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K A Jellinger

Publications and source records attributed to K A Jellinger.

At least 91 records · Page 5Linked to original sources
PubMed1996

Structural basis of dementia in neurodegenerative disorders.

Progressive dementia syndromes in adults are caused by a number of conditions associated with different structural lesions of the brain. In most clinical and autopsy series, senile dementia of the Alzheimer type is the most common cause of mental decline in the elderly accounting for up to 90%, whereas degenerative non-Alzheimer dementias range from 7 to 30% (mean 8-10%). They include a variety of disorders featured morphologically by neuron and synapse loss and gliosis, often associated with cytopathological changes involving specific cortical and subcortical circuits. These neuronal/glial inclusions and neuritic alterations show characteristic immunoreactions and ultrastructure indicating cytoskeletal mismetabolism. They are important diagnostic sign posts that, in addition to the distribution pattern of degenerative changes, indicate specific vulnerability of neuronal populations, but their pathogenic role and contribution to mental decline are still poorly understood. In some degenerative disorders no such cytopathological hallmarks have been observed; a small number is genetically determined. While in Alzheimer's disease (AD) mental decline is mainly related to synaptic and neuritic pathologies, other degenerative disorders show variable substrates of dementia involving different cortical and/or subcortical circuits which may or may not be superimposed by cortical Alzheimer lesions. In most demented patients with Lewy body disorders (Parkinson's disease, Lewy body dementia), they show similar distribution as in AD, while in Progressive Supranuclear Palsy (PSP), mainly prefrontal areas are involved. Lobar atrophies, increasingly apparent as causes of dementia, show fronto-temporal cortical neuron loss, spongiosis and gliosis with or without neuronal inclusions (Pick bodies) and ballooned cells, while dementing motor neuron disease and multisystem atrophies reveal ubiquitinated neuronal and oligodendroglial inclusions. There are overlaps or suggested relationships between some neurodegenerative disorders, e.g. between corticobasal degeneration, PSP and Pick's atrophy. In many of these disorders with involvement of the basal ganglia, degeneration of striatofrontal and hippocampo-cortical loops are important factors of mental decline which may be associated with isocortical neuronal degeneration and synapse loss or are superimposed by cortical AD pathology.

Aged↗
PubMed1996

Tau protein and apolipoprotein E in CSF diagnostics of Alzheimer's disease: impact on non Alzheimer's dementia?

Tau protein and apolipoprotein E are suggested to be biochemically related to neurofibrillary tangles and senile plaques in Alzheimer's disease (AD) brains. They can be detected as immunoreactive material (total tau immunoreactivity [TTIR] and apolipoprotein E-immunoreactivity [ApoEIR]) in the cerebrospinal fluid (CSF). TTIR and ApoE-IR have been measured in ex vivo lumbar and post mortem ventricular CSF in AD, other neurological diseases without cognitive impairment, elderly depressive patients, and young and elderly controls. In lumbar CSF, there was a highly significant increase of TTIR and a minor, insignificant decrease of ApoE-IR in CSF of AD patients. The latter result was also found in ventricular CSF, whereas TTIR showed no significant difference between groups in the rostral CSF compartment. As depressive periods in the elderly may mimick a dementing process, these findings contribute to the differential diagnosis of these disorders by showing a different neurobiochemical CSF profile. Work in progress will include a variety of non-Alzheimer's dementias and possibly will further increase the value of CSF investigation in neurodegenerative disorders.

Adult↗
PubMed1996

Progressive supranuclear palsy: a clinicopathological study of 21 cases.

The symptoms and signs used to diagnose progressive supranuclear palsy (PSP) should be easily identifiable by neuropathologists and neurologists as well as by movement disorder experts. The presence, at the time of death, of symptoms and signs that are used in published clinical criteria for the diagnosis of this disorder was searched for in 21 pathologically confirmed typical PSP cases. The following items, present in at least 80% of pathologically confirmed cases, can be considered as the most accurate clinical data for the diagnosis of PSP: non-familial parkinsonism, not improved by L-dopa therapy, with vertical voluntary gaze palsy; postural instability and falls; pseudobulbar palsy and dementia with frontal lobe-like syndrome; and a progressive course of less than 10 years. The definite diagnosis of PSP must be clinicopathological, and these minimal clinical data may be used for this purpose.

Adult↗
PubMed1996

Intra vitam lumbar cerebrospinal fluid and serum and postmortem ventricular immunoreactive apolipoprotein E in patients with Alzheimer's disease.

