Brain energy metabolism and neurodegeneration: hints from CSF lactate levels in dementias

Chiara Giuseppina Bonomi, Vincenzo De Lucia, Alfredo Paolo Mascolo, Martina Assogna, Caterina Motta, Eugenia Scaricamazza, Fabrizio Sallustio, Nicola Biagio Mercuri, Giacomo Koch, Alessandro Martorana

Research output: Contribution to journalArticlepeer-review

Abstract

Mitochondrial dysfunction is pivotal in the development of neurodegenerative dementias, causing cellular death alongside disease-specific pathogenic cascades. Holding cerebrospinal fluid (CSF) lactates as an indirect measure of brain metabolic activity, we first compared CSF lactate levels from patients with Alzheimer's disease (AD)—stratified according to the ATN system and epsilon genotype—frontotemporal dementia (FTD) and dementia with Lewy body (DLB) to findings from healthy controls. With respect to controls, we detected lower CSF lactates in patients with AD and FTD but comparable levels in patients with DLB. Second, a correlation analysis between CSF lactates and biomarkers of neurodegeneration identified an inverse correlation between lactates and levels of t-tau and p-tau only in the Alzheimer's continuum. The reduction of CSF lactate correlates to the advent of tauopathy and cellular death in AD, implying that Aβ pathology alone is not sufficient to induce neuronal metabolic impairment. The metabolic impairment in FTD patients has a similar explanation, as it is likely due to fast neuronal degeneration in the disease. The absence of CSF lactate reduction in patients with DLB may be related to the prevalent subcortical localization of the pathology.

Original languageEnglish
Pages (from-to)333-339
Number of pages7
JournalNeurobiology of Aging
Volume105
DOIs
Publication statusPublished - Sep 2021

Keywords

  • Alzheimer's continuum
  • Biomarkers
  • CSF lactates
  • Metabolic impairment
  • Neurodegenerative dementias

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology

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