A phase II trial of the tau antibody semorinemab indicates that it has no clinical benefit in the earliest stages of Alzheimer disease. The repeated finding that antibody-mediated reductions in protein pathology have limited or no clinical benefit indicates that we need to consider more specific or combined therapeutic targets.
This is a preview of subscription content, access via your institution
Subscribe to Nature+
Get immediate online access to Nature and 55 other Nature journal
Subscribe to Journal
Get full journal access for 1 year
only $6.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Song, C. et al. Immunotherapy for Alzheimer’s disease: targeting β-amyloid and beyond. Transl. Neurodegener. 11, 18 (2022).
Teng, E. et al. Safety and efficacy of semorinemab in individuals with prodromal to mild Alzheimer disease: a randomized clinical trial. JAMA Neurol. (2022).
Panza, F. et al. Disease-modifying therapies for tauopathies: agents in the pipeline. Expert Rev. Neurother. 19, 397–408 (2019).
Asuni, A. A., Boutajangout, A., Quartermain, D. & Sigurdsson, E. M. Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. J. Neurosci. 27, 9115–9129 (2007).
Bowman Rogers, M. 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).
Lananna, B. V. et al. Chi3l1/YKL-40 is controlled by the astrocyte circadian clock and regulates neuroinflammation and Alzheimer’s disease pathogenesis. Sci. Transl. Med. 12, eaax3519 (2020).
Lee, S. H. et al. Antibody-mediated targeting of tau in vivo does not require effector function and microglial engagement. Cell Rep. 16, 1690–1700 (2016).
AC Immune announces late-breaker presentation by Genentech at CTAD on phase 2 Lauriet study of semorinemab in mild-to-moderate Alzheimer’s disease. https://ir.acimmune.com/news-releases/news-release-details/ac-immune-announces-late-breaker-presentation-genentech-ctad (2021).
Horie, K., Barthélemy, N. R., Sato, C. & Bateman, R. J. CSF tau microtubule binding region identifies tau tangle and clinical stages of Alzheimer’s disease. Brain 144, 515–527 (2021).
Ossenkoppele, R. et al. Accuracy of tau positron emission tomography as a prognostic marker in preclinical and prodromal Alzheimer disease: a head-to-head comparison against amyloid positron emission tomography and magnetic resonance imaging. JAMA Neurol. 78, 961–971 (2021).
The authors declare no competing interests.
About this article
Cite this article
Panza, F., Lozupone, M. The challenges of anti-tau therapeutics in Alzheimer disease. Nat Rev Neurol 18, 577–578 (2022). https://doi.org/10.1038/s41582-022-00702-0