title: Peroxisomal alterations in Alzheimer's disease.
abstract: In Alzheimer's disease (AD), lipid alterations are present early during disease progression. As some of these alterations point towards a peroxisomal dysfunction, we investigated peroxisomes in human postmortem brains obtained from the cohort-based, longitudinal Vienna-Transdanube Aging (VITA) study. Based on the neuropathological Braak staging for AD on one hemisphere, the patients were grouped into three cohorts of increasing severity (stages I-II, III-IV, and V-VI, respectively). Lipid analyses of cortical regions from the other hemisphere revealed accumulation of C22:0 and very long-chain fatty acids (VLCFA, C24:0 and C26:0), all substrates for peroxisomal β-oxidation, in cases with stages V-VI pathology compared with those modestly affected (stages I-II). Conversely, the level of plasmalogens, which need intact peroxisomes for their biosynthesis, was decreased in severely affected tissues, in agreement with a peroxisomal dysfunction. In addition, the peroxisomal volume density was increased in the soma of neurons in gyrus frontalis at advanced AD stages. Confocal laser microscopy demonstrated a loss of peroxisomes in neuronal processes with abnormally phosphorylated tau protein, implicating impaired trafficking as the cause of altered peroxisomal distribution. Besides the original Braak staging, the study design allowed a direct correlation between the biochemical findings and the amount of neurofibrillary tangles (NFT) and neuritic plaques, quantified in adjacent tissue sections. Interestingly, the decrease in plasmalogens and the increase in VLCFA and peroxisomal volume density in neuronal somata all showed a stronger association with NFT than with neuritic plaques. These results indicate substantial peroxisome-related alterations in AD, which may contribute to the progression of AD pathology.
authors: Center for Brain Research, Medical University of Vienna, Vienna, Austria.
authors: Jianqiu
authors: J
authors: Kou
authors: Gabor G
authors: GG
authors: Kovacs
authors: Romana
authors: R
authors: Höftberger
authors: Willem
authors: W
authors: Kulik
authors: Alexander
authors: A
authors: Brodde
authors: Sonja
authors: S
authors: Forss-Petter
authors: Selma
authors: S
authors: Hönigschnabl
authors: Andreas
authors: A
authors: Gleiss
authors: Britta
authors: B
authors: Brügger
authors: Ronald
authors: R
authors: Wanders
authors: Wilhelm
authors: W
authors: Just
authors: Herbert
authors: H
authors: Budka
authors: Susanne
authors: S
authors: Jungwirth
authors: Peter
authors: P
authors: Fischer
authors: Johannes
authors: J
authors: Berger
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