage disease. This study is the first to determine the benefits of long-term exercise (4 months of voluntary running) and different periods of daily access to a running wheel (0 h, 1 h, 3 h, and 12 h running wheel access) beginning in 14-month-old Tg2576 mice, an age with significant amyloid pathology. We found that exercising Tg2576 animals showed lower levels of some aspects of AD pathology and reduced behavioral dysfunction compared to sedentary Tg2576 animals. High intensity exercise, rather than high volume exercise, was generally most beneficial in reducing amyloid pathology. Our results suggest that engaging in vigorous exercise programs, even after living a sedentary life, may lead to a measurable reduction in AD pathology and preservation of some cognitive abilities.

Keywords: Amyloid, behavior, dementia, exercise, transgenic

DOI: 10.3233/JAD-190810

Journal: Journal of Alzheimer's Disease, vol. 73, no. 1, pp. 359-374, 2020