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Jianqiu Kou,
Gabor G. Kovacs,
Romana Höftberger,
Willem Kulik,
Alexander Brodde,
Sonja Forss-Petter, Selma Hönigschnabl,
Andreas Gleiss,
Britta Brügger,
Ronald Wanders,
Wilhelm Just,
Herbert Budka,
Susanne Jungwirth,
Peter Fischer,
Johannes Berger
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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.
KeywordsAging–Neurofibrillary tangles–Peroxisome–Plasmalogen–VLCFA
Acta Neuropathologica 04/2012; 122(3):271-283. · 9.32 Impact Factor
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Jianqiu Kou,
Gabor G Kovacs,
Romana Höftberger,
Willem Kulik,
Alexander Brodde,
Sonja Forss-Petter, Selma Hönigschnabl,
Andreas Gleiss,
Britta Brügger,
Ronald Wanders,
Wilhelm Just,
Herbert Budka,
Susanne Jungwirth,
Peter Fischer,
Johannes Berger
[show abstract]
[hide abstract]
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.
Acta Neuropathologica 05/2011; 122(3):271-83. · 9.32 Impact Factor
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[show abstract]
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ABSTRACT: Sporadic tauopathies are characterized by differential cellular and topographical predominance of phospho-tau immunoreactivity and biochemical distinction of the tau protein. Established entities include progressive supranuclear palsy, corticobasal degeneration, Pick's disease, and argyrophilic grain disease. During a community-based longitudinal study on aging, we detected tau pathologies not compatible with these categories. We immunostained for different phospho-tau epitopes, 4R and 3R tau isoforms, α-synuclein, amyloid-β, and phospho-TDP-43, analyzed the MAPT and ApoE genes, and performed western blotting for the tau protein. The mean age of patients (4 women, 3 men) was 83.8 years. Clinical presentations combined dementia with psychiatric symptoms and/or parkinsonism. In addition to neurofibrillary tangles and diffuse neuronal cytoplasmic tau immunoreactivity, the neuropathology was characterized by peculiar cytopathologies (diffuse granular immunopositivity of astrocytic processes and patchy accumulation of thin threads) in a distinctive distribution (frontal and temporal cortices, hippocampus, amygdala, basal ganglia, locus coeruleus, and substantia nigra). Argyrophilic grains were detected in four patients. Few to moderate densities of neuritic plaques but widespread phospho-TDP-43 pathology was observed in five patients. There was variability in the H1/H2 and ApoE alleles and biochemical features of tau protein. We propose these cases as complex tauopathy with a characteristic constellation: some features of primary tauopathies and Alzheimer's disease mixed with additional cytopathologies including a distinctive astrogliopathy, in a characteristic distribution of lesions. These complex tauopathies in the elderly deserve specific diagnostic and eventually therapeutic considerations.
Acta Neuropathologica 03/2011; 122(2):205-22. · 9.32 Impact Factor
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ABSTRACT: This study examines the quality of street heroin seized in Vienna in 1999 and whether there was a relationship between the purity of street heroin and the number of heroin-related emergencies as well as the number of heroin-related deaths. Street heroin confiscated by the Viennese police, run-sheets of drug-related emergencies, and postmortem reports of drug-related deaths in Vienna in 1999 were analyzed. A total of 415 retail samples with a total weight of 128.02 g contained a median percentage of 6.5% diacetylmorphine (range: 0.0-47.0%). All the samples contained a diluent, mainly lactose, as well as adulterants, such as caffeine and/or paracetamol. During the study period, 75 heroin-related deaths and 387 heroin-related emergencies were registered in Vienna. Time-series analysis revealed no statistically significant relationship between the rate of heroin-related incidents and the diacetylmorphine concentration of street heroin samples confiscated in Vienna in 1999. The widely held belief that the number of heroin-related deaths could be explained simply through fluctuations in the purity of street heroin could not be substantiated, even though the results of this study do not rule out an association between the purity of heroin and heroin-related deaths/emergencies.
Journal of Forensic Sciences 10/2007; 52(5):1171-6. · 1.23 Impact Factor
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ABSTRACT: The cause of preferential metastatic spreading to cervical lymph nodes in oral squamous cell cancer (SCC) is not quite clear. As the density of microvessels may influence the metastatic behaviour, we were interested in how the density of blood/lymphatic microvessels are related to primary SCC and the clinical course of the disease.
Lymphatic and blood microvessels of 28 patients with oral SCC were identified immunohistochemically by antibodies against podoplanin and CD34, respectively. Lymphatic microvessel density (LVD) and blood microvessel density (MVD), and the expression of VEGF-C were determined. These findings were compared with the long-term clinicopathological data of the patients.
LVD and MVD were significantly higher than in control tissues. The amount of lymphatic microvessels correlated positively with the expression of VEGF-C, the tumour grade, the nodal status and with later appearing metastasis. The latter three parameters, however, did not influence the clinical course of the disease.
VEGF-C expression in oral SCC triggers lymphatic angiogenesis, which may result in a higher risk for cervical lymph node metastasis. The angiogenetic effect of VEGF-C may also favour the onset of late lymphatic and haematogenous metastases.
Journal of Oral Pathology and Medicine 10/2003; 32(8):455-60. · 1.63 Impact Factor
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ABSTRACT: Mass media reports attribute the occurrence of decomposed or mummified corpses in a domestic setting mainly to an increasing social isolation of elderly people. Not much is known about the demographic and medical conditions under which individuals are found months or even years after death in their homes. For this study, autopsy reports of individuals found dead and mummified or decomposed between 1993 and 1997 with those from 1963 to 1967 were retrospectively analyzed. Between 1993 and 1997, a total number of 320 individuals were found decomposed at home compared to 412 such cases between 1963 and 1967. The proportion of individuals older than 64 years was significantly higher during the 1990s study period. Furthermore, the proportion of deaths attributable to natural causes was significantly lower during the 1990s, whereas the rate of suicides was nearly three times higher.
Journal of Forensic Sciences 08/2002; 47(4):837-42. · 1.23 Impact Factor
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ABSTRACT: The purpose of this study was to update a long-term study that evaluates the accuracy of MR imaging in the characterisation of adrenal tumours. In all patients, MR imaging findings were correlated with histopathologic results.
In 204/560 patients who underwent MR imaging for characterisation of an adrenal mass, histopathologic results were available. The final study group consisted of 229 adrenal masses in 204 patients. MR imaging was performed using T2-weighted fast spin-echo imaging and unenhanced and gadolinium-enhanced T1-weighted spin-echo imaging in all patients. In addition, chemical shift imaging was performed in 182 patients and dynamic gadolinium-enhanced studies in 198 patients. Chemical shift images and dynamic studies were qualitatively assessed. All images were reviewed by an experienced investigator (Gertraud Heinz-Peer) who was blinded to the clinical history and the results of prior imaging studies.
The sensitivity of MR imaging for the differentiation of benign and malignant adrenal masses was 89%, the specificity 99%, and the accuracy was 93.9%. This results in a positive predictive value (PPV) of 90.9% and a negative predictive value (NPV) of 94.2%. These results are comparable to the data published previously by our study group with a lower number of cases.
Large study numbers show that MR imaging is a reliable method in characterisation of benign and malignant adrenal masses. Since laparoscopic adrenalectomy has become the new gold standard in the surgical treatment of benign adrenal lesions, the high accuracy of MR imaging in characterisation of those lesions offers even patients with large adrenal masses (>5 cm) the advantages of the minimally invasive technique.
European Journal of Radiology 03/2002; 41(2):113-22. · 2.61 Impact Factor
