Metabolomic Signatures of Alzheimer’s Disease Indicate Brain Region-Specific Neurodegenerative Progression

Autor: Mirela Ambeskovic, Giselle Hopkins, Tanzi Hoover, Jeffrey T. Joseph, Tony Montina, Gerlinde A. S. Metz
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 24, Iss 19, p 14769 (2023)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms241914769
Popis: Pathological mechanisms contributing to Alzheimer’s disease (AD) are still elusive. Here, we identified the metabolic signatures of AD in human post-mortem brains. Using 1H NMR spectroscopy and an untargeted metabolomics approach, we identified (1) metabolomic profiles of AD and age-matched healthy subjects in post-mortem brain tissue, and (2) region-common and region-unique metabolome alterations and biochemical pathways across eight brain regions revealed that BA9 was the most affected. Phenylalanine and phosphorylcholine were mainly downregulated, suggesting altered neurotransmitter synthesis. N-acetylaspartate and GABA were upregulated in most regions, suggesting higher inhibitory activity in neural circuits. Other region-common metabolic pathways indicated impaired mitochondrial function and energy metabolism, while region-unique pathways indicated oxidative stress and altered immune responses. Importantly, AD caused metabolic changes in brain regions with less well-documented pathological alterations that suggest degenerative progression. The findings provide a new understanding of the biochemical mechanisms of AD and guide biomarker discovery for personalized risk prediction and diagnosis.
Databáze: Directory of Open Access Journals
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