PubMed Health⌕ Search

Biomedical subjects

K A Jellinger

Publications and source records attributed to K A Jellinger.

At least 19 recordsLinked to original sources
PubMed1997

Mechanisms of cell death in Alzheimer's disease.

The etiology of Alzheimer's disease (AD) as well as its exact pathogenesis are unknown. Eventhough the deposition of beta A4 and the formation of neurofibrillary tangles represent impressive morphological hallmarks of the disease, several lines of evidence suggest that both lesions are not sufficient as causes of the neurodegenerative process. On the other hand, in vitro studies have shown that beta A4 is neurotoxic and is able to induce apoptotic cell death in neuronal cell cultures. Cells dying by apoptosis (programmed cell death) can be visualized in the tissue with a molecular biologic technique detecting fragmented nuclear DNA. Using this method, we have detected 50 x more neurons and 25 x more glial cells with nuclear DNA fragmentation in the brains of patients with AD than in non-demented controls. In contrast to previous studies, most of these cells did not reveal the characteristic morphological hallmarks of apoptosis. Most dying cells were not located within amyloid deposits and most dying cells did not bear a tangle. On the other hand, being in physical contact with an amyloid deposit increased the risk of a cell to dye by factor 5.7 and carrying a neurofibrillary tangle imposed a 3 times higher risk compared to unaffected nerve cells. Taken together, these data indicate that nerve cell death in AD occurs via a mechanism of programmed cell death different from classical apoptosis. Eventhough plaques and tangles increase the risk of cells to degenerate, both lesions are not the sole responsibles of the degenerative process, suggesting the existence of other factors that trigger the initiation of the cell death program in AD.

Aged↗
PubMed1997

Morphological substrates of dementia in parkinsonism. A critical update.

Dementia in parkinsonism is caused by a variety of central nervous system (CNS) lesions, of which the molecular and pathogenic causes are poorly understood but probably include: 1. Degeneration of subcortical ascending systems with neuronal losses in dopaminergic, noradrenergic, serotonergic, cholinergic or multiple systems including the amygdyloid nucleus; 2. limbic and/or cortical Alzheimer and/or Lewy body pathologies, with loss of synapses and neurons, and 3. a combination of these lesions or additional CNS pathologies. In general, degeneration of subcortical neuronal networks appears insufficient to induce severe mental decline although, occasionally, cognitive impairment occurs without apparent cortical lesions. On the other hand, neuritic cortical Alzheimer change showing similar or differential distribution compared to Alzheimer's disease (AD) displays a significant linear correlation with dementia in Parkinsonism. Plaques can be associated with cortical Lewy bodies and, the contribution of each to dementing processes remains unresolved. In a consecutive autopsy series of 610 patients with parkinsonism, the total prevalence of retrospectively assessed dementia was 34.6%. In Parkinson's disease (PD) of the Lewy body type, it was 30.2%, mostly associated with other brain lesions, mainly AD, while only 3.5% of "pure" PD without additional brain pathologies were demented. There was no significant difference in age and duration of illness between demented and non-demented PD patients. Secondary parkinsonian syndromes showed a higher incidence of dementia (56.3%), again with predominant Alzheimer pathology which was present in 73% of the total of demented parkinsonian patients and in almost 82% of the demented PD cases in this series. The specific contribution of cortical and subcortical lesions to mental impairment in parkinsonism, their relationship to AD, and an etiology await further elucidation.

Aged↗
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.

Explore the source record for details and available documents.

Alzheimer Disease↗