Your search for: 'author:("Grünblatt, Edna")' has returned 8 results. (0.017s) Save search

Authors: Grünblatt, Edna | Koutsilieri, Eleni | Hoyer, Siegfried | Riederer, Peter

Article Type: Research Article

Abstract: Streptozotocin is well known inducer of experimental diabetes mellitus when injected peripherally. However, when administered intracerebroventricular, streptozotocin showed a whole spectrum of specific biochemical and behavioural alterations with regard to cognitive functions, feeding, nociception, brain glucose metabolism, neurotransmission and oxidative stress, without producing arterial hyperglycaemia, similarly to Alzheimer's disease. In order to reveal the mechanism of action of neurodegeneration in streptozotocin rat model we investigated the expression of several genes involved in inflammation, oxidative stress, growth- and transcription-factors in the cortex, striatum and cerebellum, using real-time quantitative RT-PCR. Genes such as GDNF, BDNF and integrin-alpha-M were up-regulated, while immediate-early-gene-transcription-factor NGF-IB …and metallothionein-1/2 were down-regulated in the cortex of streptozotocin-treated rats. Conversely, NGF-IB, GDNF and BDNF mRNA expression did not alter in the striatum and cerebellum. However, integrin alpha-M and metallothionein-1/2 expressions decreased significantly in the striatum and increased in the cerebellum. These gene changes may provide an insight into the cascade of physiological abnormalities following the inhibition of neuronal insulin signal transduction. Additionally, similarities to neuronal cell death in sporadic Alzheimer's disease may become apparent. Show more

Keywords: Alzheimer's disease, diabetes, insulin, neurodegeneration, quantitative-RT-PCR, rat, streptozotocin

DOI: 10.3233/JAD-2006-9305

Citation: Journal of Alzheimer's Disease, vol. 9, no. 3, pp. 261-271, 2006

Authors: Strobel, Sabrina | Grünblatt, Edna | Heinsen, Helmut | Riederer, Peter | Espach, Thomas | Meder, Michael | Monoranu, Camelia-Maria

Article Type: Research Article

Abstract: Oxidative stress is implicated in the pathogenesis of neurodegenerative diseases, including sporadic Alzheimer’s disease (AD). Mitochondrial DNA (mtDNA) deletions are markers of oxidative damage with an age-dependent accumulation. In a previous study, we analyzed mtDNA levels in diverse neuronal cell types in order to unravel the impact of oxidative stress in brains of AD patients. The aim of this study was to identify possible correlations between mtDNA deletion levels of selected astrocytes and microglia from three brain regions with different vulnerability to AD pathology and different stages of disease compared to controls. Our results reflect a higher vulnerability of hippocampal …astrocytes and microglia to oxidative stress compared to other brain regions, such as cerebellum and brainstem. Show more

Keywords: Alzheimer’s disease, astrocytes, brainstem, cerebellum, hippocampus, microglia, mitochondrial DNA, oxidative stress, selective vulnerability

DOI: 10.3233/JAD-180661

Citation: Journal of Alzheimer's Disease, vol. 67, no. 1, pp. 149-157, 2019

Authors: Salkovic-Petrisic, Melita | Osmanovic, Jelena | Grünblatt, Edna | Riederer, Peter | Hoyer, Siegfried

Article Type: Review Article

Abstract: Nosologically, Alzheimer's disease (AD) is not a single disorder. Missense gene mutations involved in increased formation of the amyloid-β protein precursor derivatives amyloid-β (Aβ)1-40 and Aβ1-42/43 lead to autosomal dominant familial AD, found in the minority of AD cases. However, millions of subjects suffer from sporadic AD (sAD) of late onset, for which no convincing evidence suggests Aβ as the primary disease-generating compound. Environmental factors operating during pregnancy and postnatally may affect susceptibility genes and stress factors (e.g., cortisol), consequently affecting brain development both structurally and functionally, causing diseases that only becoming manifest late in life. With aging, a desynchronization …of biological systems may result, increasing further brain entropy/declining criticality. In sAD, this desynchronization may involve stress components, cortisol and noradrenaline, reactive oxygen species, and membrane damage as major candidates causing an insulin resistant brain state with decreased glucose/energy metabolism. This further leads to a derangement of ATP-dependent cellular and molecular work, of the cell function in general, as well as derangements in the endoplasmic reticulum/Golgi apparatus, axon, synapses, and membranes, in particular. A self-propagating process is thus generated, including the increased formation of hyperphosphorylated tau-protein and Aβ as abnormal terminal events in sAD rather than causing the disorder, as elaborated in the review. Show more

Keywords: Amyloid-β, brain, hyperphosphorylated tau, insulin, insulin resistant brain state, oxidative metabolism, sporadic Alzheimer disease

DOI: 10.3233/JAD-2009-1184

Citation: Journal of Alzheimer's Disease, vol. 18, no. 4, pp. 729-750, 2009

Authors: Grünblatt, Edna | Bartl, Jasmin | Zehetmayer, Sonja | Ringel, Thomas M. | Bauer, Peter | Riederer, Peter | Jacob, Christian P.

