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Is Alzheimer disease a disease?

Nature Reviews Neurology volume 20, pages 245–251 (2024)Cite this article

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Abstract

Dementia, a prevalent condition among older individuals, has profound societal implications. Extensive research has resulted in no cure for what is perceived as the most common dementing illness: Alzheimer disease (AD). AD is defined by specific brain abnormalities — amyloid-β plaques and tau protein neurofibrillary tangles — that are proposed to actively influence the neurodegenerative process. However, conclusive evidence of amyloid-β toxicity is lacking, the mechanisms leading to the accumulation of plaques and tangles are unknown, and removing amyloid-β has not halted neurodegeneration. So, the question remains, are we making progress towards a solution? The complexity of AD is underscored by numerous genetic and environmental risk factors, and diverse clinical presentations, suggesting that AD is more akin to a syndrome than to a traditional disease, with its pathological manifestation representing a convergence of pathogenic pathways. Therefore, a solution requires a multifaceted approach over a single ‘silver bullet’. Improved recognition and classification of conditions that converge in plaques and tangle accumulation and their treatment requires the use of multiple strategies simultaneously.

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Acknowledgements

L.T.G. receives research support for the Rainwater Charitable Foundation and from the US National Institutes of Health (K24AG053435, R01AG060477, R01AG064314, R01AG070826, R01AG075802, U54NS123746, U01AG057195, U54AG065187, P30AG062422 and P01AG019724).

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Authors and Affiliations

  1. Departments of Neurology, Physiology and Pharmacology, Tel Aviv University, Tel Aviv, Israel

    Amos D. Korczyn

  2. Departments of Neurology and Pathology, UCSF, San Francisco, CA, USA

    Lea T. Grinberg

  3. Global Brain Health Institute, UCSF, San Francisco, CA, USA

    Lea T. Grinberg

  4. Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil

    Lea T. Grinberg

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Correspondence to Amos D. Korczyn.

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A.D.K. is the President of the World Congress on Controversies in Neurology. L.T.G. receives research support from Genentech Inc. and a gift from Pivotal Life Science; received honoraria for educational activities from Medscape Education, Celdara Medical and for consulting from Guidepoint Insights; and is a member of the Medical and Scientific Advisory Group for the Alzheimer’s Association.

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Korczyn, A.D., Grinberg, L.T. Is Alzheimer disease a disease?. Nat Rev Neurol 20, 245–251 (2024). https://doi.org/10.1038/s41582-024-00940-4

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