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K A Jellinger

Publications and source records attributed to K A Jellinger.

At least 19 recordsLinked to original sources
PubMed2006

Neurofibrillary tangle-predominant dementia: comparison with classical Alzheimer disease.

Neurofibrillary tangle predominant dementia (NFTPD) is a subset of late onset dementia, clinically different from traditional "plaque and tangle" Alzheimer disease (AD): later onset, shorter duration, less severe cognitive impairment, and almost absence of ApoE epsilon4. Neuropathology reveals abundant allocortical neurofibrillary pathology with no or few isocortical tau lesions, absence of neuritic plaques, absence or scarcity of amyloid deposits, but neurofibrillary changes comprising both 3 and 4 repeat (3R and 4R) tau immunohistochemistry are not significantly different from those in classical AD. Comparing 51 autopsy cases of NFTPD with 244 classical AD subjects, the nosology of NFTPD and its differences from AD are discussed.

Aged↗
PubMed2006

Alzheimer 100--highlights in the history of Alzheimer research.

Alzheimer disease, a progressive neurodegenerative disorder of hitherto unknown etiology leading progressively to severe incapacity and death, has become the pandemic of the 21(st) century. On World Alzheimer Day, September 21, 2006, the 100(th) anniversary of the first description of the clinical and histological findings in this disorder by A. Alzheimer, was celebrated. This retrospective review of the most important events and advances in Alzheimer research presents its early history in which only clinical and histologic signs of this peculiar disease were described. Electron microscopy, quantitative morphology and modern biochemistry emerging in the second half of the 20(th) century opened a new era in dementia research with description of the ultrastructure and biochemistry of senile plaques and neurofibrillary tangles, the major disease markers of AD. Advances in the development of clinical, neuropathological, and neuroimaging criteria, modern instruments and algorithms in the diagnosis of the disorder followed, enabling long-term studies and more exact diagnosis of AD and related disorders. Landmark studies were the development of operational criteria for the post mortem diagnosis of AD based on semiquantitative assessment and developmental patterns of its major markers. Basic research gave insight into the molecular genetics and pathophysiology of AD, and, based on the biochemical findings, new pharmacological treatment options were opened. Recently, biological and other surrogate, in particular functional neuroimaging, markers allow an early detection of presymptomatic stages of AD, their risk factors and progression which, in the future, might be prevented or at least slowed by new therapeutic approaches. Since the etiology of AD is hitherto unknown, causative therapies are still not available. The paper discusses future research needs and challenges for developing new diagnostic strategies for early and accurate detection of neurodegenerative processes leading to dementia, better epidemiologic and gender data as well as more insights into the pathogenic cascade of AD and other dementing disorders which will depend on international networks and close cooperation between clinicians, neuroscientists, caregivers, public health institutions, and individual sponsors.

Alzheimer Disease↗
PubMed2006

The morphological basis of mental dysfunction in Parkinson's disease.

Mental dysfunction including dementia in Parkinson's disease (PD), the incidence of which averages 20-40%, is suggested to have six-fold lifetime risk compared to age-matched controls. It is caused by a variety of functional and pathological lesions ranging from damage to subcortical-cortical networks to cortical and limbic Lewy body and neuritic Alzheimer pathologies, the relationship and impact of which are still under discussion. Based on two consecutive autopsy series of PD, with prevalence of cognitive impairment of 33% to 35.7%, its essential morphological changes and their impact on the natural history (survival) are discussed. Whereas cortical Lewy body stages 5 and 6 without additional pathologies only rarely were associated with dementia, around 20% of demented PD cases were classified as dementia with Lewy bodies (DLB) with variable degrees of Alzheimer (AD) pathology, and around one third showed severe neuritic AD lesions which occurred in PD patients with later disease onset and significantly shorter survival. Frequent close relations in the severity between alpha-synuclein and tau-pathologies suggest synergistic reaction and common underlying pathogenesis of both lesions. Clinico-pathological studies in PD showed a significantly negative relation between cognitive impairment and neuritic AD lesions somewhat different from that in AD, suggesting that neuritic AD pathology, either alone or in combination with cortical and limbic Lewy bodies, are major causes of mental and cognitive dysfunction in PD.

Aged↗
PubMed2006

A short history of neurosciences in Austria.

