Metabolomic and lipidomic signatures in autosomal dominant and late-onset Alzheimer's disease brains.

Autor:	Novotny BC; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA., Fernandez MV; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA., Wang C; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA.; Division of Biology & Biomedical Sciences, Washington University in St. Louis, St. Louis, Missouri, USA., Budde JP; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA., Bergmann K; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA., Eteleeb AM; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA., Bradley J; Division of Biology & Biomedical Sciences, Washington University in St. Louis, St. Louis, Missouri, USA., Webster C; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA., Ebl C; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA., Norton J; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA., Gentsch J; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA., Dube U; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA., Wang F; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA., Morris JC; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; The Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA., Bateman RJ; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; The Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA., Perrin RJ; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; The Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA., McDade E; Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA., Xiong C; The Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA., Chhatwal J; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Goate A; Icahn School of Medicine at Mount Sinai, New York, New York, USA., Farlow M; Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA., Schofield P; Neuroscience Research Australia, Randwick, Sydney, NSW, Australia., Chui H; Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Karch CM; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA., Cruchaga C; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA.; The Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA., Benitez BA; Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA., Harari O; Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri, USA.; NeuroGenomics and Informatics Center, Washington University School of Medicine, St. Louis, Missouri, USA.; The Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.
Jazyk:	angličtina
Zdroj:	Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2023 May; Vol. 19 (5), pp. 1785-1799. Date of Electronic Publication: 2022 Oct 17.
DOI:	10.1002/alz.12800
Abstrakt:	Introduction: The identification of multiple genetic risk factors for Alzheimer's disease (AD) suggests that many pathways contribute to AD onset and progression. However, the metabolomic and lipidomic profiles in carriers of distinct genetic risk factors are not fully understood. The metabolome can provide a direct image of dysregulated pathways in the brain. Methods: We interrogated metabolomic signatures in the AD brain, including carriers of pathogenic variants in APP, PSEN1, and PSEN2 (autosomal dominant AD; ADAD), APOE ɛ4, and TREM2 risk variant carriers, and sporadic AD (sAD). Results: We identified 133 unique and shared metabolites associated with ADAD, TREM2, and sAD. We identified a signature of 16 metabolites significantly altered between groups and associated with AD duration. Discussion: AD genetic variants show distinct metabolic perturbations. Investigation of these metabolites may provide greater insight into the etiology of AD and its impact on clinical presentation. Highlights: APP/PSEN1/PSEN2 and TREM2 variant carriers show distinct metabolic changes. A total of 133 metabolites were differentially abundant in AD genetic groups. β-citrylglutamate is differentially abundant in autosomal dominant, TREM2, and sporadic AD. A 16-metabolite profile shows differences between Alzheimer's disease (AD) genetic groups. The identified metabolic profile is associated with duration of disease. (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze:	MEDLINE
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