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Batra, R.* ; Arnold, M. ; Wörheide, M. ; Allen, M.* ; Wang, X.* ; Blach, C.* ; Levey, A.I.* ; Seyfried, N.T.* ; Ertekin-Taner, N.* ; Bennett, D.A.* ; Kastenmüller, G. ; Kaddurah-Daouk, R.F.* ; Krumsiek, J.*

The landscape of metabolic brain alterations in Alzheimer's disease.

Alzheimers Dement., DOI: 10.1002/alz.12714 (2022)
Postprint Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
INTRODUCTION: Alzheimer's disease (AD) is accompanied by metabolic alterations both in the periphery and the central nervous system. However, so far, a global view of AD-associated metabolic changes in the brain has been missing. METHODS: We metabolically profiled 500 samples from the dorsolateral prefrontal cortex. Metabolite levels were correlated with eight clinical parameters, covering both late-life cognitive performance and AD neuropathology measures. RESULTS: We observed widespread metabolic dysregulation associated with AD, spanning 298 metabolites from various AD-relevant pathways. These included alterations to bioenergetics, cholesterol metabolism, neuroinflammation, and metabolic consequences of neurotransmitter ratio imbalances. Our findings further suggest impaired osmoregulation as a potential pathomechanism in AD. Finally, inspecting the interplay of proteinopathies provided evidence that metabolic associations were largely driven by tau pathology rather than amyloid beta pathology. DISCUSSION: This work provides a comprehensive reference map of metabolic brain changes in AD that lays the foundation for future mechanistic follow-up studies.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Alzheimer's Disease ; Bioenergetic Pathways ; Brain ; Cholesterol Metabolism ; Metabolic Landscape ; Metabolism ; Multi-omic Integration ; Neuroinflammation ; Neurotransmission ; Osmoregulation
Language english
Publication Year 2022
HGF-reported in Year 2022
ISSN (print) / ISBN 1552-5260
e-ISSN 1552-5279
Journal Alzheimer's & Dementia
Publisher Elsevier
Publishing Place New York, NY [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503891-001
Grants Cure PSP and Mayo
NINDS NIH HHS
NIA NIH HHS
NIH HHS
DOI 10.1002/alz.12714
WOS ID WOS:000823728500001
Scopus ID 85133904861
PubMed ID 35829654
Erfassungsdatum 2022-09-30
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