Based on internal medicine and psychiatry and in close connection with pathology, the neurosciences in Austria began to develop in the 18(th) century, e.g. with the description of inflammation of the central nervous system by J. P. Franck (1745-1823) and the "phrenology" by F. J. Gall (1745-1823). Under the influence of the great pathologist C. Rokitansky (1804-1878), the tripode of the Vienna neurology - L. Türck (1810-1868), as initiator, Th. v. Meynert (1833-1892) the activator, and H. Obersteiner (1847-1922) as the founder of the Vienna Neurological Institute, presented basic contributions to the morphology and pathology of the nervous system. At the end of the 19(th) and in the early 20(th) century, they were followed by important publications by S. Fred (aphasia), C. Redlich (tabes dorsalis), F. Sträussler (CNS syphilis), A. Spitzer (fiber anatomy of the brain), P. Schilder (diffuse sclerosis), R. Barany (Nobel price for physiology and medicine 1914), J. Wagner v. Jauregg (Nobel price for medicine, 1927), O. Loewi (Nobel Price for Physiology and Medicine together with Sir H. Dale, 1936), A. Schüller (histiocytosis X), C. v. Economo (encephalitis lethargica and cytoarchitectonics of the human cerebral cortex), E. Pollak (Wilson disease), E. Gamper (mesencephalic subject), J. Gerstmann (Gerstmann-Sträussler-Scheinker syndrome and Gerstmann parietal syndrome), H. Hoff with L. Schönbauer (brain tumors and surgery), and others. Major research institutions were the departments of psychiatry I and II at the University of Vienna School of Medicine (foundation 1870), unification 1911, separation into departments of neurology, psychiatry and neuropsychiatry of children and adolescents in 1971), the Obersteiner Institute in Vienna (foundation 1882, separation 1993), the university departments at Graz and Innsbruck, both founded in 1891, and other laboratories, where renouned clinicans and neuroscientists, like O. Marburg, H. Hoff, O. Pötzl, O. Kauders, F. Seitelberger, H. Tschabitscher, K. Weingarten, H. Reisner,W. Birkmayer, H. Petsche, F. Gerstenbrand, H. Bernheimer, H. W. Heiss, H. Lassmann, W. Poewe, L. Deecke, and many of their associates produced important contributions to wide areas of modern neurosciences. Important for the future are the foundation of the Institute of Brain Research at Vienna Medical University and of the Austrian Society of Neurology which will give further impact for the future progress of neuroscience research in Austria and its integration into the international science community.

Academic Medical Centers↗
PubMed2006

Prevalence and impact of cerebrovascular pathology in Alzheimer's disease and parkinsonism.

OBJECTIVE: To study the prevalence and impact of cerebrovascular lesions (CVL) in Alzheimer's disease (AD) and their effects on cognitive impairment. MATERIAL AND METHODS: In study I, the prevalence of vascular lesions in a prospective series of 244 autopsy-proved AD cases (mean age 83.1+/-8.4 years) and 230 age-matched non-demented controls was examined using immunochemistry and current morphological diagnostic criteria. In study II, in 100 consecutive autopsy cases (mean age 84.3+/-9.3 years), the incidence of general and capillary cerebral amyloid angiopathy (CAA, CapCAA) was examined. RESULTS: In study I, AD cases showed significantly more frequent CVL than age-matched controls without differences in the Braak stages, but the severity of CAA was significantly higher in AD brain with associated vascular lesions. In study II, CAA was more frequent in demented than in non-demented patients, but did neither correlate with high-grade AD pathology nor with clinical dementia, whereas CapCAA correlated with both dementia and high Braak stages; the severity of both types of CAA showed only low correlation with each other. CONCLUSIONS: The present data and other studies confirm the importance of CVL in AD and Parkinson's disease without considerable impact on cognitive impairment in progressed stages of AD, and the close association of CapCAA but not of general CAA with clinical dementia and AD pathology.

Age Factors↗
PubMed2004

Lewy body-related alpha-synucleinopathy in the aged human brain.