Using a specific enzyme linked immunosorbent assay (ELISA) method, total apolipoprotein E immunoreactivity (tApoE-IR) was measured in premortem lumbar CSF and serum of patients with "probable" Alzheimer's disease and in postmortem ventricular CSF of patients with Alzheimer's disease confirmed by necropsy. Concentrations were compared with those from patients with other neurological diseases and controls. The mean serum:lumbar CSF ratio of ApoE-IR was 15.9 suggesting that the main portion of lumbar ApoE-IR is synthesised intrathecally. No significant differences in ApoE-IR between patients with Alzheimer's disease and the other groups were detected in either CSF compartment. In lumbar CSF, there was no correlation between ApoE-IR of patients with Alzheimer's disease and their mini mental state scores. These results suggest that the diagnostic value of ApoE-IR measurements in CSF of patients with Alzheimer's disease as a single determination is less than that of other markers, in particular tau protein. On the other hand, ApoE determinations could be useful as part of a neurochemical profile of Alzheimer's disease.

Aged↗
PubMed1996

AD neuropathology.

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Alzheimer Disease↗
PubMed1996

Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop.

Recent neuropathologic autopsy studies found that 15 to 25% of elderly demented patients have Lewy bodies (LB) in their brainstem and cortex, and in hospital series this may constitute the most common pathologic subgroup after pure Alzheimer's disease (AD). The Consortium on Dementia with Lewy bodies met to establish consensus guidelines for the clinical diagnosis of dementia with Lewy bodies (DLB) and to establish a common framework for the assessment and characterization of pathologic lesions at autopsy. The importance of accurate antemortem diagnosis of DLB includes a characteristic and often rapidly progressive clinical syndrome, a need for particular caution with neuroleptic medication, and the possibility that DLB patients may be particularly responsive to cholinesterase inhibitors. We identified progressive disabling mental impairment progressing to dementia as the central feature of DLB. Attentional impairments and disproportionate problem solving and visuospatial difficulties are often early and prominent. Fluctuation in cognitive function, persistent well-formed visual hallucinations, and spontaneous motor features of parkinsonism are core features with diagnostic significance in discriminating DLB from AD and other dementias. Appropriate clinical methods for eliciting these key symptoms are described. Brainstem or cortical LB are the only features considered essential for a pathologic diagnosis of DLB, although Lewy-related neurites, Alzheimer pathology, and spongiform change may also be seen. We identified optimal staining methods for each of these and devised a protocol for the evaluation of cortical LB frequency based on a brain sampling procedure consistent with CERAD. This allows cases to be classified into brainstem predominant, limbic (transitional), and neocortical subtypes, using a simple scoring system based on the relative distribution of semiquantitative LB counts. Alzheimer pathology is also frequently present in DLB, usually as diffuse or neuritic plaques, neocortical neurofibrillary tangles being much less common. The precise nosological relationship between DLB and AD remains uncertain, as does that between DLB and patients with Parkinson's disease who subsequently develop neuropsychiatric features. Finally, we recommend procedures for the selective sampling and storage of frozen tissue for a variety of neurochemical assays, which together with developments in molecular genetics, should assist future refinements of diagnosis and classification.

Dementia↗
PubMed1995

Primary central nervous system lymphomas--new pathological developments.

Primary central nervous system lymphomas (PCNSL) show increased incidence both in immunocompromised high-risk groups and in the general population. They are extranodal diffuse non-Hodgkin's lymphomas with a morphology similar to systemic lymphomas, but differ in their biological and molecular behaviour. The majority are large B-cell variants of high-grade malignancy; low-grade subtypes and T-cell lymphomas are rare; up to 50% remain unclassified according to the New Working Formulation and updated Kiel classification. Monoclonality of immunoglobulin receptor gene rearrangement can be diagnostically useful. The pathogenesis of PCNSL is obscure. Epstein-Barr virus (EBV) genome/proteins expression in two-thirds of HIV-related PCNSL but only in 15% of those in immunocompetent patients suggest different EBV latency stages in both types; human herpesvirus type 6 does not appear to play a pathogenic role. Comparison of expression patterns of integrin chains and adhesion molecules are very similar for PCNSL and nodal lymphomas suggesting that they are not selective mediators of lymphoma cell homing to the brain. In HIV-negative PCNSL they appear not to be influenced by EBV. Studies of protooncogenes (bcl-1 and bcl-2 genes) revealed no rearrangement in PCNSL, suggesting that they are not involved in the pathogenesis of PCNSL that probably do not differ cytogenetically from nodal B-cell lymphomas. Since most of the currently known molecular parameters are probably not the primary pathogenic events, the molecular genetics and pathogenesis of PCNSL are still to be elucidated.

Cell Adhesion Molecules↗