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REVIEW ARTICLE

Neurodegeneration in Alzheimer’s disease: A narrative review of mechanistic insights and emerging therapeutic approaches

Md. Nazmul Hossain1 ,  Rabeya Sultana Badhon1 ,  Mohammad Shahangir Biswas2,3* ,  Munna Kumar Podder1 ,  Suronjit Kumar Roy1 ,  Rubait Hasan1 ,  Md. Moyen Uddin Pk4
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1 Department of Biochemistry and Biotechnology, Khwaja Yunus Ali University, Sirajganj, Bangladesh
2 Department of Biochemistry and Biotechnology, University of Science and Technology Chittagong, Chittagong, Bangladesh
3 Department of Public Health, Daffodil International University, Dhaka, Bangladesh
4 Institute of Biological Sciences, Rajshahi University, Rajshahi, Bangladesh
Advanced Neurology, 025160040 https://doi.org/10.36922/AN025160040
Received: 20 April 2025 | Revised: 4 August 2025 | Accepted: 13 August 2025 | Published online: 29 August 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder responsible for 50–75% of dementia cases worldwide, primarily affecting individuals over 65 years of age. It is characterized by cognitive decline, memory loss, and behavioral abnormalities. Key pathological features include extracellular β-amyloid (Aβ) plaques, intracellular neurofibrillary tangles of hyperphosphorylated tau protein, mitochondrial dysfunction, and cholinergic system impairment. Despite extensive research, the precise etiology remains unclear, and current treatments only alleviate symptoms without halting disease progression. A comprehensive literature review was conducted using peer-reviewed articles from PubMed, Scopus, and Google Scholar, emphasizing recent studies on molecular mechanisms, risk factors, diagnostics, and therapies. Major pathogenic mechanisms identified include oxidative stress, tau hyperphosphorylation, Aβ aggregation, and synaptic degeneration. Non-modifiable risk factors such as aging, genetic mutations in amyloid precursor protein, phosphatidylinositol-binding clathrinid assembly protein, presenilin 1/2, and the apolipoprotein E ε4 allele play significant roles, whereas modifiable risks involve lifestyle factors and comorbidities such as diabetes. Diagnostic advancements highlight the promise of blood-based biomarkers, although current practices rely heavily on cerebrospinal fluid markers and neuroimaging. Approved pharmacological interventions, including cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists, provide limited symptomatic relief. Ongoing research into Aβ- and tau-targeted therapies has yielded mixed results. In addition, novel approaches such as tripartite motif-containing protein 2-mediated tau clearance and deep cervical lymphatic-venous anastomosis are being explored for their potential in targeting intracellular aggregates and enhancing brain waste clearance. AD emerges as a multifactorial condition driven by a complex interplay of biological, genetic, and environmental factors. Although substantial progress has been made in understanding its pathophysiology, effective disease-modifying therapies remain elusive. Continued advances in biomarker discovery and personalized therapeutic strategies offer hope for improved early detection and targeted treatment approaches.

Keywords
Alzheimer’s disease
Neurodegeneration
Amyloid-beta
Mitochondrial dysfunction
Biomarkers
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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