Volume : 12, Issue : 11, November – 2025
Title:
A COMPREHENSIVE OVERVIEW OF ALZHEIMER’S DISEASE: PATHOPHYSIOLOGY, DIAGNOSIS, AND THERAPEUTIC ADVANCES
Authors :
Shivani L. Katpalliwar, Ankita S. Sarnaik, Swati P. Deshmukh
Abstract :
Alzheimer’s disease; amyloid-β; tau; neuroinflammationAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and functional impairment. This review synthesizes currentunderstanding of AD pathogenesis, including amyloid-β aggregation, tau phosphorylation, neuroinflammation, synaptic dysfunction, and mitochondrial oxidative stress, alongside genetic and lifestyle risk factors. We compare classifications by onset, clinical stages, and biomarker profiles, evaluate pharmacologic and herbal therapeutic approaches, and examine advances in diagnostics and disease-modifying strategies. Emphasis is placed on translational research, challenges in therapeutic development, and future directions such as targeted immunotherapies, precision medicine, and improved drug delivery systems. Recommendations for research priorities and clinical management are presented.
Keywords: biomarkers; disease-modifying therapies; cognitive decline; precision medicine.
Cite This Article:
Please cite this article in press Shivani L. Katpalliwar et al., A Comprehensive Overview Of Alzheimer’s Disease: Pathophysiology, Diagnosis, And Therapeutic Advances, Indo Am. J. P. Sci, 2025; 12(11).
REFERENCES:
1. Jack CR Jr, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535–62.
2. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging–Alzheimer’s Association workgroups. Alzheimers Dement. 2011;7(3):263–9.
3. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the NIA-AA workgroups. Alzheimers Dement. 2011;7(3):280–92.
4. Braak H, Braak E. Neuropathological staging of Alzheimer-related changes. Acta Neuropathol. 1991;82(4):239–59.
5. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science. 2002;297(5580):353–6.
6. Selkoe DJ, Hardy J. The amyloid hypothesis at 25 years. EMBO Mol Med. 2016;8(6):595–608.
7. Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, Maier M, et al. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature. 2016;537(7618):50–6.
8. van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in early Alzheimer’s disease. N Engl J Med. 2023;388(1):9–21.
9. Kivipelto M, Ngandu T, Laatikainen T, Winblad B, Soininen H, Tuomilehto J. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): Study design and primary findings. Alzheimers Dement. 2013;9(6):657–65.
10. World Health Organization. Risk reduction of cognitive decline and dementia: WHO guidelines. Geneva: WHO; 2019.
11. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late-onset families. Science. 1993;261(5123):921–3.
12. Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: A meta-analysis. JAMA. 1997;278(16):1349–56.
13. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: Clinical characterization and outcome. Arch Neurol. 1999;56(3):303–8.
14. Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol. 2004;55(3):306–19.
15. Rogers SL, Doody RS, Mohs RC, Friedhoff LT; Donepezil Study Group. Donepezil improves cognition and global function in Alzheimer disease: A 15-week, double-blind, placebo-controlled study. Arch Intern Med. 1998;158(9):1021–31.
16. Rogers SL, Doody RS, Mohs R, et al. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease. Neurology. 1998;50(1):136–45.
17. Reisberg B, Doody R, Stöffler A, Schmitt F, Ferris S, Möbius HJ. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med. 2003;348(14):1333–41.
18. Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;(1):CD005593.
19. Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, et al. Alzheimer’s disease. Lancet. 2021;397(10284):1577–90.
20. Alzheimer’s Association. 2023 Alzheimer’s Disease Facts and Figures. Alzheimers Dement. 2023;19(4) (Special Report).
21. Glenner GG, Wong CW. Alzheimer’s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun. 1984;120(3):885–90.
22. Tanzi RE. The genetics of Alzheimer disease. Cold Spring Harb Perspect Med. 2012;2(10):a006296.
23. De Strooper B, Karran E. The cellular phase of Alzheimer’s disease. Cell. 2016;164(4):603–15.
24. Goedert M, Spillantini MG. Propagation of tau aggregates and neurodegeneration. Brain. 2017;140(2):266–8.
25. Frigerio CS, Racke MK. Alzheimer’s disease mechanisms and emerging roads to therapy. Nat Rev Neurol. 2016;12(1):1–15.
26. van Bokhoven P, Cummings J, Hendrix S, et al. The Alzheimer’s disease drug development landscape. Alzheimers Res Ther. 2021;13(1):164.
27. Zhang J, Wang J, Huang Y. Recent advances in Alzheimer’s disease: Mechanisms and therapeutic strategies. Signal Transduct Target Ther. 2024;9(1