Early biochemical and morphological modifications in the brain of a transgenic mouse model of Alzheimer's disease: A role for peroxisomes

Annamaria Cimini, Sandra Moreno, Marcello D'Amelio, Loredana Cristiano, Barbara D'Angelo, Stefano Falone, Elisabetta Benedetti, Paolo Carrara, Francesca Fanelli, Francesco Cecconi, Fernanda Amicarelli, Maria Paola Cerù

Research output: Contribution to journalArticle

Abstract

The central role of peroxisomes in reactive oxygen species and lipid metabolism and their importance in brain functioning are well established. The aim of this work has been to study the peroxisomal population in the Tg2576 mouse model of Alzheimer's disease (AD), at the age of three months when no apparent signs of behavioral, neuroanatomical, cytological, or biochemical alterations have been so far described. The expression and localization of peroxisomal (PMP70, CAT, AOX, and THL) and peroxisome-related proteins (PEX5p, GPX1, SOD1, and SOD2) were studied in the neocortex and hippocampus of transgenic and wild-type animals. Oxidative stress markers (TBARS, acrolein, and 8-OHG) were also evaluated. Our results demonstrate that significant alterations are already detectable at this early stage of the disease and also involve peroxisomes. Their number and protein composition change concomitantly with early oxidative stress. Interestingly, the neocortex shows a compensatory response, consisting in an increase of reactive oxygen species scavenging enzymes, while the hippocampus appears more prone to the oxidative insult. This different behavior could be related to metabolic differences in the two brain areas, also involving peroxisome abundance and/or enzymatic content.

Original languageEnglish
Pages (from-to)935-952
Number of pages18
JournalJournal of Alzheimer's Disease
Volume18
Issue number4
DOIs
Publication statusPublished - 2009

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Keywords

  • Acyl-CoA β-oxidation
  • Alzheimer's disease
  • Antioxidant enzymes
  • Catalase
  • Hippocampus
  • Neocortex
  • Oxidative stress
  • Peroxisomes
  • Reactive oxygen species
  • Tg2576

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Cite this

Cimini, A., Moreno, S., D'Amelio, M., Cristiano, L., D'Angelo, B., Falone, S., Benedetti, E., Carrara, P., Fanelli, F., Cecconi, F., Amicarelli, F., & Cerù, M. P. (2009). Early biochemical and morphological modifications in the brain of a transgenic mouse model of Alzheimer's disease: A role for peroxisomes. Journal of Alzheimer's Disease, 18(4), 935-952. https://doi.org/10.3233/JAD-2009-1199