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Neuroinflammation Biomarkers in the AT(N) Framework Across the Alzheimer’s Disease Continuum

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Abstract

In the past years, neuroinflammation has been widely investigated in Alzheimer’s disease (AD). Evidence from animal, in vivo and post-mortem studies has shown that inflammatory changes are a common feature of the disease, apparently happening in response to amyloid-beta and tau accumulation. Progress in imaging and fluid biomarkers now allows for identifying surrogate markers of neuroinflammation in living individuals, which may offer unprecedented opportunities to better understand AD pathogenesis and progression. In this context, inflammatory mediators and glial proteins (mainly derived from microglial cells and astrocytes) seem to be the most promising biomarkers. Here, we discuss the biological basis of neuroinflammation in AD, revise the proposed neuroinflammation biomarkers, describe what we have learned from anti-inflammatory drug trials, and critically discuss the potential addition of these biomarkers in the AT(N) framework.

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Acknowledgement and Funding

ERZ serves in the scientific advisory board of Next Innovative Therapeutics (Nintx). The other authors declare that they have no competing interests. We thank Marco De Bastiani from Universiade Federal do Rio Grande do Sul for the fruitful discussion and for revising the final draft. P.R-N and SG are funded by Colin J. Adair Charitable Foundation, THE Weston Brain Institute, Canadian Institutes of Health Research (CIHR) [MOP-11-51-31; RFN 152985, 159815, 162303], Canadian Consortium of Neurodegeneration and Aging (CCNA; MOP-11-51-31 -team 1), the Alzheimer’s Association [NIRG-12-92090, NIRP-12-259245], Brain Canada Foundation (CFI Project 34874; 33397), the Fonds de Recherche du Québec — Santé (FRQS; Chercheur Boursier, 2020-VICO-279314). ERZ is funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) [#312410/2018- 2; #435642/2018-9; #312306/2021-0; 409066/2022-2]; Fundação de Amparo a pesquisa do Rio Grande do Sul (FAPERGS) [21/2551-0000673-0]; Alzheimer’s Association [AARGD-21-850670]; Alzheimer’s Association and National Academy of Neuropsycology [ALZ-NAN-22-928381].

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  1. Graduate Program in Biological Sciences: Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil, 90035-003

    A. Bieger, A. Rocha, B. Bellaver, L. Machado, L. Da Ros &  Eduardo R. Zimmer

  2. Department of Neurology and Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA

    B. Bellaver & T. A. Pascoal

  3. Graduate Program in Biological Sciences: Pharmacology and Therapeutics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    W. V. Borelli &  Eduardo R. Zimmer

  4. Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer’s Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l’Ouest-de-l’Île-de-Montréal; Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montreal, Canada

    J. Therriault, A. C. Macedo, S. Gauthier & P. Rosa-Neto

  5. Department of Neurology and Neurosurgery, McGill University, Montréal, Québec, Canada

    J. Therriault, A. C. Macedo, S. Gauthier, P. Rosa-Neto &  Eduardo R. Zimmer

  6. Montreal Neurological Institute, Montréal, Québec, Canada

    J. Therriault, A. C. Macedo, S. Gauthier & P. Rosa-Neto

  7. Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Eduardo R. Zimmer

  8. Brain Insitute of Rio Grande do Sul, PUCRS, Porto Alegre, Brazil

    Eduardo R. Zimmer

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  1. A. Bieger
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Conflict of interest: ERZ serves in the scientific advisory board of Next Innovative Therapeutics (Nintx). The other authors declare that they have no competing interests.

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Bieger, A., Rocha, A., Bellaver, B. et al. Neuroinflammation Biomarkers in the AT(N) Framework Across the Alzheimer’s Disease Continuum. J Prev Alzheimers Dis 10, 401–417 (2023). https://doi.org/10.14283/jpad.2023.54

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