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The challenges of anti-tau therapeutics in Alzheimer disease

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.

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  1. Song, C. et al. Immunotherapy for Alzheimer’s disease: targeting β-amyloid and beyond. Transl. Neurodegener. 11, 18 (2022).

    Article  CAS  Google Scholar 

  2. Teng, E. et al. Safety and efficacy of semorinemab in individuals with prodromal to mild Alzheimer disease: a randomized clinical trial. JAMA Neurol. (2022).

  3. Panza, F. et al. Disease-modifying therapies for tauopathies: agents in the pipeline. Expert Rev. Neurother. 19, 397–408 (2019).

    Article  CAS  Google Scholar 

  4. 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).

    Article  CAS  Google Scholar 

  5. Bowman Rogers, M. N-terminal tau antibodies fade, mid-domain ones push to the fore. Alzforum (2021).

  6. 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).

    Article  CAS  Google Scholar 

  7. 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).

    Article  CAS  Google Scholar 

  8. AC Immune announces late-breaker presentation by Genentech at CTAD on phase 2 Lauriet study of semorinemab in mild-to-moderate Alzheimer’s disease. (2021).

  9. 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).

    Article  Google Scholar 

  10. 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).

    Article  Google Scholar 

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Correspondence to Francesco Panza.

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Panza, F., Lozupone, M. The challenges of anti-tau therapeutics in Alzheimer disease. Nat Rev Neurol 18, 577–578 (2022).

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