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Symptomatic and Disease-Modifying Therapy Pipeline for Alzheimer’s Disease: Towards a Personalized Polypharmacology Patient-Centered Approach
Open accessAbstract
Since 1906, when Dr. Alois Alzheimer first described in a patient “a peculiar severe disease process of the cerebral cortex”, people suffering from this pathology have been waiting for a breakthrough therapy. Alzheimer’s disease (AD) is an irreversible, progressive neurodegenerative brain disorder and the most common form of dementia in the elderly with a long presymptomatic phase. Worldwide, approximately 50 million people are living with dementia, with AD comprising 60–70% of cases. Pathologically, AD is characterized by the deposition of amyloid β-peptide (Aβ) in the neuropil (neuritic plaques) and blood vessels (amyloid angiopathy), and by the accumulation of hyperphosphorylated tau in neurons (neurofibrillary tangles) in the brain, with associated loss of synapses and neurons, together with glial activation, and neuroinflammation, resulting in cognitive deficits and eventually dementia. The current competitive landscape in AD consists of symptomatic treatments, of which there are currently six approved medications: three AChEIs (donepezil, rivastigmine, and galantamine), one NMDA-R antagonist (memantine), one combination therapy (memantine/donepezil), and GV-971 (sodium oligomannate, a mixture of oligosaccharides derived from algae) only approved in China. Improvements to the approved therapies, such as easier routes of administration and reduced dosing frequencies, along with the developments of new strategies and combined treatments are expected to occur within the next decade and will positively impact the way the disease is managed. Recently, Aducanumab, the first disease-modifying therapy (DMT) has been approved for AD, and several DMTs are in advanced stages of clinical development or regulatory review. Small molecules, mAbs, or multimodal strategies showing promise in animal studies have not confirmed that promise in the clinic (where small to moderate changes in clinical efficacy have been observed), and therefore, there is a significant unmet need for a better understanding of the AD pathogenesis and the exploration of alternative etiologies and therapeutic effective disease-modifying therapies strategies for AD. Therefore, a critical review of the disease-modifying therapy pipeline for Alzheimer’s disease is needed.
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“DMTs are intended to delay the progression of long-term conditions such as AD and ultimately improve the patient’s quality of life [60].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [60]
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“DMTs are treatments that postpone, moderate, or even reverse the evolution of an illness by addressing its underlying cause.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [60]
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Items 201–245 of 245
Pericytes: Problems and Promises for CNS Repair
Laredo, F., Plebanski, J., & Tedeschi, A. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00546 · Cited by 44 · cited 1×
“In these disorders, pericyte malfunction often leads to BBB disruption and/or a decrease of CBF, thus causing secondary neurological damage [180].”
BackgroundProkopenko, D., Hecker, J., Kirchner, R., Chapman, B., Hofmann, O., Mullin, K., Hide, W., Bertram, L., Laird, N. M., DeMeo, D. L., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-61883-6 · Cited by 44
Ávila‐Villanueva, M., & Fernández‐Blázquez, M. A. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00377 · Cited by 42
Cholesterol-lowering drugs reduce APP processing to Aβ by inducing APP dimerization
Langness, V. F., van der Kant, R., Das, U., Wang, L., Chaves, R. D. S., & Goldstein, L. S. B. (2021) · Molecular Biology of the Cell · doi:10.1091/mbc.e20-05-0345 · Cited by 41
