Alzheimer Disease: Ransmayr G

Ransmayr G, Katzenschlager R, Dal-Bianco P, Wenning G, Bancher C, Jellinger K, Schmidt R, Poewe W. · Neurologische Universitätsklinik Graz, Medizinische Universität Graz. · Neuropsychiatr. · Pubmed #17640492 No free full text.

Abstract: Dementia with Lewy Bodies (DLB) accounts for approximately 20 % of all autopsy-confirmed dementias in the elderly. Presumably, DLB is underdiagnosed in patients without or with only mild Parkinsonian symptoms in the daily routine of memory clinics. This motivated the Austrian Alzheimer Society and the Austrian Parkinson Society to inform about core features, suggestive features and supportive clinical findings of DLB and to provide information on diagnostic possibilities leading to better differential diagnosis. We also guide in the management of DLB as pharmacological treatment can pose difficult dilemmas for the treating clinician.

Schmidt R, Kienbacher E, Benke T, Dal-Bianco P, Delazer M, Ladurner G, Jellinger K, Marksteiner J, Ransmayr G, Schmidt H, Stögmann E, Friedrich J, Wehringer C. · Univ.-Klinik für Neurologie, Medizinische Universität Graz. · Neuropsychiatr. · Pubmed #18381051 No free full text.

Abstract: The prevalence of Alzheimer disease is higher in women than in men. In the age group 65-69 years 0.7% of women and 0.6% of men suffer from the disease with increasing frequencies of 14.2% and 8.8% in individuals aged 85-89 years. The incidence is also higher in demented women. In Austria 74.1% of Alzheimer patients older than 60 years are women. Several studies report more pronounced language, mnestic, semantic and orientation deficits in women, but methodological shortcomings might be responsible for this finding. The validity of results reporting a more rapid cognitive decline in women can also be questioned. Women have a broader spectrum of dementiarelated behavioural symptoms with a predominance of depression, while aggression is more frequent in men than in women. Biological explanations for gender-specific differences in the phenotype of Alzheimer s disease include different brain morphology and function with higher susceptibility for pathological lesions in women and greater cognitive reserve in men. Sex differences were also reported for expression of antioxidative enzymes and post-menopausal hormonal changes. Interactions between gender nd response to treatment, if any, are subtle and have large intra-individual variability. In Austria, two thirds of patients receiving attendance allowance are women. Care takes place in 80% by the families and is provided by women in 78%. The rate of female care-givers in partly institutionalized care units in 91% in nursing homes it is 84%.

Blasko I, Ransmayr G, Veerhuis R, Eikelenboom P, Grubeck-Loebenstein B. · Department of Neurology, University Hospital of Innsbruck, Innsbruck, Austria. · J Neuroimmunol. · Pubmed #11311323 No free full text.

This publication has no abstract.

Ransmayr G, Wenning GK, Seppi K, Jellinger K, Poewe W. · Universitätsklinik für Neurologie, Anichstrasse 35, A-6020 Innsbruck. · Nervenarzt. · Pubmed #11139988 No free full text.

Abstract: Dementia with Lewy bodies (DLB) is the second most frequent neuropathologically diagnosed degenerative dementing illness. The clinical characteristics are progressive dementia, parkinsonian syndrome, fluctuations of cognitive functions, alertness, and attention, visual hallucinations (usually detailed and well described), depression, REM sleep behavior disorder, adverse responses to standard neuroleptics doses, falls, syncopes, systematized delusions, and other modalities of hallucinations. Specificity of the clinical diagnostic criteria is high (95%), and sensitivity is considerably lower. Mean age at disease onset ranges between 60 and 68 years. The male gender prevails. Disease duration is 6 to 8 years. The differential diagnoses of DLB are dementia of the Alzheimer type, Parkinson's disease, subcortical arteriosclerotic encephalopathy, progressive supranuclear palsy, multiple system atrophy, and rarely Creutzfeldt-Jakob disease. The genetic background of the disease is unclear. Magnetic resonance imaging and single photon emission tomography can contribute to the diagnosis. Controlled pharmacological studies have so far not been published. The disease is treated with L-dopa, atypical neuroleptics, acetylcholine esterase inhibitors, antihypotensive agents, and peripheral anticholinergic and alpha receptor-blocking medications to improve neurogenic bladder dysfunction.

Brenneis C, Wenning GK, Egger KE, Schocke M, Trieb T, Seppi K, Marksteiner J, Ransmayr G, Benke T, Poewe W. · Department of Neurology, University Hospital of Innsbruck, Anichstr. 35, 6020 Innsbruck, Austria. · Neuroreport. · Pubmed #15257132 No free full text.

Abstract: We determined brain atrophy patterns in dementia with Lewy bodies and Alzheimer's disease using voxel-based morphometry, an indirect volumetry. Ten patients with dementia with Lewy bodies, 10 patients with Alzheimer's disease and 10 controls were included. All groups were matched for age; sex and global differences in voxel intensities were included as confounding covariates. We observed basal forebrain atrophy discriminating dementia with Lewy bodies from Alzheimer's disease. Compared to controls, atrophy of lateral prefrontal cortex and left premotor cortex was seen in dementia with Lewy bodies whereas atrophy of the medial temporal cortex, posterior parietal cortex, thalamus and temporo-occipital areas was observed in Alzheimer's disease. Atrophy of insular cortex was found in both patient groups.