To clarify the significance of Lewy body (LB)-related alpha-synucleinopathy in aging and various neurodegenerative disorders, its incidence and topographic pattern were examined in 260 brains of elderly patients, including 116 autopsy-proven cases of Alzheimer disease (AD), 71 cases of clinically and autopsy-proven Parkinson disease (PD), 38 of dementia with Lewy bodies (DLB), 8 patients with progressive supranuclear palsy (PSP), one with senile tremor, and 26 age-matched controls without neuropsychiatric disorders. Using immunohistochemistry, alpha-synuclein (AS) positive lesions were assessed semiquantitatively. For technical reasons, the olfactory system was not systematically studied. All PD-brains showed AS-positive lesions in medullary, pontine and mesencephalic nuclei, with involvement of the nucleus basalis (90.1%), limbic cortex (58.9%), cingulate cortex (46%), amygdala, CA 2/3 hippocampal region (36.2%), neocortex (28.8%), and striatum (11%). 88% of clinical PD cases corresponded to LB pathology stages 4-6, 12% to stage 3 according to Braak et al. (2003). 84% of DLB brains were PD stage 5 or 6 and 17% stage 4, without significant differences between DLB with and without neuritic AD pathology, suggesting morphologic similarities betwee these disorders. 6/8 PSP and senile tremor cases, 49.1% of AD and 69% of aged controls were negative. AS-positive lesions in AD showed decreasing incidence from midbrain (24-28%), limbic cortex and amygdala (17-18%), nucleus basalis and medullary nuclei (13-17%), cingulate cortex (12%), CA 2/3 region (8%) to neocortex (2%), without gender differences or relationship to the severity of AD pathology (mean Braak stage 5.1). AD cases with AS positive lesions, particularly those with AS pathology in the amygdala, were older at death than negative ones (86.6 vs 83.3 yrs), but this difference was not statistically significant. 15 AD cases (seven of them with mild PD symptoms) and 3 aged controls without parkinsonian signs but LB pathology stages 3 (n=5) and 4 (n=13) were considered "incidental LB disease". 16 AD brains without parkinsonian symptoms had AS positive lesions in various areas without medullary involvement, suggesting deviation from the proposed stereotypic expansion pattern. Located AS-pathology in the midbrain and limbic cortex was seen in 31% of asymptomatic aged controls. These data 1. largely confirm Braak's staging of LB-pathology in PD; 2. suggest morphologic and pathogenic relations between PD (brainstem type) and DLB with and without coexistent AD pathology; 3. the occurrence of LB-related alpha-synucleinopathy in about 50% of AD brains and about 30% of aged controls. However, the basic mechanisms of LB-related AS-pathology and their pathogenic and clinical relevance in aged brain and neurodegenerative disorders await further elucidation.

Aged↗
PubMed2004

Pathology and pathophysiology of vascular cognitive impairment. A critical update.

The prevalence, morphology, and pathogenesis of vascular dementia (VaD), recently termed vascular cognitive impairment (VCI), and of mixed dementia (Alzheimer disease associated with vascular encephalopathy) are a matter of discussion and clinical diagnostic criteria for these disorders slow low sensitivity and variable specificity. In Western memory clinic-based series, VaD/VCI is suggested in 8-10% of cognitively impaired elderly subjects. Its prevalence in autopsy series ranges from 0.03% to 58% with reasonable values of 4-10%. It has been related to focal, multifocal or diffuse cortical and/or subcortical microinfarcts and lacunes often affecting strategically important brain areas (thalamus, frontobasal and/or limbic systems), hemispheric white matter lesions and, less often, large brain infarcts. They result from systemic, cardiac or local large or small vessel disease. The pathogenesis of cerebrovascular lesions is multifactorial and their pathophysiology affects neuronal systems involved in cognition, memory, and behavior. Vascular pathology often coexists with Alzheimer disease (AD) and other dementing disorders; 25-60% of dementia cases show both AD and vascular lesions. The lesion patterns in ''pure'' VCI with predominant multiple small (subcortical) lesions related to arteriosclerosis and microangiopathies and in mixed dementia (AD associated with vascular encephalopathy), more often showing large infarcts, suggest different pathogenesis of both types of lesions. Due to the high variability of cerebrovascular pathology and its causative factors no validated neuropathological criteria exist for VCI and mixed dementia. In very old subjects selective hippocampal sclerosis may be associated with multiple other vascular pathologies. Minor cerebrovascular lesions, except for severe amyloid angiopathy, appear not essential for cognitive decline in full-blown AD, while both mild AD-type pathology and small vessel disease may interact synergistically in ''unmasking'' or promoting dementia. AD pathology is significantly less severe in the presence of cerebrovascular lesions. Further studies are needed to validate diagnostic criteria for VaD/VCI and to clarify the impact of vascular lesions on cognitive impairment as a basis for more precise clinical diagnosis, early prevention and management.

Alzheimer Disease↗
PubMed2003

Immunoreactivities of amyloid beta peptide((1-42)) and total tau protein in lumbar cerebrospinal fluid of patients with normal pressure hydrocephalus.

