Insights into the Pathophysiology of Alzheimer’s Disease and Potential Therapeutic Targets: A Current Perspective

Article type: Review Article

Authors: Rajah Kumaran, Kesevan^a | Yunusa, Suleiman^{b; d} | Perimal, Enoch^{e; f} | Wahab, Habibah^c | Müller, Christian P.^{b; g} | Hassan, Zurina^{b; g; *}

Affiliations: [a] Malaysian Institute of Pharmaceuticals and Nutraceuticals, National Institutes of Biotechnology Malaysia, Halaman Bukit Gambir, Gelugor, Pulau Pinang, Malaysia | [b] Centre for Drug Research, Universiti Sains Malaysia, Penang, Malaysia | [c] School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia | [d] Department of Pharmacology, Bauchi State University Gadau, Bauchi State, Nigeria | [e] Curtin Medical School, Curtin University, Bentley, Western Australia, Australia | [f] Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia | [g] Section of Addiction Medicine, Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany

Correspondence: [*] Correspondence to: Zurina Hassan, PhD, Centre for Drug Research, Universiti Sains Malaysia, 11800 Minden, Penang, Malaysia. Tel.: +604 6532726; Fax: +604 6568669; E-mail: [email protected].

Abstract: The aging population increases steadily because of a healthy lifestyle and medical advancements in healthcare. However, Alzheimer’s disease (AD) is becoming more common and problematic among older adults. AD-related cases show an increasing trend annually, and the younger age population may also be at risk of developing this disorder. AD constitutes a primary form of dementia, an irreversible and progressive brain disorder that steadily damages cognitive functions and the ability to perform daily tasks. Later in life, AD leads to death as a result of the degeneration of specific brain areas. Currently, the cause of AD is poorly understood, and there is no safe and effective therapeutic agent to cure or slow down its progression. The condition is entirely preventable, and no study has yet demonstrated encouraging findings in terms of treatment. Identifying this disease’s pathophysiology can help researchers develop safe and efficient therapeutic strategies to treat this ailment. This review outlines and discusses the pathophysiology that resulted in the development of AD including amyloid-β plaques, tau neurofibrillary tangles, neuroinflammation, oxidative stress, cholinergic dysfunction, glutamate excitotoxicity, and changes in neurotrophins level may sound better based on the literature search from Scopus, PubMed, ScienceDirect, and Google Scholar. Potential therapeutic strategies are discussed to provide more insights into AD mechanisms by developing some possible pharmacological agents for its treatment.

Keywords: Alzheimer’s disease, amyloid plaques, cholinergic, neurodegeneration, neuroinflammation, pharmacological agent, tau tangles

DOI: 10.3233/JAD-220666

Journal: Journal of Alzheimer's Disease, vol. 91, no. 2, pp. 507-530, 2023