Despite negative findings from numerous clinical trials of potential disease-modifying therapies for Alzheimer disease, amyloid remains the most compelling therapeutic target. Advances in biomarker methods now enable accurate monitoring of Alzheimer disease progression from the earliest stages of the disease. We must therefore redouble efforts to find an effective treatment.
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References
Selkoe, D. J. & Hardy, J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol. Med. 8, 595–608 (2016).
Cummings, J. L., Morstorf, T. & Zhong, K. Alzheimer’s disease drug-development pipeline: few candidates, frequent failures. Alzheimers Res. Ther. 6, 37–43 (2014).
Knopman, D. S. Lowering of amyloid-β by β-secretase inhibitors — some informative failures. N. Engl. J. Med. 380, 1476–1478 (2019).
Donohue, M. C. et al. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA 317, 2305–2316 (2017).
Klein, G. et al. Gantenerumab reduces amyloid-β plaques in patients with prodromal to moderate Alzheimer’s disease: a PET substudy interim analysis. Alzheimers Res. Ther. 11, 101 (2019).
Salloway, S. et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N. Engl. J. Med. 370, 322–333 (2014).
Moussa-Pacha, N. M., Abdin, S. M., Omar, H. A., Alniss, H. & Al-Tel, T. H. BACE1 inhibitors: Current status and future directions in treating Alzheimer’s disease. Med. Res. Rev. 40, 339–384 (2020).
Jonsson, T. et al. A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline. Nature 488, 96–99 (2012).
Arboleda-Velasquez, J. F. et al. Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report. Nat. Med. 25, 1680–1683 (2019).
Ulland, T. K. & Colonna, M. TREM2 - a key player in microglial biology and Alzheimer disease. Nat. Rev. Neurol. 14, 667–675 (2018).
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M.S.R. has served as consultant to AC Immune. P.S.A. has received research support from Lilly, Janssen, Eisai, the Alzheimer’s Association, NIH and FNIH, and has consulted for Merck, Biogen, Roche and ImmunoBrain Checkpoint.
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Rafii, M.S., Aisen, P.S. The search for Alzheimer disease therapeutics — same targets, better trials?. Nat Rev Neurol 16, 597–598 (2020). https://doi.org/10.1038/s41582-020-00414-3
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DOI: https://doi.org/10.1038/s41582-020-00414-3
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