ADVANCES IN ALZHEIMER'S DISEASE TREATMENT
Abstract
Alzheimer's disease (AD) remains one of the greatest challenges in modern medicine, serving as the leading cause of dementia in the elderly. Despite decades of research, effective causal treatment is still not available, and current therapies mainly focus on alleviating symptoms. However, in recent years, there has been significant progress in therapies targeting pathological proteins – amyloid β (Aβ) and tau – offering hope for modifying the course of the disease. In this review, we discuss the latest achievements in AD treatment, including clinical trial results involving monoclonal antibodies (lecanemab, donanemab), the role of biomarkers in early diagnosis, and the impact of non- pharmacological interventions such as diet and physical activity. Additionally, we analyze the challenges associated with anti-amyloid therapy, including side effects and limitations of current methods. We also emphasize the importance of personalized medicine and future research directions that may lead to breakthroughs in Alzheimer's disease therapy.
Materials and methods: This review was conducted systematically to identify and analyze relevant scientific literature regarding advancements in the treatment and diagnosis of Alzheimer's disease. The PubMed database was searched. Articles were searched using the following words: "Anti-amyloid therapies"; "Alzheimer's disease"; "Lekanemab"; "Donanemab"; "Alzheimer's biomarkers"; "Cerebrospinal fluid"; "CSF"; "Tau protein"; "Non- pharmacological interventions"; "Mediterranean diet"; "Dementia prevention"; "Amyloid- related imaging abnormalities"; "Disease-modifying therapies”; „traumatic brain injury”.
References
Sevigny J, et al. The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. Nature. 2016;537(7618):50-56.
van Dyck CH, et al. Lecanemab in Early Alzheimer's Disease. N Engl J Med. 2023;388(1):9-21.
Mintun MA, et al. Donanemab in Early Alzheimer's Disease. N Engl J Med. 2021;384(18):1691-1704.
Swanson CJ, et al. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early
Alzheimer's disease with lecanemab, an anti-Aβ protofibril antibody. Alzheimers Res Ther. 2021;13(1):80.
Lowe SL, et al. Donanemab (LY3002813) dose-escalation study in Alzheimer's disease. Alzheimers Dement (N Y). 2021;7(1):e12112.
Logovinsky V, et al. Safety and tolerability of BAN2401--a clinical study in Alzheimer's disease with a protofibril selective Aβ antibody. Alzheimers Res Ther. 2016;8:14.
Budd Haeberlein S, et al. Clinical Development of Aducanumab, an Anti-Aβ Human Monoclonal Antibody Being Investigated for the Treatment of Early Alzheimer's Disease. J Prev Alzheimers Dis. 2017;4(4):255-263.
Sperling RA, et al. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer's Association Research Roundtable Workgroup. Alzheimers Dement. 2011;7(4):367-385.
Knopman DS, et al. Aducanumab: Evidence from Clinical Trial Data and Controversies. Drugs Context. 2021;10:2021-7-3.
Jack CR Jr, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535-562.
Lin GA, et al. Aducanumab for Alzheimer's Disease: Effectiveness and Value; Final Evidence Report. Institute for Clinical and Economic Review, 2021.
Salloway S, et al. Amyloid-related imaging abnormalities in 2 phase 3 studies evaluating aducanumab in patients with early Alzheimer disease. JAMA Neurol. 2022;79(1):13-21.
Schneider LS. A critical review of the amyloid hypothesis and the impact of anti-amyloid therapies on drug discovery for Alzheimer's disease. J Prev Alzheimers Dis. 2022;9(4):585-592.
Lowe SL, et al. Donanemab (LY3002813) Phase 1b Study in Alzheimer's Disease: Rapid and Sustained Reduction of Brain Amyloid Measured by Florbetapir PET. J Prev Alzheimers Dis. 2021;8(4):414-424.
Hey JA, et al. Discovery and Identification of an Endogenous Metabolite of Tramiprosate and Its Prodrug ALZ-801 that Inhibits Beta Amyloid Oligomer Formation in the Human Brain. CNS Drugs. 2018;32(9):849- 861.
Hansson O, et al. Blood-based biomarkers for Alzheimer's disease. Nat Rev Neurol. 2022;18(6):323- 336.
Cummings J, et al. Alzheimer's disease drug development pipeline: 2023. Alzheimers Dement (N Y). 2023;9(2):e12385.
Tolar M, et al. The path forward in Alzheimer's disease therapeutics: Reevaluating the amyloid cascade hypothesis. Alzheimers Dement. 2020;16(11):1553-1560.
Jack Jr CR, Bennett DA, Blennow K, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimer’s & Dementia. 2018;14(4):535-562.
Hansson O, Edelmayer RM, Boxer AL, et al. The Alzheimer’s Association appropriate use recommendations for blood biomarkers in Alzheimer’s disease. Nature Reviews Neurology. 2022;18(6):323- 336.
Palmqvist S, Janelidze S, Quiroz YT, et al. *Discriminative accuracy of plasma phospho-tau217 for Alzheimer disease vs other neurodegenerative disorders.* JAMA. 2020;324(8):772-781.
Ossenkoppele R, Rabinovici GD, Smith R, et al. Discriminative accuracy of [18F]flortaucipir positron emission tomography for Alzheimer disease vs other neurodegenerative disorders. JAMA. 2018;320(11):1151-1162.
Janelidze S, Mattsson N, Palmqvist S, et al. *Plasma P-tau181 in Alzheimer’s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia.* Nature Medicine. 2020;26(3):379-386.
Schindler SE, Bollinger JG, Ovod V, et al. *High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis.* Neurology. 2019;93(17):e1647-e1659.
