The DOI matches its Crossref record; 380 of the 380 references it cites were found in a registry or an index.
Tau-targeting therapies for Alzheimer disease: current status and future directions
Open accessAbstract
Alzheimer disease (AD) is the most common cause of dementia in older individuals. AD is characterized pathologically by amyloid-β (Aβ) plaques and tau neurofibrillary tangles in the brain, with associated loss of synapses and neurons, which eventually results in dementia. Many of the early attempts to develop treatments for AD focused on Aβ, but a lack of efficacy of these treatments in terms of slowing disease progression led to a change of strategy towards targeting of tau pathology. Given that tau shows a stronger correlation with symptom severity than does Aβ, targeting of tau is more likely to be efficacious once cognitive decline begins. Anti-tau therapies initially focused on post-translational modifications, inhibition of tau aggregation and stabilization of microtubules. However, trials of many potential drugs were discontinued because of toxicity and/or lack of efficacy. Currently, the majority of tau-targeting agents in clinical trials are immunotherapies. In this Review, we provide an update on the results from the initial immunotherapy trials and an overview of new therapeutic candidates that are in clinical development, as well as considering future directions for tau-targeting therapies.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Research has indicated that tau pathology has a stronger correlation with cognitive deficits than Aβ plaques, indicating that treatment benefits from targeting tau may outweigh those from concentrating only on amyloid clearance [94,95].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [94]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Masliah, E., Rockenstein, E. M., Mante, M., Crews, L. A., Spencer, B. J., Adame, A., Patrick, C., Trejo, M., Ubhi, K. K., Rohn, T. T., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019338 · Cited by 422
RetractedAmyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Lecanemab in early Alzheimer's disease
van Dyck, C. H., Swanson, C. J., Aisen, P., Bateman, R. J., Chen, C., Gee, M., Kanekiyo, M., Li, D., Reyderman, L., Cohen, S., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2212948 · Cited by 5,678
Nichols, E., Steinmetz, J. D., Vollset, S. E., Fukutaki, K., Chalek, J., Abd-Allah, F., Abdoli, A., Abualhasan, A., Abu-Gharbieh, E., Akram, T. T., et al. (2022) · The Lancet Public Health · doi:10.1016/s2468-2667(21)00249-8 · Cited by 5,575
Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?
Leng, F., & Edison, P. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-020-00435-y · Cited by 3,179
Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., & Del Tredici, K. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0127-z · Cited by 3,172
Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial
Sims, J. R., Zimmer, J. A., Evans, C. D., Lu, M., Ardayfio, P., Sparks, J., Wessels, A. M., Shcherbinin, S., Wang, H., Monkul Nery, E. S., et al. (2023) · JAMA · doi:10.1001/jama.2023.13239 · Cited by 2,932
Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.3.631 · Cited by 2,668
2022 Alzheimer's disease facts and figures
Anonymous (2022) · Alzheimer s & Dementia · doi:10.1002/alz.12638 · Cited by 2,469
Curcumin as “Curecumin”: From kitchen to clinic
Goel, A., Kunnumakkara, A. B., & Aggarwal, B. B. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.08.016 · Cited by 2,274
Research works printed but not linked: 19
- Alzforum. Antisense therapy stifles CSF tau in mild Alzheimer’s disease. Alzforum https://www.alzforum.org/news/conference-coverage/antisense-therapy-stifles-csf-tau-mild-alzheimers-disease-0 (2021).
- Alzforum. First hit on aggregated tau: antisense oligonucleotide lowers tangles. Alzforum https://www.alzforum.org/news/conference-coverage/first-hit-aggregated-tau-antisense-oligonucleotide-lowers-tangles (2023).
- Ryan, J. M. et al. Phase 1 study in healthy volunteers of the O-GlcNAcase inhibitor ASN120290 as a novel therapy for progressive supranuclear palsy and related tauopathies [abstract O1-12-05]. Alzheimers Dement. 14 (7S Part 4), 251 (2018).
- Shcherbinin, S. et al. Brain target occupancy of LY3372689, an inhibitor of the O‐GlcNAcase (OGA) enzyme: translation from rat to human: neuroimaging/evaluating treatments. Alzheimers Dement. 16, e040558 (2020).
- Alzforum. Tau inhibitor fails again – subgroup analysis irks clinicians at CTAD. Alzforum https://www.alzforum.org/news/conference-coverage/tau-inhibitor-fails-again-subgroup-analysis-irks-clinicians-ctad (2016).
- Alzforum. In first phase 3 trial, the Tau drug LMTM did not work. Period. Alzforum http://www.alzforum.org/news/conference-coverage/first-phase-3-trial-tau-drug-lmtm-did-not-work-period#show-more (2016).
- Alzforum. First round of FTD therapeutics fell short, but many more are up and running. Alzforum https://www.alzforum.org/news/conference-coverage/first-round-ftd-therapeutics-fell-short-many-more-are-and-running (2016).
- Boutajangout, A., Ingadottir, J., Davies, P. & Sigurdsson, E. M. Passive tau immuntherapy diminishes functional decline and clears tau aggregates in a mouse model of tauopathy [abstract P3-427]. Alzheimers Dement. 6 (4S Part 19), S578 (2010).
- Alzforum. Active tau vaccine: hints of slowing neurodegeneration. Alzforum https://www.alzforum.org/news/conference-coverage/active-tau-vaccine-hints-slowing-neurodegeneration (2020).
