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Bad news and good news in AD, and how to reconcile them

2018 saw the failure of several large clinical trials that were based on the premise that reduction of amyloid-β levels is an effective treatment for symptomatic Alzheimer disease. Yet, over the same time period, good news also emerged about the diagnostic value of tau PET imaging.

Key advances

  • Failures of anti-amyloid-β (Aβ) antibodies have highlighted gaps in understanding their dosing and the timing of their usage in the Alzheimer disease (AD) spectrum1,2.

  • The human clinical trials of BACE1 inhibitors cast doubt on this therapeutic approach but might provide valuable insights into the normal cellular and synaptic functions of Aβ and its precursor6.

  • Tau PET imaging shows excellent specificity and expected sensitivity for clinically diagnosed dementia with elevated Aβ8.

  • A new research framework offers researchers a common language for describing the Aβ, tau and neurodegeneration patterns of patients along the entire cognitive spectrum of AD10.

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This work was supported by NIH grants P50 AG16574, U01 AG06786 and R01 AG41851.

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Correspondence to David S. Knopman.

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Competing interests

D.S.K. serves on a Data Safety Monitoring Board (DSMB) for The Dominantly Inherited Alzheimer Network (DIAN) study for which he receives personal compensation. He serves on a DSMB for Biogen, but all compensation related to that activity goes to his institution. He is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals and the University of Southern California. He does not receive any personal compensation from either Biogen or Lilly as a site investigator; his institution receives funding for those activities. He is an adviser to Samus Pharmaceuticals and Alzeca Biosciences. For both, he receives no personal compensation; his institution receives funding for those activities. He receives research support from the NIH. Avid Radiopharmaceuticals, Inc., supplies Mayo Clinic with AV-1451 precursor, chemistry production advice and oversight, and FDA regulatory cross-filing permission and documentation that is used in research in which D.S.K. is an investigator.

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Knopman, D.S. Bad news and good news in AD, and how to reconcile them. Nat Rev Neurol 15, 61–62 (2019).

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