The propagation mechanisms of extracellular tau in Alzheimer’s disease
Wei, Y., Liu, M., & Wang, D. (2021) · Journal of Neurology · doi:10.1007/s00415-021-10573-y · Cited by 40
Ettcheto, M., Sánchez‐López, E., Pons, L., Busquets, O., Olloquequi, J., Beas‐Zárate, C., Pallàs, M., García, M. L., Auladell, C., Folch, J., et al. (2017) · Redox Biology · doi:10.1016/j.redox.2017.06.003 · Cited by 39
Picón-Pagès, P., Bonet, J., Garcı́a-Garcı́a, J., Garcia-Buendia, J., Gutiérrez, D. A., Valle, J., Gómez-Casuso, C. E. S., Sidelkivska, V., Alvarez, A. R., Perálvarez‐Marín, A., et al. (2019) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2019.06.017 · Cited by 39
Alzheimer Disease: Standard of Diagnosis, Treatment, Care, and Prevention
Teipel, S. J., Gustafson, D., Ossenkoppele, R., Hansson, O., Babiloni, C., Wagner, M., Riedel-Heller, S. G., Kilimann, I., & Tang, Y. (2022) · Journal of Nuclear Medicine · doi:10.2967/jnumed.121.262239 · Cited by 39
Tailoring the Antibody Response to Aggregated Aß Using Novel Alzheimer-Vaccines
Mandler, M., Santic, R., Gruber, P., Cinar, Y., Pichler, D., Funke, S. A., Willbold, D., Schneeberger, A., SCHMIDT, W. A., & Mattner, F. (2015) · PLoS ONE · doi:10.1371/journal.pone.0115237 · Cited by 38
Muszyński, P., Kulczyńska‐Przybik, A., Borawska, R., Litman‐Zawadzka, A., Słowik, A., Klimkowicz‐Mrowiec, A., Pera, J., Dziedzic, T., & Mroczko, B. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170220 · Cited by 38
pGluAβ increases accumulation of Aβ in vivo and exacerbates its toxicity
Sofola-Adesakin, O., Khericha, M., Snoeren, I., Tsuda, L., & Partridge, L. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0380-x · Cited by 37
Central pharmacodynamic activity of solanezumab in mild Alzheimer's disease dementia
Willis, B. A., Sundell, K. L., Lachno, D. R., Ferguson‐Sells, L. R., Case, M. G., Holdridge, K. C., Demattos, R. B., Raskin, J., Siemers, E., & Dean, R. A. (2018) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.10.001 · Cited by 37
Sources of Extracellular Tau and its Signaling
Ávila, J., Simón, D., Díaz-Hernández, M., Pintor, J. J., & Hernández, F. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131832 · Cited by 36
N‐terminal heterogeneity of parenchymal and vascular amyloid‐β deposits in Alzheimer’s disease
Zampar, S., Klafki, H., Sritharen, K., Bayer, T. A., Wiltfang, J., Rostagno, A. A., Ghiso, J. A., Miles, L. A., & Wirths, O. (2020) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12637 · Cited by 36
Robinson, E., Tate, M., Lockhart, S. M., McPeake, C., O’Neill, K. M., Edgar, K. S., Calderwood, D., Green, B. D., McDermott, B. J., & Grieve, D. (2016) · Cardiovascular Diabetology · doi:10.1186/s12933-016-0386-5 · Cited by 35
Dalla, Y., Singh, N., Jaggi, A. S., & Singh, D. (2010) · Pharmacological Reports · doi:10.1016/s1734-1140(10)70339-x · Cited by 34
Gemtuzumab Ozogamicin for Treatment of Newly Diagnosed CD33-Positive Acute Myeloid Leukemia
Gbadamosi, M. O., Meshinchi, S., & Lamba, J. K. (2018) · Future Oncology · doi:10.2217/fon-2018-0325 · Cited by 34
An Anti-apoE4 Specific Monoclonal Antibody Counteracts the Pathological Effects of apoE4 In Vivo
Luz, I., Liraz, O., & M. Michaelson, D. (2016) · Current Alzheimer Research · doi:10.2174/1567205013666160404120817 · Cited by 33
The Interplay between Diabetes and Alzheimer’s Disease—In the Hunt for Biomarkers
Kubis-Kubiak, A., Dyba, A. J., & Piwowar, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082744 · Cited by 33
The Protective A673T Mutation of Amyloid Precursor Protein (APP) in Alzheimer’s Disease
Xia, Q., Yang, X., Shi, J., Liu, Z., Peng, Y., Wang, W., Li, B., Zhao, Y., Xiao, J., Huang, L. F., et al. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02385-y · Cited by 32
Emerging insights into the role of albumin with plasma exchange in Alzheimer’s disease management
