ACE Inhibitors Improve Skeletal Muscle by Preserving Neuromuscular Junctions in Patients with Alzheimer’s Disease

Article type: Research Article

Authors: Qaisar, Rizwan^{a; b; *} | Karim, Asima^a | Iqbal, M. Shahid^c | Alkahtani, Shaea A.^d | Ahmad, Firdos^{a; b; e} | Kamli, Hossam^f

Affiliations: [a] Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates | [b] Cardiovascular Research Group, Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates | [c] Department of Neurology and Stroke Medicine, Rehman Medical Institute, Peshawar, Pakistan | [d] Exercise Physiology Department, College of Sport Sciences and Physical Activity, King Saud University, Riyadh, Saudi Arabia | [e] Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, Abu Dhabi, United Arab Emirates | [f] Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia

Correspondence: [*] Correspondence to: Rizwan Qaisar, MBBS, PhD, Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, UAE. Tel.: +971 6 505 7254; Fax: +9716 5585 879; E-mail: [email protected]; ORCID: 0000-0001-8485-7172.

Abstract: Background:Hypertension and skeletal muscle decline are common findings in patients with Alzheimer’s disease (AD). Angiotensin-converting enzyme (ACE) inhibitors preserve skeletal muscle and physical capacity; however, the driving mechanisms are poorly understood. Objective:We investigated the effects of ACE inhibitors on the neuromuscular junction (NMJ) with relevance to skeletal muscle and physical capacity in AD patients and age-matched controls. Methods:We evaluated controls (n = 59) and three groups of AD patients, including normotensive (n = 51) and patients with hypertension taking ACE inhibitors (n = 53) or other anti-hypertensive medications (n = 49) at baseline and one year later. We measure plasma c-terminal agrin fragment-22 (CAF22) as a marker of NMJ degradation, handgrip strength (HGS), and Short Physical Performance Battery (SPPB) as markers of physical capacity. Results:At baseline AD patients demonstrated lower HGS and SPPB scores and higher CAF22 levels than controls, irrespective of the hypertension status (all p < 0.05). The use of ACE inhibitors was associated with higher HGS and relative maintenance of SPPB scores, gait speed, and plasma CAF22 levels. Conversely, other anti-hypertensive medications were associated with an unaltered HGS, reduced SPPB scores and elevated plasma CAF22 levels (both p < 0.05). We also found dynamic associations of CAF22 with HGS, gait speed, and SPPB in AD patients taking ACE inhibitors (all p < 0.05). These changes were associated with reduced oxidative stress in AD patients taking ACE inhibitors (p < 0.05). Conclusion:Altogether, ACE inhibitors are associated with higher HGS, preserved physical capacity, and the prevention of NMJ degradation in hypertensive AD patients.

Keywords: ACE inhibitors, Alzheimer’s disease, CAF22, handgrip strength, hypertension, short physical performance battery

DOI: 10.3233/JAD-230201

Journal: Journal of Alzheimer's Disease, vol. 94, no. 2, pp. 641-650, 2023