Blasko I, Beer R, Bigl M, Apelt J, Franz G, Rudzki D, Ransmayr G, Kampfl A, Schliebs R. · Department of Psychiatry, University Hospital of Innsbruck, Innsbruck, Austria. · J Neural Transm. · Pubmed #15057522 No free full text.

Abstract: Traumatic brain injury (TBI) is a risk factor for the development of Alzheimer's disease (AD). After a traumatic brain injury depositions of amyloid beta (Abeta) in the brain parenchyma were found. In this study we investigated the expression pattern of beta-secretase (BACE-1) in ipsi- or contralateral hippocampus and cortex following controlled cortical TBI in rats. BACE-1 mRNA levels, estimated by real time RT-PCR, were elevated 24 h post injury, and persisting up to 72 h, in the ipsi- and contralateral hippocampus and cerebral cortex as compared to the sham-treated animals (p<0.01). The TBI-induced changes in BACE-1 mRNA are due to enhanced hippocampal and cortical expression of BACE-1 mRNA in neurons and reactive astrocytes as revealed by in situ hybridization. The alterations in hippocampal BACE-1 mRNA levels are accompanied by corresponding increases in BACE-1 protein levels in ipsi- and contralateral hippocampus and ipsilateral cortex as demonstrated by Western blot analysis. In contrast, in the contralateral cortex only a weak increase of traumatically induced BACE-1 protein production was found. The activity of BACE-1 as measured by the formation of the cleavage product of amyloid beta precursor protein, transiently increased up to 48 h after injury, but returned to basal level 7 days post injury. This study demonstrates that the beta-secretase is stimulated following TBI and may suggest a mechanism for the temporal increase of Abeta levels observed in patients with brain trauma.

Ransmayr G. · Neurologisch-psychiatrische Abteilung, Allgemeines Krankenhauses der Stadt Linz, Krankenhausstrasse 9, A-4020 Linz. · Wien Med Wochenschr. · Pubmed #12879635 No free full text.

Abstract: Two recent observational studies have demonstrated a 60-73% reduction in the prevalence of Alzheimer's disease in patients treated with statins. In two further studies a polymorphism in the CYP46 gene encoding the cholesterol-24 hydroxylase was found to be associated with a significant increase in the risk of late-onset Alzheimer's disease. The question arises whether or not statins may exert a prophylactic effect on the incidence of Alzheimer's disease. Statins pass the blood-brain-barrier to a different degree and may reduce the cerebral cholesterol turnover. Statins may also influence the CSF concentration of tau protein, and, to a minor extent, that of A beta. Further studies are warranted to find out which statins are most suitable for reducing cerebral amyloid metabolism and whether statins may also lower the severity of Alzheimer's disease.

Götz ME, Wacker M, Luckhaus C, Wanek P, Tatschner T, Jellinger K, Leblhuber F, Ransmayr G, Riederer P, Eder E. · Department of Toxicology, University of Würzburg, Germany. · Neurosci Lett. · Pubmed #11983292 No free full text.

Abstract: In recent years, an important role for the pathogenesis of Alzheimer's disease (AD) has been ascribed to oxidative stress. Trans-4-hydroxy-2-nonenal, a product of lipid peroxidation, forms stable adducts with a variety of nucleophilic substituents such as thiols or amino moieties. Here, we report the quantification of 1,N2-propanodeoxyguanosine adducts of trans-4-hydroxy-2-nonenal (HNE-dGp) using the specific and very sensitive method of 32P-postlabeling of deoxyguanosine adducts derived from nuclear DNA in neuron rich areas of the hippocampus, the parietal cortex, and the cerebellum of postmortem brains from patients with AD and age matched controls. Adduct levels were highest in the hippocampus, followed by the cerebellum and parietal cortex irrespective of the disease. Neither age, postmortem delay time, gender, nor the extent of neurofibrillary deposits affected tissue adduct levels in the brain areas examined. Although distinctively present in the human brain, the level of HNE-dGp adducts appears not to be useful as a biomarker for AD.

Ransmayr G. · Universitätsklinik für Neurologie, Anichstrasse 35, A-6020 Innsbruck. · Wien Med Wochenschr. · Pubmed #11925777 No free full text.