Article Type: Research Article

Abstract: Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. At present, diagnosis of AD is rather late in the disease. Therefore, we attempted to find peripheral biomarkers for the early diagnosis of AD. We investigated the profiles of 33 genes, previously found by our group to have altered expression in postmortem brains of AD. The gene profiles were studied via quantitative-real-time-reverse-transcription-polymerase-chain-reaction, in whole blood samples (collected with the PAXgene™ blood RNA system) isolated from a population clinically diagnosed with AD and healthy controls (1-year period/ up to 4 samples). Five genes showed significant correlation to …the dementia score, Mini-Mental State Examination (MMSE). Focusing on the two genes with the smallest p-value, H3-histone and cannabinoid-receptor-2, notable increases in these genes were found in peripheral blood mRNA in subjects with lower MMSE scores. Seasonal variations in gene expression were not significant due to sample size, but did seem to vary due to time of sample withdrawal. In conclusion, gene expression profiling might be a promising method to investigating a large population with the aim of developing an early diagnosis of AD. Show more

Keywords: Alzheimer's disease, biomarker, cannabinoid receptor, diagnose, gene expression, histone

DOI: 10.3233/JAD-2009-0996

Citation: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 627-634, 2009

Authors: Michel, Tanja Maria | Gsell, Wieland | Käsbauer, Ludwig | Tatschner, Thomas | Sheldrick, Abigail Jane | Neuner, Irene | Schneider, Frank | Grünblatt, Edna | Riederer, Peter

Article Type: Research Article

Abstract: For decades, it has been acknowledged that oxidative stress due to free radical species contributes to the pathophysiology of aging and neurodegenerative diseases. Aldehyde dehydrogenases (ALDH) not only transform aldehydes to acids but also act as antioxidant enzymes. However, little is known about the implications of the enzymatic family of ALDH in the context of neurodegenerative processes such as Alzheimer's disease (AD). We therefore examined the enzymatic activity of the mitochondrial ALDH-isoform in different regions of the postmortem brain tissue isolated from patients with AD and controls. We found that the mitochondrial ALDH activity was significantly increased only in the …putamen of patients suffering from AD compared to controls. This is of particular interest since mediators of oxidative stress, such as iron, are increased in the putamen of patients with AD. This study adds to the body of evidence that suggests that oxidative stress as well as aldehyde toxicity play a role in AD. Show more

Keywords: Aging, aldehydehydrogenase, Alzheimer's disease, dementia, free radicals, mitochondria, oxidative stress

DOI: 10.3233/JAD-2010-1326

Citation: Journal of Alzheimer's Disease, vol. 19, no. 4, pp. 1295-1301, 2010

Authors: Reif, Andreas | Grünblatt, Edna | Herterich, Sabine | Wichart, Ildiko | Rainer, Michael K. | Jungwirth, Susanne | Danielczyk, Walter | Deckert, Jürgen | Tragl, Karl-Heinz | Riederer, Peter | Fischer, Peter

Article Type: Research Article

Abstract: NO synthase, type I (NOS-I) has been suggested to play a role in the etiology of Alzheimer's disease (AD). The gene encoding NOS-I harbors at least nine alternative first exons; in the promoter region of exon 1f, a polymorphic repeat (NOS1 ex1f-VNTR) has been described which influences gene expression and neuronal transcriptome. We have shown that short alleles of this repeat are associated with AD. Here, we sought to further explore this finding by investigating a longitudinal cohort sample from the Vienna-Transdanube-Aging (VITA) study consisting of 606 subjects enrolled at the age of 75 (of these, genotypes were available for …574 subjects) and followed up for 60 months. The ex1f-VNTR risk genotype was associated with AD in the total sample and at the second follow-up. Thus, either long alleles of NOS1 ex1f-VNTR are protective against disease or conversely, short alleles predispose to earlier onset of disease. As demonstrated, ex1f-VNTR interacted with the apolipoprotein E ε4 risk allele (OR in the presence of both risk alleles 3.63; 95% CI: 1.45–9.12). These findings provide further evidence for an association of NOS1 with AD. Show more

