Shedding light on human cerebral lipofuscin: An explorative study on identification and quantification

Karlijn Hakvoort*, Louise Otto, Roel Haeren, Govert Hoogland, Olaf Schijns, Hans Vink, Dionne Klein, Marc van Zandvoort, Kim Rijkers

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Increased oxidative stress has been associated with several neurodegenerative diseases such as Alzheimer's disease, but also with neurological diseases sharing pathophysiological pathways like epilepsy. Lipofuscin is a nondegradable end-product of oxidative stress; its cerebral presence reflects the cumulative amount of oxidative stress the brain has endured. In this study, we have observed prominent autofluorescent particles in the pial arterial wall and in neocortical parenchyma of young, drug-resistant epilepsy patients (18-28 years old) who underwent resective brain surgery (n= 6), as well as in older control patients (n= 3). With fluorescence spectroscopic imaging, brightfield microscopy, histochemistry and fluorescence lifetime imaging, these autofluorescent particles were identified as theage pigmentlipofuscin. An evaluation of these lipofuscin particles using Imaris (c) software allowed robust quantification, while the 3D properties allowed visualization of the complex configuration. We elaborate on the usefulness of lipofuscin as a marker of cumulative oxidative stress in the brain. Furthermore, we speculate on the observed differences in particle size and density that we found between young patients and older controls, which could imply a role for lipofuscin in the pathophysiology of epilepsy and possibly other neurological diseases.

Original languageEnglish
Pages (from-to)605-615
Number of pages11
JournalJournal of Comparative Neurology
Volume529
Issue number3
Early online date19 Sep 2020
DOIs
Publication statusPublished - Feb 2021

Keywords

  • biomarker
  • epilepsy
  • Imaris
  • RRID:SCR_007370
  • lipofuscin
  • oxidative stress
  • quantification
  • BLOOD-BRAIN-BARRIER
  • OXIDATIVE STRESS
  • MITOCHONDRIAL DYSFUNCTION
  • LIPID-PEROXIDATION
  • ACCUMULATION
  • AGE
  • BIOMARKER
  • EPILEPSY

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