Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022
The landscape of metabolic brain alterations in Alzheimer's disease.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Batra Richa, Arnold Matthias, Wörheide Maria A, Allen Mariet, Wang Xue, Blach Colette, Levey Allan I, Seyfried Nicholas T, Ertekin-Taner Nilüfer, Bennett David A, Kastenmüller Gabi, Kaddurah-Daouk Rima F, Krumsiek Jan, Alzheimer's Disease Metabolomics Consortium (ADMC)
Аннотация
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.
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.