PuSH - Publikationsserver des Helmholtz Zentrums München: Comparative brain metabolomics reveals shared and distinct metabolic alterations in Alzheimer's disease and progressive supranuclear palsy.

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Batra, R.* ; Krumsiek, J.* ; Wang, X.* ; Allen, M.* ; Blach, C.* ; Kastenmüller, G. ; Arnold, M. ; Ertekin-Taner, N.* ; Kaddurah-Daouk, R.*

Comparative brain metabolomics reveals shared and distinct metabolic alterations in Alzheimer's disease and progressive supranuclear palsy.

Alzheimers Dement., DOI: 10.1002/alz.14249 (2024)

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BACKGROUND: Metabolic dysregulation is a hallmark of neurodegenerative diseases, including Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). Although metabolic dysregulation is a common link between these two tauopathies, a comprehensive brain metabolic comparison of the diseases has not yet been performed. METHODS: We analyzed 342 postmortem brain samples from the Mayo Clinic Brain Bank and examined 658 metabolites in the cerebellar cortex and the temporal cortex between the two tauopathies. RESULTS: Our findings indicate that both diseases display oxidative stress associated with lipid metabolism, mitochondrial dysfunction linked to lysine metabolism, and an indication of tau-induced polyamine stress response. However, specific to AD, we detected glutathione-related neuroinflammation, deregulations of enzymes tied to purines, and cognitive deficits associated with vitamin B. DISCUSSION: Our findings underscore vast alterations in the brain's metabolome, illuminating shared neurodegenerative pathways and disease-specific traits in AD and PSP. HIGHLIGHTS: First high-throughput metabolic comparison of Alzheimer's diesease (AD) versus progressive supranuclear palsy (PSP) in brain tissue. Cerebellar cortex (CER) shows substantial AD-related metabolic changes, despite limited proteinopathy. AD impacts both CER and temporal cortex (TCX); PSP's changes are primarily in CER. AD and PSP share metabolic alterations despite major pathological differences.

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