Keywords: Alzheimer's disease, genetics, neuronal nitric oxide synthase (NOS1), polymorphism, risk factor, VITA study

DOI: 10.3233/JAD-2010-101491

Citation: Journal of Alzheimer's Disease, vol. 23, no. 2, pp. 327-333, 2011

Authors: Grünblatt, Edna | Zander, Nicole | Bartl, Jasmin | Jie, Li | Monoranu, Camelia-Maria | Arzberger, Thomas | Ravid, Rivka | Roggendorf, Wolfgang | Gerlach, Manfred | Riederer, Peter

Article Type: Research Article

Abstract: Sporadic Alzheimer's (AD) and Parkinson's disease (PD) are late-onset neurodegenerative diseases with tremendous impact on lives of affected individuals. There is a great probability of developing concurrent Parkinsonism in AD and vice-versa than would be predicted by independent prevalence of each disease. We hypothesize that in sporadic AD as well as PD a combination of environmental effects and gene expression may affect specific brain areas leading to neurodegeneration. We profiled gene expression of AD compared to PD and age matched controls post-mortem in the hippocampus, the gyrus-frontalis-medius (Gfm) and the cerebellum using Gene-Chip microarray (Affymetrix) and quantitative-real-time-RT-PCR. Twelv genes altered …in similar manner in AD and PD, while four genes showed differential expression profiles between AD and PD in different brain regions (cannabinoid-receptor-2, Histone-cluster-1-H3e, nicotinic-cholinergic-receptor-α6 and β-site-APP-cleaving enzyme-1). Knowledge of selective gene expression profile can lead to better understanding of disease pathology and development of specific diagnosis and effective therapy. Show more

Keywords: Alzheimer's disease, affymetrix, gene chip, gene expression, microarray, Parkinson's disease, Quantitative-RT-PCR

DOI: 10.3233/JAD-2007-12402

Citation: Journal of Alzheimer's Disease, vol. 12, no. 4, pp. 291-311, 2007

Authors: Gerschütz, Anne | Heinsen, Helmut | Grünblatt, Edna | Wagner, Anne Kristin | Bartl, Jasmin | Meissner, Christoph | Fallgatter, Andreas J. | Al-Sarraj, Safa | Troakes, Claire | Ferrer, Isidro | Arzberger, Thomas | Deckert, Jürgen | Riederer, Peter | Fischer, Matthias | Tatschner, Thomas | Monoranu, Camelia Maria

Article Type: Research Article

Abstract: The hallmarks of sporadic Alzheimer's disease (AD) are extracellular amyloid deposits, intracellular neurofibrillary tangles (NFTs), and neuronal death. Hyperphosphorylation of tau is a key factor in the generation of NFTs. Mitogen activated protein kinase 1 (MAPK1) and protein kinase C beta (PRKCB) are thought to play a role in hyperphosphorylation, and PRCKB is thought to be involved in hypoxic stress and vascular dysfunction, and to trigger MAPK phosphorylation pathways. We performed single-cell analyses of neurons with different vulnerabilities to AD-related changes. Using quantitative PCR (qPCR), we measured the levels of MAPK1 and PRKCB transcript in CA1 (high vulnerability), CA2 pyramidal …cells from the hippocampus, granule cells from the cerebellum (low vulnerability), and neurons from the brain stem (nucleus tractus spinalis nervi trigemini, characterized by early neurophysiological deficits) at progressive Braak stages compared to age-matched controls. The highly vulnerable CA1 pyramidal neurons were characterized by age- and disease-unrelated increases in PRCKB levels and by age- and disease-related increases in MAPK1 levels. In contrast, low PRKCB levels were found in CA2 pyramidal neurons, and MAPK1 levels were elevated in controls and intermediate AD stages. Both PRKCB and MAPK1 were increased in the late AD stages. MAPK1 and PRKCB levels were low in the brainstem and cerebellum. We propose that alterations in the expression of these two genes occur early in the pathogenesis of AD in a region-specific manner. In addition, multiple signal transduction pathways need to be affected to result in AD instead of physiological aging. Show more

Keywords: Alzheimer's disease, MAPK1, neurodegeneration, PRKCB, selective vulnerability, signal transduction pathway

DOI: 10.3233/JAD-131280

Citation: Journal of Alzheimer's Disease, vol. 40, no. 1, pp. 135-142, 2014