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

IF 13 1区 医学 Q1 CLINICAL NEUROLOGY
Richa Batra, Jan Krumsiek, Xue Wang, Mariet Allen, Colette Blach, Gabi Kastenmüller, Matthias Arnold, Nilüfer Ertekin-Taner, Rima Kaddurah-Daouk, for the Alzheimer's Disease Metabolomics Consortium (ADMC)
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引用次数: 0

Abstract

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.

Abstract Image

脑代谢组学比较揭示了阿尔茨海默病和进行性核上性麻痹共同和独特的代谢改变
代谢失调是包括阿尔茨海默病(AD)和进行性核上性麻痹(PSP)在内的神经退行性疾病的特征。虽然代谢失调是这两种牛磺酸病之间的共同联系,但尚未对这两种疾病进行全面的脑代谢比较。
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来源期刊
Alzheimer's & Dementia
Alzheimer's & Dementia 医学-临床神经学
CiteScore
14.50
自引率
5.00%
发文量
299
审稿时长
3 months
期刊介绍: Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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