Costa, M., & Páez, A. (2021) · Transfusion and Apheresis Science · doi:10.1016/j.transci.2021.103164 · Cited by 32
Increased glutaminyl cyclase activity in brains of Alzheimer’s disease individuals
Gunn, A. P., Wong, B. X. W., McLean, C., Fowler, C. J., Barnard, P. J., Duce, J. A., & Roberts, B. R. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15114 · Cited by 28
Peptide-Based Vaccines for Neurodegenerative Diseases: Recent Endeavors and Future Perspectives
Vassilakopoulou, V., Karachaliou, C., Evangelou, A., Zikos, C. C., & Livaniou, E. (2021) · Vaccines · doi:10.3390/vaccines9111278 · Cited by 27
Bouter, Y., Liekefeld, H., Pichlo, S., Westhoff, A. C., Fenn, L., Bakrania, P., & Bayer, T. A. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02418-3 · Cited by 26
Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial
Tufan, A. N., & Tufan, F. (2015) · Neurology · doi:10.1212/01.wnl.0000475736.75775.25 · Cited by 25
Ballard, C. G., Nørgaard, C. H., Friedrich, S., Mørch, L. S., Gerds, T. A., Møller, D. V., Knudsen, L. B., Kvist, K., Zinman, B., Holm, E., et al. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.042909 · Cited by 25
Sochocka, M., Ochnik, M., Sobczyński, M., Gębura, K., Zambrowicz, A., Naporowski, P., & Leszek, J. (2022) · Nutrients · doi:10.3390/nu14102022 · Cited by 25
Antonyan, A. A., Schlenzig, D., Schilling, S., Naumann, M., Sharoyan, S. G., Mardanyan, S. S., & Demuth, H. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.12.001 · Cited by 24
Rachdaoui, N., Polo‐Parada, L., & Ismail‐Beigi, F. (2018) · Journal of the Endocrine Society · doi:10.1210/js.2018-00140 · Cited by 24
Hannestad, J. O., Duclos, T., Chao, W., Koborsi, K., Klutzaritz, V., Beck, B., Patel, A. K., Scott, J., Thein, S., Cummings, J. L., et al. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210011 · Cited by 24
Hoffmann, T., Rahfeld, J., Schenk, M., Ponath, F., Makioka, K., Hutter‐Paier, B., Lues, I., Lemere, C. A., & Schilling, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111791 · Cited by 23
The protein inputs of an ultra-predictive aging clock represent viable anti-aging drug targets
Johnson, A. A., Shokhirev, M. N., & Lehallier, B. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101404 · Cited by 22 · cited 1×
“Two parallel processes occur simultaneously in our body during aging/AD: (i) products of pathophysiological processes in the AD brain are shown to diffuse to the blood and (ii) different waves of changes in the proteome appear during aging [220].”
BackgroundMeng, M., Di, A. I., Sun, L., Xu, X., & Cao, X. (2019) · Neuroreport · doi:10.1097/wnr.0000000000001223 · Cited by 21
Neddens, J., Daurer, M., Flunkert, S., Beutl, K., Loeffler, T., Walker, L., Attems, J., & Hutter‐Paier, B. (2020) · PLoS ONE · doi:10.1371/journal.pone.0235543 · Cited by 20
Brooks, A. F., Jackson, I. M., Shao, X., Kropog, G., Sherman, P. S., Quesada, C., & Scott, P. J. H. (2015) · MedChemComm · doi:10.1039/c5md00148j · Cited by 16
Safety and tolerability of GRF6019 in mild‐to‐moderate Alzheimer's disease dementia
Hannestad, J. O., Koborsi, K., Klutzaritz, V., Chao, W., Ray, R., Páez, A., Jackson, S., Lohr, S., Cummings, J. L., Kay, G. G., et al. (2020) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12115 · Cited by 16
Intracerebroventricular passive immunization in transgenic mouse models of Alzheimer’s disease
Chauhan, N. B., & Siegel, G. J. (2004) · Expert Review of Vaccines · doi:10.1586/14760584.3.6.717 · Cited by 15
Cuberas‐Borrós, G., Roca, I., Castell‐Conesa, J., Núñez, L., Boada, M., López, O. L., Grifols, C., Barceló, M., Pareto, D., & Páez, A. (2022) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-022-05915-5 · Cited by 14
Self-citationEttcheto, M., Sánchez‐López, E., Cano, A. C., Carrasco, M., Herrera, K., Manzine, P. R., Espinosa-Jiménez, T., Busquets, O., Verdaguer, E., Olloquequi, J., et al. (2021) · Cell & Bioscience · doi:10.1186/s13578-021-00646-w · Cited by 12