Abstract: Dementia with Lewy bodies (DLB) is the second most frequent neuropathologically diagnosed degenerative dementing illness. The clinical characteristics are progressive dementia, Parkinson syndrome, fluctuations of cognitive functions, vigilance and attention, visual hallucinations (usually detailed and well described), depression, REM-sleep behavior disorder, adverse responses to standard doses of neuroleptics, falls, syncopes, systematized delusions, and non-visual hallucinations. Mean age at disease onset ranges between 60 and 68 years. Male persons are more frequently affected than female. Disease duration is six to seven years. The differential diagnoses of DLB are dementia of the Alzheimer-type, Parkinson's disease, subcortical arteriosclerotic encephalopathy, progressive supranuclear palsy, multiple system atrophy, and, in rare cases, Creutzfeldt-Jakob disease. The genetic background of the disease is unclear. Magnetic resonance imaging and single photon emission tomography can contribute to the diagnosis. The disease is treated with L-dopa, atypical neuroleptics, acetylcholine esterase inhibitors, antihypotensive agents, and peripheral anticholinergic and alpha-receptor-blocking medicaments to improve neurogenic bladder dysfunction.

Blasko I, Apochal A, Boeck G, Hartmann T, Grubeck-Loebenstein B, Ransmayr G. · Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck, Austria. · Neurobiol Dis. · Pubmed #11741404 No free full text.

Abstract: Trying to decrease the production of Amyloid beta (Abeta) has been envisaged as a promising approach to prevent neurodegeneration in Alzheimer's disease (AD). A chronic inflammatory reaction with activated microglia cells and astrocytes is a constant feature of AD. The participation of the immune system in the disease process is further documented in several retrospective clinical studies showing an inverse relationship between the prevalence of AD and nonsteroidal anti-inflammatory drug (NSAID) therapy. Previously, we demonstrated that the combination of the proinflammatory cytokines TNFalpha with IFNgamma induces the production of Abeta-42 and Abeta-40 in human neuronal cells. In the present study, the neuronal cell line Sk-n-sh was incubated for 12 h with the cyclooxygenase inhibitor ibuprofen and subsequently stimulated with the cytokines TNFalpha and IFNgamma. Ibuprofen treatment decreased the secretion of total Abeta in the conditioned media of cytokine stimulated cells by 50% and prevented the accumulation of Abeta-42 and Abeta-40 in detergent soluble cell extracts. Viability of neuronal cells measured by detection of apoptosis was neither influenced by ibuprofen nor by cytokine treatment. The reduction in the production of Abeta by ibuprofen was presumably due to a decreased production of betaAPP, which in contrast to the control proteins M2 pyruvate kinase, beta-tubulin and the cytokine inducible ICAM-1 was detected at low concentration in ibuprofen treated cells. The data demonstrate a possible mechanism how ibuprofen may decrease the risk and delay the onset of AD.

Ransmayr G. · Department of Neurology, University of Innsbruck, Austria. · J Neural Transm Suppl. · Pubmed #11205149 No free full text.

Abstract: The article summarises history, terminology, the clinical and neuropathological diagnostic criteria, neurochemical and genetic findings, sensitivity and specificity of the clinical diagnostic criteria, prevalence, demographical data and nosology, differential diagnosis, and therapy of dementia with Lewy bodies (DLB). DLB shares clinical symptoms of Parkinson's disease and dementia of the Alzheimer-type (DAT). However, DLB is also different to PD and DAT (less tremor and asymmetry of the motor symptoms, more falls, and less favourable response to L-Dopa than PD; in contrast to DAT marked cognitive fluctuations and phases of reduced alertness, hallucinations and delirium). There are genetic similarities to DAT and PD in terms of common genetic risk factors. A genetic cause of the disease has so far not been detected. Whether or not DLB is a disease entity or an association of diseases (Lewy body disease and DAT) has so far not been elucidated. Clinical distinction from DAT and PD has clinical importance because of different therapeutic and prognostic implications. Studies are needed to standardize the treatment of motor, cognitive, psychiatric and vegetative symptoms.

Ransmayr G, Faucheux B, Nowakowski C, Kubis N, Federspiel S, Kaufmann W, Henin D, Hauw JJ, Agid Y, Hirsch EC. · Universitätsklinik für Neurologie, Anichstrasse 35, A-6020, Innsbruck, Austria. · Neurosci Lett. · Pubmed #10889341 No free full text.

Abstract: Cholinergic neurons in the basal forebrain and the upper brainstem undergo changes during aging and in dementia of the Alzheimer type, Parkinson's disease and progressive supranuclear palsy. Little is known about the effect of age on neurons in the tegmental pedunculopontine nucleus. Cholinergic neurons revealed by choline acetyltransferase immunohistochemistry were quantified in the brains of 20 subjects who died without neurological disorder between 28 and 101 years of age. A U-shaped relationship between cell counts and age was found, namely, a decrease in counts between 28 and 70, a minimum between 80 and 91 years of age, and, in four subjects aged 98-101 years counts comparable to those of subjects having died between 28 and 65 years. The findings suggest that the loss of cholinergic pedunculopontine nucleus neurons is not linear. In centenarians age-related neuronal decrease in pedunculopontine nucleus neurons may be slower or the stock of pedunculopontine nucleus neurons greater than in subjects dying earlier.

Gerlach M, Stadler K, Aichner F, Ransmayr G. · No affiliation provided · Neurology. · Pubmed #12427918 No free full text.

This publication has no abstract.