Immunoreactivities of amyloid beta peptide((1-42)) (Abeta42-IR) and total tau protein (TTIR) were measured in lumbar cerebrospinal fluid of 48 patients (12 patients in each group) with normal pressure hydrocephalus (NPH), vascular dementia (VD), Alzheimer's disease (AD), Parkinson's disease without dementia (PD) and 24 controls (CON) using sensitive and specific enzyme immunoassays. TTIR in NPH was not significantly changed compared with VD, PD and CON, while NPH-Abeta42-IR was significantly decreased compared with PD and CON. In AD, significant increases of TTIR and significant decreases of Abeta42-IR were found. Using a TTIR by Abeta42 plot, all NPH, PD, and CON samples were within the non-AD plot region. 92% of AD and VD samples were within the AD and non-AD area, respectively. We conclude that combined measurement of Abeta42-IR and TTIR contributes to the differential diagnosis of NPH vs. AD and of AD vs. VD, respectively.

Adult↗
PubMed2003

General aspects of neurodegeneration.

Neurodegenerative diseases are morphologically featured by progressive cell loss in specific vulnerable neuronal populations of the central nervous system, often associated with cytoskeletal protein aggregates forming intracytoplasmic and/or intranuclear inclusions in neurons and/or glial cells. Most neurodegenerative disorders are now classified either according to the hitherto known genetic mechanisms or to the major components of their cellular protein inclusions. The major basic processes inducing neurodegeneration are considered multifactorial ones caused by genetic, environmental, and endogenous factors. They include abnormal protein dynamics with defective protein degradation and aggregation, many of them related to the ubiquitin-proteasomal system, oxidative stress and free radical formation, impaired bioenergetics and mitochondrial dysfunctions, and "neuroinflammatory" processes. These mechanisms that are usually interrelated in complex vitious circles finally leading to programmed cell death cascades are briefly discussed with reference to their pathogenetic role in many, albeit diverse neurodegenerative diseases, like Alzheimer disease, synucleinopathies, tauopathies, and polyglutamine disorders. The impact of protein inclusions on cell dysfunction, activation or prevention of cell death cascades are discussed, but the molecular basis for the underlying disease mechanisms remains to be elucidated.

Animals↗
PubMed2003

Rett Syndrome -- an update.

Rett syndrome is a progressive, usually sporadic and rarely familial, disabling neurodevelopmental disorder with onset in early childhood presenting clinically with mental retardation, behavioral changes, late movement disturbances, loss of speech and hand skills, ataxia, apraxia, irregular breathing with hyperventilation while awake, and frequent seizures. It occurs almost exclusively in females with an estimated prevalence of 1 in 10-22000 births and is considered a manifestation of defective brain maturation caused by dominant mutation of the MeCP2 gene encoding the transcriptional repressor methyl-CpG-binding protein 2 related to the Xq28 locus. Although many different mutations of this protein are being studied in humans and in mice, the molecular pathogenesis of this disorder remains unclear. Electroencephalography is abnormal in the final stages of the syndrome. Neuroimaging showing brain atrophy may be required for differential diagnosis that includes neurodegenerative and metabolic disorders. Neuropathology shows decreased brain growth and reduced size of individual neurons, with thinned dendrites in some cortical layers and abnormalities in substantia nigra (decreased neuromelanin content), suggestive of deficient synaptogenic development, probably starting before birth. Neurometabolic changes include reduced levels of dopamine, serotonin, noradrenalin, choline acetyltransferase (ChAT), nerve growth factors, endorphines, glutamate, and other amino acids and their receptor levels in brain. Current treatment includes symptomatic, anticonvulsive and physiotherapy.

Brain↗
PubMed2003

Prevalence of vascular lesions in dementia with Lewy bodies. A postmortem study.

The frequency of vascular lesions in dementia with Lewy bodies (DLB) has been suggested to be less common than for Parkinson disease (PD), but exact data on the relationship between DLB and stroke are not available. 387 consecutive cases of autopsy-proven Lewy body disease - 291 cases of idiopathic PD (Lewy body disease of brainstem type) and 96 cases of DLB - and 390 age-matched controls were compared using current routine stains and immunohistological methods. The frequency of cerebrovascular lesions of various intensity (lacunes, amyloid angiopathy, old ischemic infarcts and hemorrhages) was lower in DLB than in both PD and controls (34.4% vs. 36.7% and 33.3%) (p > 0.03). While acute ischemic strokes and hemorrhages were rarely present in both PD and controls (4.1 vs. 3.3%), no such lesions were observed in DLB. At variance to previous findings in autopsy-proven PD and Alzheimer disease (AD), these data suggest a protective effect against stroke and no greater susceptibility to death from stroke in the DLB population studied, but the reasons remain unclear. On the other hand, like in PD and AD, cognitive impairment in DLB appears to be independent from coexisting vascular pathology and is mainly related to neuritic Alzheimer pathology.

