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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 Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Alzheimer's Disease ; Bioenergetic Pathways ; Brain ; Cholesterol Metabolism ; Metabolic Landscape ; Metabolism ; Multi-omic Integration ; Neuroinflammation ; Neurotransmission ; Osmoregulation
ISSN (print) / ISBN 1552-5260
e-ISSN 1552-5279
Zeitschrift Alzheimer's & Dementia
Verlag Elsevier
Verlagsort New York, NY [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
Förderungen Cure PSP and Mayo
NINDS NIH HHS
NIA NIH HHS
NIH HHS