- UCB. UCB presents UCB0107 anti-Tau immunotherapy Phase I study Results at World Movement Disorders Conference®. UCB https://www.ucb.com/stories-media/Press-Releases/article/UCB-presents-UCB0107-anti-Tau-immunotherapy-Phase-I-study-results-at-World-Movement-Disorders-Conference (2019).
- Alzforum. N-terminal tau antibodies fade, mid-domain ones push to the fore. Alzforum https://www.alzforum.org/news/conference-coverage/n-terminal-tau-antibodies-fade-mid-domain-ones-push-fore (2021).
- Alzforum. More tau antibodies bid adieu; semorinemab keeps foot in door. Alzforum https://www.alzforum.org/news/conference-coverage/more-tau-antibodies-bid-adieu-semorinemab-keeps-foot-door (2021).
- Eisai. Eisai presents data showing quantification of tau microtubule binding region in cerebrospinal fluid and the identification of a target engagement biomarker for the new anti-tau antibody E2814 at Alzheimer’s Association International Conference (AAIC) 2019. Eisai https://www.eisai.com/news/2019/news201955.html (2019).
- Horie, K. et al. Quantification of the tau microtubule binding region (MTBR) in cerebrospinal fluid and subsequent validation of target engagement assay for E2814, a novel anti-tau therapeutic antibody. Alzheimers Dement. 15(7S Part 31), 1598–1599 (2019).
- Zhou, J. et al. E2814: an anti-tau therapy engages its CNS target and affects the downstream tangle-specific biomarker MTBR-tau243 in dominantly inherited Alzheimer’s disease [abstract]. Presented at the Alzheimer’s Association International Conference, Amsterdam, Netherlands, and Online 2023 (2023).
- Rawal, S. et al. Safety, pharmacokinetics and immunogenicity of single and multiple ascending doses of the anti-tau therapeutic antibody E2814: a phase 1, first-in-human (FIH) study in healthy subjects [abstract P1-909]. Presented at the Alzheimer’s Association International Conference, Amsterdam, Netherlands, and Online (2023).
- Galpern, W. R. et al. A single ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the anti-phospho-tau antibody JNJ-63733657 in healthy subjects [abstract P1-052]. Alzheimers Dement. 15 (7S Part 5), 252–253 (2019).
- Prothena. Prothena reports topline phase 1 single ascending dose study results of PRX005, a novel anti-MTBR-tau antibody for the potential treatment of Alzheimer’s disease. Prothena https://ir.prothena.com/investors/press-releases/news-details/2023/Prothena-Reports-Topline-Phase-1-Single-Ascending-Dose-Study-Results-of-PRX005-a-Novel-Anti-MTBR-Tau-Antibody-for-the-Potential-Treatment-of-Alzheimers-Disease/default.aspx (2023).
- Martenyi, F. et al. PRX005, a novel anti-MTBR tau monoclonal antibody: results from a first-in-human double-blind, placebo-controlled, single ascending dose phase 1 study [abstract P1-727]. Presented at the Alzheimer’s Association International Conference, Amsterdam, Netherlands, and Online (2023).
Cited by
Sorted by citations
Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy
Zheng, Q., & Wang, X. (2024) · Protein & Cell · doi:10.1093/procel/pwae026 · Cited by 483
Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines
Xiao, W., Jiang, W., Chen, Z., Huang, Y., Mao, J., Zheng, W., Hu, Y., & Shi, J. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02107-5 · Cited by 449
Terao, I., & Kodama, W. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102203 · Cited by 137
Tau in neurodegenerative diseases: molecular mechanisms, biomarkers, and therapeutic strategies
Zhang, X., Wang, J., Zhang, Z., & Ye, K. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00429-6 · Cited by 119
Pathological mechanisms and treatment progression of Alzheimer’s disease
Zhang, J., Kong, G., Yang, J., Pang, L., & Li, X. (2025) · European journal of medical research · doi:10.1186/s40001-025-02886-9 · Cited by 111
Metadata
- Authors
- Congdon, E. E., Ji, C., Tetlow, A. M., Jiang, Y., & Sigurdsson, E. M.
- Affiliations
- New York University (US)
- NYU Langone Health (US)
- Corresponding author
- Sigurdsson, Einar M.
- Venue
- Nature Reviews Neurology
- Published
- 2023-10-24
- Volume
- 19
- Issue
- 12
- Pages
- 715-736
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- PMC
- PMC10965012
- OpenAlex
- W4387904363
- Cited by
- 371
- References
- 380
- Citations by year
- 2026: 125 · 2025: 170 · 2024: 74 · 2023: 1
- FWCI
- 13.17
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Alzheimer's Association (AG032611, AARF-22-924783)
- National Institutes of Health (NS120488)
- National Institute on Aging (R21AG069475, R01AG032611, T32AG052909)
- National Institute of Neurological Disorders and Stroke (RF1NS120488, R01NS120488, R01NS077239)
- 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
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, tau protein, tau immunotherapy, tau aggregation, microtubule stabilization, post-translational modification, amyloid plaques, neurofibrillary tangles, clinical trials, drug candidates
- MeSH terms
- Aged, Alzheimer Disease, Humans, Immunotherapy, Amyloid beta-Peptides, Neurofibrillary Tangles, tau Proteins, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
