Search PubMed⌕ Search

Biomedical subjects

K A Jellinger

Publications and source records attributed to K A Jellinger.

At least 73 records · Page 4Linked to original sources
PubMed1998

The neuropathological diagnosis of Alzheimer disease.

The unequivocal diagnosis of Alzheimer disease (AD) rests on histopathological evidence at brain autopsy or biopsy. Although the histological features of AD are well known, defining criteria for the morphological diagnosis of AD is difficult due to the phenotypical heterogeneity of the disease, absence of specific markers, and overlap of AD pathology with that observed in non-demented elderly individuals. This gray zone between normal to pathological aging and full-fledged AD represents an important diagnostic problem and should be overcome by better standardized criteria that will allow to minimize interrater and interlaboratory variability in the diagnosis of AD. Current criteria for the neuropathological diagnosis of AD are based on age-related (semi)quantitative assessment of "senile" plaques (NIA criteria), neuritic plaques (CERAD), plaques and neurofibrillary tangles in neocortex and hippocampus (Tierney et al., 1988), and staging of hierarchic spreading of neuritic AD changes in particular, neurofibrillary tangles (Braak and Braak, 1991). All these algorithms have some weaknesses and do not recognize the various subtypes of AD. Multivariant analysis of an autopsy series of elderly subjects revealed significant correlations between psychostatus assessed by the Mini-Mental State and both the CERAD criteria and Braak staging. Although the role of plaques and tangles in the pathogenesis of AD and their relationship to both neuronal loss and dementia remain to be elucidated, clinicopathological studies have shown that both lesions, if present in sufficient numbers, particularly in the neocortex, are considered the best correlates for AD related dementia. Recent consensus recommendations of the NIA- and Reagan Institute Working Group for the morphological diagnosis of AD consider AD as a heterogenous clinicopathological entity. After exclusion of other causes of dementia, the likelihood that AD accounts for dementia is considered high, intermediate or low according to the frequency of neuritic AD lesions with regard to both the CERAD criteria and Braak staging. The evaluation of small autopsy series according to these criteria demonstrated their easy and rapid application in AD and non-demented subjects, with much less reliability for other dementing disorders.

Aged↗
PubMed1998

Neuropathology of Alzheimer's disease: a critical update.

The unequivocal diagnosis of Alzheimer's disease (AD) rests on histopathological evidence at brain autopsy or biopsy. The morphology of AD includes cerebral atrophy, deposition of beta A4 amyloid (A beta) (senile plaques and amyloid angiopathy), neuritic changes (neuritic plaques, neurofibrillary tangles (NFT) and neuropil threads) with formation of paired helical filaments (PHF) containing polymerized hyperphosphorylated tau protein triplet, causing disruption of the neuronal cytoskeleton with loss of synapses and neurons, with altered cortico-cortical connectivity, leading to disconnection of the cerebral cortex. Defining criteria for the morphologic diagnosis of AD is difficult due to the phenotypic heterogeneity of the disease, the absence of specific markers, and overlap of AD morphology with that observed in non-demented elderly individuals. This gray zone between normal to pathologic aging and full-fledged AD represents an important diagnostic problem and should be overcome by better standardized criteria that will allow to minimize interrater and interlaboratory variability in the diagnosis of AD. Current criteria for the morphologic diagnosis of AD are based on (semi)quantitative assessment of diffuse and neuritic plaques (NIA), exclusively neuritic plaques (CERAD), plaques and NFT in neocortex and hippocampus (Tierney et al., 1988), and staging of hierarchic spreading of neuritic AD changes (Braak and Braak, 1991); all of them have weaknesses and need to be revalidated. Multivariant analysis of an autopsy series of elderly subjects revealed significant correlations between psychostatus and both the CERAD criteria and Braak staging. Recent recommendations of the NIA-Reagan Institute for the morphologic diagnosis of AD are presented. Although the role of plaques and NFT in the pathogenesis of AD remains undetermined, clinicopathological correlative studies have shown that both lesions, if present in sufficient numbers, particularly in the neocortex, are considered the best morphological signposts for AD. Recent studies on neuron death in AD that, at least in part, appears different from classical apoptosis and may precede the symptomatic stage of AD, have shown varying results indicating only indirect relationship between DNA fragmentation and both A beta deposition and NFTs. Both these AD-typical markers appear to increase the risk of cells to degenerate, but are not the sole responsibles of the degenerative process in AD, the basic mechanisms of which remain to be elucidated.

Aged↗
PubMed1998

Alzheimer-type lesions in Huntington's disease.

