Proteome-wide analysis identifies plasma immune regulators of amyloid-beta progression.

Alzheimer’s disease Amyloid-beta Positron emission tomography Proteomics

Journal

Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478

Informations de publication

Date de publication:
06 Jul 2024
Historique:
received: 04 04 2024
revised: 07 06 2024
accepted: 04 07 2024
medline: 9 7 2024
pubmed: 9 7 2024
entrez: 8 7 2024
Statut: aheadofprint

Résumé

While immune function is known to play a mechanistic role in Alzheimer's disease (AD), whether immune proteins in peripheral circulation influence the rate of amyloid-β (Aβ) progression - a central feature of AD - remains unknown. In the Baltimore Longitudinal Study of Aging, we quantified 942 immunological proteins in plasma and identified 32 (including CAT [catalase], CD36 [CD36 antigen], and KRT19 [keratin 19]) associated with rates of cortical Aβ accumulation measured with positron emission tomography (PET). Longitudinal changes in a subset of candidate proteins also predicted Aβ progression, and the mid- to late-life (20-year) trajectory of one protein, CAT, was associated with late-life Aβ-positive status in the Atherosclerosis Risk in Communities (ARIC) study. Genetic variation that influenced plasma levels of CAT, CD36 and KRT19 predicted rates of Aβ accumulation, including causal relationships with Aβ PET levels identified with two-sample Mendelian randomization. In addition to associations with tau PET and plasma AD biomarker changes, as well as expression patterns in human microglia subtypes and neurovascular cells in AD brain tissue, we showed that 31 % of candidate proteins were related to mid-life (20-year) or late-life (8-year) dementia risk in ARIC. Our findings reveal plasma proteins associated with longitudinal Aβ accumulation, and identify specific peripheral immune mediators that may contribute to the progression of AD pathophysiology.

Identifiants

DOI: 10.1016/j.bbi.2024.07.002 PMID: 38977137
pubmed: 38977137
pii: S0889-1591(24)00471-9
doi: 10.1016/j.bbi.2024.07.002
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: H.Z. has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). K.B. has served as a consultant and at advisory boards for Acumen, ALZPath, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd, Novartis, Ono Pharma, Prothena, Roche Diagnostics, and Siemens Healthineers, has served at data monitoring committees for Julius Clinical and Novartis, has given lectures, produced educational materials and participated in educational programs for AC Immune, Biogen, Celdara Medical, Eisai and Roche Diagnostics, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. R.M. has scientific collaborations with Alector, Nodthera and Alchemab, and has been consultant for Sanofi. B.D.S. is or has been a consultant for Eli Lilly, Biogen, Janssen Pharmaceutica, Eisai, AbbVie and other companies. B.D.S is also a scientific founder of Augustine Therapeutics and a scientific founder and stockholder of Muna Therapeutics.

Auteurs

Michael R Duggan (MR)

Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

Gabriela T Gomez (GT)

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Cassandra M Joynes (CM)

Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

Murat Bilgel (M)

Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

Jingsha Chen (J)

Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

Nicola Fattorelli (N)

VIB Center for Brain and Disease Research, Flanders Institute for Biotechnology, Leuven, Belgium; Department of Neurosciences and Leuven Brain Institute, KU Leuven, Leuven, Belgium.

Timothy J Hohman (TJ)

Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.

Renzo Mancuso (R)

Microglia and Inflammation in Neurological Disorders Laboratory, Center for Molecular Neurology, Flanders Institute for Biotechnology, Antwerp, Belgium; Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.

Jenifer Cordon (J)

Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

Tonnar Castellano (T)

Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.

Mary Ellen I Koran (MEI)

Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.

Julián Candia (J)

Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

Alexandria Lewis (A)

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abhay Moghekar (A)

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Nicholas J Ashton (NJ)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK; NIHR Biomedical Research Center for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK; Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.

Przemysław R Kac (PR)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden.

Thomas K Karikari (TK)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Kaj Blennow (K)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; ICM Institute, Pitié-Salpêtrière University Hospital, Sorbonne University, Paris, France; First Affiliated Hospital, University of Science and Technology of China, Anhui, PR China.

Henrik Zetterberg (H)

Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, University College London Institute of Neurology, London, UK; UK Dementia Research Institute, University College London, London, UK; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong Special Administrative Region; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.

Anna Martinez-Muriana (A)

VIB Center for Brain and Disease Research, Flanders Institute for Biotechnology, Leuven, Belgium; Department of Neurosciences and Leuven Brain Institute, KU Leuven, Leuven, Belgium.

Bart De Strooper (B)

VIB Center for Brain and Disease Research, Flanders Institute for Biotechnology, Leuven, Belgium; Department of Neurosciences and Leuven Brain Institute, KU Leuven, Leuven, Belgium; UK Dementia Research Institute, University College London, London, UK.

Madhav Thambisetty (M)

Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

Luigi Ferrucci (L)

Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

Rebecca F Gottesman (RF)

Stroke Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.

Josef Coresh (J)

Departments of Population Health and Medicine, New York University Grossman School of Medicine, New York, NY, USA.

Susan M Resnick (SM)

Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.

Keenan A Walker (KA)

Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. Electronic address: keenan.walker@nih.gov.

Classifications MeSH