Aged↗
PubMed2002

Vascular-ischemic dementia: an update.

Both the clinical criteria and morphologic substrates of dementia resulting from cerebrovascular disease and its relation to Alzheimer disease and other age-related brain changes are controversial. In clinical and autopsy studies in the Western world the prevalence of vascular-ischemic dementia (VID) is around 7-10%, while vascular cognitive impairment without dementia is much more frequent and the risk of poststroke dementia is increased in patients with prestroke cognitive decline. In contrast to previous suggestions that VID was largely the result of large hemispheral infarcts, according to recent studies, it is most commonly associated with widespread small ischemic or vascular lesions (microinfarcts, lacunes) throughout the CNS with predominant subcortical lesions in the basal ganglia and white matter or in strategically important brain regions (thalamus, hippocampus). The lesion pattern of rare "pure" VID, which is related to arteriolosclerotic and hypertensive microangiopathy, differs from that in mixed type dementia (Alzheimer disease and cerebrovascular lesions) that more often shows larger hemispheral infarcts. Another form of VID that is not infrequent in very old subjects is hippocampal sclerosis, a selective damage to the hippocampus that is often accompanied by multiple other cerebrovascular lesions. Both, mild Alzheimer type pathology and small vessel disease-associated subcortical vascular pathology appear to be common and may interact in causing cognitive decline, but the impact of cerebrovascular lesions on cognitive impairment and dementia needs to be further elucidated.

Aged↗
PubMed2002

Recent developments in the pathology of Parkinson's disease.

Parkinson's disease (PD) is morphologically characterized by progressive loss of neurons in the substantia nigra pars compacta (SNpc) and other subcortical nuclei associated with intracytoplasmic Lewy bodies and dystrophic (Lewy) neurites mainly in subcortical nuclei and hippocampus und, less frequently in cerebral cortex. SN cell loss is significantly related to striatal dopamine (DA) deficiency as well as to both the duration and clinical severity of disease, The two major clinical subtypes of PD show different morphologic lesion patterns: the akinetic-rigid form has more severe cell loss in the ventrolateral part of SN with negative correlation to DA loss in the posterior putamen, and motor symptoms related to overacitivty of the GABAergic "indirect" motor loop, which causes inhibition of the glutamatergic thalamocortical pathway and reduced cortical activation. The tremor-dominant type shows more severe cell loss in the medial SNpc and retrorubal field A 8, which project to the matrix of the dorsolateral striatum and ventromedial thalamus, thus causing hyperactivity of thalamomotor and cerebellar projections. These and experimental data suggesting different pathophysiological mechanisms for the major clinical subtypes of PD may have important therapeutic implications. Lewy bodies, the morphologic markers of PD, are composed of hyperphosphorylated neurofilament proteins, lipids, redox-active iron, ubiquitin, and alpha-synuclein, showing a continuous accumulation in the periphery and of ubiquitin in the central core. Alpha-synuclein, is usually unfolded in alpha-helical form. By gene mutation, environmental stress or other factors it can be transformed to beta-folding which is sensible to self-aggregation in filamentous fibrils and formation of insoluble intracellular inclusions that may lead to functional disturbances and, finally, to death of involved neurons. While experimental and tissue culture studies suggest that apoptosis, a genetically determined form of programmed cell death, represents the most common pathway in neurodegeneration, DNA fragmentation, overexpression of proapoptotic proteins and activated caspase-3, the effector enzyme of the terminal apopoptic cascade, have only extremely rarely been detected in SN of PD brains. This is in accordance with the rapid course of apoptotis and the extremely slow progression of the neurodegenerative process in PD. The biological role of Lewy bodies and other intracellular inclusions, the mechanisms of the intracellular aggregation of insoluble protein deposits, and their implication for cellular dysfunction resulting in neurodegeneration and cell demise are still unresolved. Further elucidation of the basic molecular mechanisms of cytoskeletal lesions will provide better insight into the pathogenesis of neurodegeneration in PD and related disorders.

Brain↗