Cognitive changes in Huntington's disease (HD) are variously related to diffuse cortical atrophy with neuron loss and dystrophic neurites leading to disruption of striato-frontal or limbic circuitries, while recent studies suggest an increasing prevalence of Alzheimer-like lesions in HD brain. A comparative morphological study of 27 autopsy cases of HD (age 34 to 75 years) and of 26 age- and sex-matched non-demented controls was performed. Absence of Alzheimer-type lesions was seen in 33% of HD brains (mean age 49 years); 48% showed early non-neuritic tau pathology in limbic areas (Braak stages I and II) without amyloid deposits occurring as early as age 34 years (mean age 54 years), while Braak stages II and III with amyloid plaques were present in 19%, the youngest such HD patient being 42 years (mean age 54 years). In controls, similar tau pathology changes with later onset (age 45 years) and occurrence of amyloid plaques in 26%--all aged over 60 years--were observed. No probable or definite cases of Alzheimer disease (AD) according to CERAD criteria were seen in both cohorts. Those data confirm previous studies on the rare coexistence of HD and AD, although initial stages of Alzheimer-like lesions develop rather early in HD patients, but obviously show less rapid progress even in advanced age. The reasons for the early onset but mild progress of Alzheimer-like lesions in HD and their contribution to cognitive decline await further elucidation.

Adult↗
PubMed1998

Senile dementia with tangles (tangle predominant form of senile dementia).

Senile dementia with tangles is a sporadic subset of very late onset dementia with preponderance in females over age 80 years. Neuropathology shows diffuse cerebral atrophy with neurofibrillary tangles, often ghost tangles, and neuropil threads almost limited to limbic areas (transentorhinal, entorhinal area, hippocampuS--not exclusively sector CA 1--and amygdala) with only rare and mild involvement of the neocortex, basal ganglia and brainstem (except nucleus basalis and locus ceruleus), absence of neuritic plaques and absence or scarcety of amyloid deposits. This pattern of fibrillary pathology corresponds to Braak stages III and IV or the "limbic" type of Alzheimer disease that is considered the main form in the oldest-old but escapes the current criteria for the morphologic diagnosis of Alzheimer disease. It is distinct from other tau- or tangle-pathology related conditions, e.g. progressive supranuclear palsy, autosomal dominant dementia with tangles, and diffuse tangles with calcification. Very low prevalence of ApoE e4 allele (0.03-0.11%) and higher frequency of ApoE e3 and/or e2 suggest a lack of promoting effect of e4 and a possible protecting effect of e2/3 on amyloidogenesis. Senile dementia with tangles is suggested to be a variant of Alzheimer disease occurring in the oldest-old, but its nosological position within aging disorders of the brain is still controversy.

Alleles↗
PubMed1998

Dementia with grains (argyrophilic grain disease).

Dementia with grains, also referred to as argyrophilic grain disease, is a morphological condition in elderly individuals histologically characterised by the widespread occurrence of minute, spindle or comma-shaped argyrophilic, tau-immunoreactive structures distinct from neuropil threads that are predominantly located in the hippocampus and related limbic areas including the amygdala. They are suggested to arise mainly in dendrites of neurons showing accumulation of hyperphosphorylated tau proteins (pretangle stage) but not necessarily forming paired helical filaments. Argyrophilic grains are associated with argyrophilic, tau-positive oligodendroglial inclusions ("coiled bodies") in the white matter, while astroglia are not affected. Argyrophilic grain disease is considered to be a progressive disorder that may or may not be associated with dementia, the grains occasionally being the only morphologic substrates of cognitive decline. They often occur in combination with neuritic Alzheimer-type lesions (many corresponding to "limbic" Braak stages III and IV) or other neurodegenerative disorders, such as progressive supranuclear palsy, corticobasal degeneration, or Pick's disease. The prevalence and pathogenesis of this condition, its clinicopathologic correlations and nosological position among tau-pathology related disorders await further elucidation.

Brain↗
PubMed1998

Neuropathology of movement disorders.

This article reviews the cytoskeletal abnormalities, morphologic lesion patterns, and resulting pathophysiology of the most frequent neurodegenerative movement disorders caused by dysfunction of the basal ganglia and related neuronal loops. The following topics are discussed: Among the akinetic-rigid Lewy body disorders is idiopathic Parkinson's disease, which reveals specific lesion patterns of pathophysiologic and therapeutic relevance. Dementia with Lewy bodies characterized by cortical Lewy bodies appears intermediate between Parkinson's and Alzheimer's diseases. Tau pathologic disorders may show some clinical and morphologic overlap. Multiple system atrophy has ubiquitous oligodendroglial inclusions as a cytopathologic hallmark. Secondary parkinsonism includes drug-related, toxic, and other symptomatic disorders. Hyperkinetic disorders include CAG-related inherited diseases, showing specific genetic defects and morphologic lesions. Dystonia syndromes show inconsistent pathologic findings, and myoclonus may be related to a variety of disorders. Consensus data on clinical and neuropathologic criteria already existing for some disorders, together with molecular genetic and biochemical data will provide further insight into the complex pathophysiology and pathogenesis of movement disorders.

Humans↗
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↗