Mattsson-Carlgren N, Janelidze S, Palmqvist S, et al. *Longitudinal plasma p-tau217 is increased in early stages of Alzheimer’s disease.* Brain. 2020;143(11):3234-3241.
Barthelemy NR, Li Y, Joseph-Mathurin N, et al. A soluble phosphorylated tau signature links tau, amyloid and the evolution of stages of dominantly inherited Alzheimer’s disease. Science Translational Medicine. 2020;12(524):eaaz5347.
Leuzy A, Cullen NC, Mattsson-Carlgren N, Hansson O. Current advances in plasma and cerebrospinal fluid biomarkers in Alzheimer’s disease. Current Opinion in Neurology. 2021;34(2):266-274.
Moscoso A, Grothe MJ, Ashton NJ, et al. *Time course of phosphorylated-tau181 in blood across the Alzheimer’s disease spectrum.* Brain. 2021;144(2):325-339.
Pontecorvo MJ, Devous Sr MD, Navitsky M, et al. Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition. Brain. 2017;140(3):748-763.
Zetterberg H, Bendlin BB. Biomarkers for Alzheimer’s disease—preparing for a new era of diseasemodifying therapies. Molecular Psychiatry. 2021;26(1):296-308.
Livingston G, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020;396(10248):413-446.
Norton S, et al. Potential for primary prevention of Alzheimer's disease: an analysis of population-based data. Lancet Neurol. 2014;13(8):788-794.
Cao L, et al. Mediterranean diet and risk of dementia: a systematic review and meta-analysis. Clin Nutr. 2022;41(6):1243-1254.
Hardman RJ, et al. Adherence to a Mediterranean-style diet and effects on cognition in adults: a systematic review and meta-analysis of RCTs. Nutrients. 2021;13(7):2345.
Dyall SC. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Front Aging Neurosci. 2015;7:52.
Ngandu T, et al. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015;385(9984):2255-2263.
Sanders LMJ, et al. Dose-response relationship between exercise and cognitive function in older adults with and without cognitive impairment: a systematic review and meta-analysis. PLoS One. 2019;14(1):e0210036.
Hill NT, et al. Computerized cognitive training in older adults with mild cognitive impairment or dementia: a systematic review and meta-analysis. Am J Psychiatry. 2017;174(4):329-340.
Williamson JD, et al. Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial. JAMA. 2019;321(6):553-561.
Biessels GJ, et al. Dementia and cognitive decline in type 2 diabetes and prediabetic stages: towards targeted interventions. Lancet Diabetes Endocrinol. 2014;2(3):246-255.
Osorio RS, et al. Sleep-disordered breathing advances cognitive decline in the elderly. Neurology. 2015;84(19):1964-1971.
Kivipelto M, et al. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): study design and progress. Alzheimers Dement. 2013;9(6):657-665.
Rosenberg A, et al. Multidomain interventions to prevent cognitive impairment, Alzheimer's disease, and dementia: from FINGER to World-Wide FINGERS. J Prev Alzheimers Dis. 2020;7(1):29-36.
Baumgart M, et al. Summary of the evidence on modifiable risk factors for cognitive decline and dementia: a population-based perspective. Alzheimers Dement. 2015;11(6):718-726.
Isaacson RS, et al. The clinical practice of risk reduction for Alzheimer's disease: a precision medicine approach. Alzheimers Dement. 2018;14(12):1663-1673.
van Dyck CH, et al. Lecanemab in early Alzheimer's disease. N Engl J Med. 2023;388(1):9-21.
Mintun MA, et al. Donanemab in early Alzheimer's disease. N Engl J Med. 2021;384(18):1691-1704.
Scheltens P, et al. Alzheimer's disease. Lancet. 2021;397(10284):1577-1590.
Novak P, et al. Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Neurol. 2017;16(2):123-134.
Tolar M, et al. The path forward in Alzheimer's disease therapeutics: reevaluating the amyloid cascade hypothesis. Alzheimers Dement. 2020;16(11):1553-1560.
Heneka MT, et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol. 2015;14(4):388-405.
Hansson O, et al. Blood-based biomarkers for Alzheimer's disease. Nat Rev Neurol. 2022;18(6):323-336.
Dagum P. Digital biomarkers of cognitive function. NPJ Digit Med. 2018;1:10.
Frisoni GB, et al. The probabilistic model of Alzheimer disease: the amyloid hypothesis revised. Nat Rev Neurosci. 2022;23(1):53-66.
Lin PJ, et al. Alzheimer's disease cascade hypothesis and economic value of treatment. Alzheimers Dement. 2020;16(11):1553-1560.
Karlawish J, et al. Addressing the ethical, policy, and social challenges of preclinical Alzheimer disease. Neurology. 2017;89(15):1568-1579.
Gauthier S, et al. Alzheimer's disease: the benefits of early treatment. Eur J Neurol. 2022;29(6):1754-1763.
Vogt NM, et al. Gut microbiome alterations in Alzheimer's disease. Sci Rep. 2017;7(1):13537.
Cummings J, et al. Alzheimer's disease drug development pipeline: 2023. Alzheimers Dement (N Y). 2023;9(2):e12385.
Knopman DS, et al. Alzheimer disease. Nat Rev Dis Primers. 2021;7(1):33.
Prince M, et al. World Alzheimer Report 2015: the global impact of dementia. Alzheimer's Disease International, 2015.
Views:
0
Downloads:
0
Copyright (c) 2025 Bartosz Krawiec, Maja Ćwiek, Klaudia Malec, Amin Omidi, Bartłomiej Zarębski, Jakub Sójka, Maksymilian Szombara, Michał Mokrzyński, Piotr Szyszka, Olaf Jadanowski
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
