Immunotherapy in Alzheimer’s Disease: Current Status and Future Directions

Issue title: Therapeutic Trials in Alzheimer’s Disease: Where Are We Now?

Guest editors: Paula I. Moreira, Jesus Avila, Daniela Galimberti, Miguel A. Pappolla, Germán Plascencia-Villa, Aaron A. Sorensen, Xiongwei Zhu and George Perry

Article type: Review Article

Authors: Vashisth, Kshitij^{a; 1} | Sharma, Shivani^b | Ghosh, Shampa^{a; c; 1} | Babu, M. Arockia^d | Ghosh, Soumya^a | Iqbal, Danish^e | Kamal, Mehnaz^f | Almutary, Abdulmajeed G.^g | Jha, Saurabh Kumar^h | Ojha, Shreeshⁱ | Bhaskar, Rakesh^{j; k; *} | Jha, Niraj Kumar^{l; *} | Sinha, Jitendra Kumar^{a; *}

Affiliations: [a] GloNeuro, Noida, India | [b] Department of Pharmaceutics, R.K.S.D. College of Pharmacy, Kaithal, Haryana, India | [c] ICMR – National Institute of Nutrition, Tarnaka, Hyderabad, India | [d] Institute of Pharmaceutical Research, GLA University, Mathura, India | [e] Department of Health Information Management, College of Applied Medical Sciences, Buraydah Private Colleges, Buraydah, Saudi Arabia | [f] Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia | [g] Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, Abu Dhabi, United Arab Emirates | [h] Department of Zoology, Kalindi College, University of Delhi, New Delhi, India | [i] Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates | [j] School of Chemical Engineering, Yeungnam University, Gyeonsang, Korea | [k] Research Institute of Cell Culture, Yeungnam University, Gyeongsan, Korea | [l] Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India

Correspondence: [*] Correspondence to: Dr. Niraj Kumar Jha, Assistant Professor, Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India. E-mail: [email protected]; and Dr. Jitendra Kumar Sinha, Chief Scientific Officer, GloNeuro Academy, Sector 107, Vishwakarma Road, Noida 201301, India. E-mails: [email protected], [email protected] and Dr. Rakesh Bhaskar, Assistant Professor, School of Chemical Engineering, Yeungnam University, Gyeonsang 38541 Republic of Korea. E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Alzheimer’s disease (AD) is a progressive neurological disorder characterized by memory loss, cognitive decline, and behavioral changes. Immunotherapy aims to harness the immune system to target the underlying pathology of AD and has shown promise as a disease-modifying treatment for AD. By focusing on the underlying disease pathogenesis and encouraging the removal of abnormal protein aggregates in the brain, immunotherapy shows promise as a potential treatment for AD. The development of immunotherapy for AD began with early attempts to use antibodies to target beta-amyloid. The amyloid hypothesis which suggests that the accumulation of beta-amyloid in the brain triggers the pathological cascade that leads to AD has been a driving force behind the development of immunotherapy for AD. However, recent clinical trials of monoclonal antibodies targeting amyloid-β have shown mixed results, highlighting the need for further research into alternative immunotherapy approaches. Additionally, the safety and efficacy of immunotherapy for AD remain an area of active investigation. Some immunotherapeutic approaches have shown promise, while others have been associated with significant side effects, including inflammation of the brain. Sleep has a significant impact on various physiological processes, including the immune system, and has been linked to the pathogenesis of AD. Thus, improving sleep quality and duration may benefit the immune system and potentially enhance the effectiveness of immunotherapeutic approaches for AD. In this review, we discussed the promises of immunotherapy as a disease-modifying treatment for AD as well as possible methods to improve the efficacy and safety of immunotherapy to achieve better therapeutic outcomes.

Keywords: Alzheimer’s disease, amyloid-β, dementia, immunotherapy, personalized medicine, sleep-immune interactions

DOI: 10.3233/JAD-230603

Journal: Journal of Alzheimer's Disease, vol. 101, no. s1, pp. S23-S39, 2024