Şeyhanlı, A., Yavuz, B., Selimoğlu, İ., Şengün, İ. Ş., Aslan, T., Özsan, G. H., Alacacıoğlu, İ., & Demırkan, F. (2021) · Therapeutic Apheresis and Dialysis · doi:10.1111/1744-9987.13703 · Cited by 11
Willis, B. A., Lowe, S. L., Monk, S. A., Cocke, P. J., Aluise, C. D., Boggs, L. N., Borders, A. R., Brier, R. A., Dean, R. A., Green, S. J., et al. (2022) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-210037 · Cited by 8
Late-Onset Alzheimer's Disease: Risk Factors, Clinical Diagnosis and the Search for Biomarkers
Herrera-Rivero, M. (2013) · InTech eBooks · doi:10.5772/53775 · Cited by 7
Aisen, P. S., Schafer, K. A., Grundman, M., Pfeiffer, E., Sano, M., Davis, K. L., Farlow, M. R., Jin, S., Thomas, R. G., Thal, L. J., et al. (2003) · JAMA · doi:10.1001/jama.289.21.2819 · Cited by 5
Ortiz, A. M., Minguet, C., Gonzalo, R., Núñez, L., Ruiz, A., López, O. L., Boada, M., Páez, A., & Costa, M. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.057735 · Cited by 2
Self-citationHolstege, H. H., Hulsman, M., Charbonnier, C., Grenier‐Boley, B., Quenez, O., Grozeva, D., van Rooij, J., Sims, R., Ahmad, S., Amin, N., et al. (2021) · EUR Research Repository (Erasmus University Rotterdam) · doi:10.1002/alz.055982 · Cited by 1
Flagged first, then by citations
4 of the 249 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Renee, 2015, CSF1 receptor signaling is necessary for microglia viability, which unmasks a cell that rapidly repopulates the microglia-depleted adult brain, Neuron, 82, 380
- Xiao, 2021, Group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate, Alzheimer‘s Dement., 7, 1
Cited by
Sorted by citations
Zhang, J., Zhang, Y., Wang, J., Xia, Y., Zhang, J., & Chen, L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01911-3 · Cited by 1,138
Tang, B., Wang, Y., & Ren, J. (2023) · Ibrain · doi:10.1002/ibra.12098 · Cited by 129
Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease
Barmaki, H., Nourazarian, A., & Khaki‐Khatibi, F. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2023.1281338 · Cited by 97
Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease
Thawabteh, A. M., Ghanem, A. W., AbuMadi, S., Thaher, D., Jaghama, W., Karaman, D., & Karaman, R. (2024) · Molecules · doi:10.3390/molecules29215131 · Cited by 56
“DMTs are intended to delay the progression of long-term conditions such as AD and ultimately improve the patient’s quality of life [60].”
BackgroundHarnessing microalgae as sustainable cellular factories for biopharmaceutical production
Goshtasbi, H., Okolodkov, Y. B., Movafeghi, A., Awale, S., Safary, A., Barar, J., & Omidi, Y. (2023) · Algal Research · doi:10.1016/j.algal.2023.103237 · Cited by 47
Metadata
- Authors
- Morató, X., Pytel, V., Jofresa, S., Ruiz, A., & Boada, M.
- Affiliations
- Universitat Internacional de Catalunya (ES)
- Research Center and Memory Clinic, Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya, 08017 Barcelona, Spain
- Corresponding author
- Morató, Xavier
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2022-08-18
- Volume
- 23
- Issue
- 16
- Pages
- 9305
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC9409252
- OpenAlex
- W4292247066
- Cited by
- 53
- References
- 249
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 15 · 2023: 10 · 2022: 2
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, disease-modifying therapy, symptomatic treatment, drug development pipeline, polypharmacology, personalized medicine, amyloid-beta, tau hyperphosphorylation, cholinesterase inhibitors, memantine, aducanumab, anti-amyloid monoclonal antibodies, neuroinflammation
- MeSH terms
- Donepezil, Alzheimer Disease, Animals, Humans, Memantine, Amyloid beta-Peptides, Patient-Centered Care, Polypharmacology
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