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Detection and treatment of Alzheimer’s disease in its preclinical stage

Nature Aging volume 3, pages 520–531 (2023)Cite this article

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Abstract

Longitudinal multimodal biomarker studies reveal that the continuum of Alzheimer’s disease (AD) includes a long latent phase, referred to as preclinical AD, which precedes the onset of symptoms by decades. Treatment during the preclinical AD phase offers an optimal opportunity for slowing the progression of disease. However, trial design in this population is complex. In this Review, we discuss the recent advances in accurate plasma measurements, new recruitment approaches, sensitive cognitive instruments and self-reported outcomes that have facilitated the successful launch of multiple phase 3 trials for preclinical AD. The recent success of anti-amyloid immunotherapy trials in symptomatic AD has increased the enthusiasm for testing this strategy at the earliest feasible stage. We provide an outlook for standard screening of amyloid accumulation at the preclinical stage in clinically normal individuals, during which effective therapy to delay or prevent cognitive decline can be initiated.

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Fig. 1: Continuum of Alzheimer’s disease over 25 years.
Fig. 2: Biomarkers and the amyloid, tau and neurodegeneration (ATN) classification.

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Acknowledgements

Funding support includes U24AG057437 to P.S.A.

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  1. Alzheimer’s Therapeutic Research Institute, Keck School of Medicine University of Southern California, Los Angeles, CA, USA

    Michael S. Rafii & Paul S. Aisen

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M.S.R. and P.S.A. contributed to writing this text.

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Competing interests

M.S.R. reports consulting for AC Immune, Alzheon, Aptah, Biohaven, Ionis and Keystone Bio and grants from the National Institute on Aging. P.S.A. received research support from Eisai, Eli Lilly, Janssen, the Alzheimer’s Association, the NIH and the FNIH and has consulted for ImmunoBrain Checkpoint, Merck and Roche.

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Rafii, M.S., Aisen, P.S. Detection and treatment of Alzheimer’s disease in its preclinical stage. Nat Aging 3, 520–531 (2023). https://doi.org/10.1038/s43587-023-00410-4

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