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E N Jansen Steur

Publications and source records attributed to E N Jansen Steur.

At least 19 recordsLinked to original sources
PubMed2006

Age-related microvascular degeneration in the human cerebral periventricular white matter.

Clinical studies have identified white matter (WM) lesions as hyperintensive regions in the MRI images of elderly patients. Since a cerebrovascular origin was attributed to such lesions, the present analysis set out to define the microvascular histopathologic changes in the periventricular WM in the aged. Post-mortem samples of the frontal, parietal, and occipital periventricular WM of 40-90-year-old subjects were prepared for quantitative light and electron microscopy. Light microscopic examination revealed microvascular fibrohyalinosis as the most common type of microvascular damage in the elderly. Ultrastructural analysis identified the microvascular thickening as collagen deposits affecting the basement membrane. The vascular density did not correlate with the age. The basement membrane pathology significantly increased, while the number of intact microvessels gradually decreased, with advancing age in the frontal and occipital WM. Finally, peripheral atherosclerosis coincided with massive microvascular fibrosis, particularly in the frontal WM. Our results demonstrate an age-related microvascular degeneration in the periventricular WM, which may contribute to the development of WM lesions by hindering a sufficient supply of nutrients to the affected WM sites. Furthermore, the data accord with previous observations identifying the frontal lobe as the site at which WM vulnerability is most pronounced. Finally, atherosclerosis in large, peripheral vessels is considered to be a predictive marker of microvascular pathology in the WM.

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PubMed2000

Quantitative assessment of nicotinic acetylcholine receptor proteins in the cerebral cortex of Alzheimer patients.

Cholinergic transmission has for long been known to be one of the most severely affected systems in Alzheimer's disease (AD), resulting clinically in massive cognitive deficits. The molecular basis of this dysfunction--on both the pre- and the postsynaptic sites--is still a matter of ongoing investigations. Here, we report on the quantitative assessment of nicotinic acetylcholine receptor isoform expression in AD vs. control cortices. For both subunit proteins assessed, the alpha4 and the alpha7 isoform, highly significant decreases in diseased vs. normal cortices were observed. Both alpha4 and alpha7 subunits are known to be important constituents in hetero- (alpha4beta2) and homooligomeric (alpha7) receptor subtypes. Their decreased expression may contribute to the decreased nicotinic binding known to be accompanied by AD and severe cognitive deficits. The quantitative assessment of nicotinic acetylcholine receptor expression will help to determine those subunits suited as targets for pharmacological stimulation.

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PubMed2000

Cellular expression of alpha7 nicotinic acetylcholine receptor protein in the temporal cortex in Alzheimer's and Parkinson's disease--a stereological approach.

Cognitive deficits in Alzheimer's and Parkinson's disease are closely related to disturbed cholinergic transmission. The decrease of nicotinic acetylcholine receptor protein has been assessed by Western blotting and immunohistochemistry. Stereology, however, has not been used to assess numbers of receptor-expressing human cerebrocortical neurons. Our approach applies a combination of alpha7 subunit-immunohistochemistry with a stereological technique using defined stretches of pial surface as reference standard. The number of alpha7 subunit protein-expressing neurons in the Alzheimer temporal cortices amounted to approximately half of that of controls while numbers in Parkinson patients lay in between. No differences in the total number of neurons were seen. These results corroborate nonstereological studies on Alzheimer cortices and for the first time show a similar decrease in receptor expression in Parkinson's disease. They provide evidence that not only Alzheimer dementia but also cognitive deficits in Parkinson's disease may be related to decreased nicotinic receptor expression.

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PubMed2000

Pathological features of cerebral cortical capillaries are doubled in Alzheimer's disease and Parkinson's disease.

Cerebral capillaries represent a major interface between the general circulation and the central nervous system and are responsible for sufficient and selective nutrient transport to the brain. Structural damage or dysfunctioning carrier systems of such an active barrier leads to compromised nutrient trafficking. Subsequently, a decreased nutrient availability in the neural tissue may contribute to hampered neuronal metabolism, hence to behavioral and cognitive functional deficiencies. Here we focus on the ultrastructural abnormalities of cerebral microvessels in Alzheimer's disease (AD: n = 5) and Parkinson's disease (PD; n = 10). The capillary microanatomy in samples from the cingulate cortex was investigated by electron microscopy and severe damage to the vessel walls was observed. Characteristic pathological changes including capillary basement membrane thickening and collagen accumulation in the basement membrane were enhanced in both AD and PD. The incidence of capillaries with basement membrane deposits was two times higher in AD and PD than in age-matched controls. Degenerative pericytes in all groups appeared at a similar frequency. The data indicate that basement membrane deposits, as opposed to pericytic degeneration, represent an important pathological feature of AD and PD and suggest that capillary dysfunction may play a causal role in the development of these two major neurodegenerative diseases.

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PubMed2000

Activated microglial cells and complement factors are unrelated to cortical Lewy bodies.

Inflammatory mechanisms have been demonstrated in Alzheimer's disease (AD) but their presence in other neurodegenerative disorders is not well documented. Complement factors and activated microglia have been reported in the substantia nigra of Parkinson's disease (PD). In the present study we investigated the cingulate gyrus of 25 autopsied patients with clinically and neuropathologically well-documented PD, with or without dementia, for the presence of (activated) microglial cells and their relation with Lewy body (LB)-bearing neurons. In addition, we studied the presence of complement factors in LBs. Of the 25 patient, 15 were clinically demented, fulfilling criteria for dementia with LBs (DLB); 7 also fulfilled CERAD morphological criteria for probable or definite Alzheimer type of dementia. Microglia clustering was seen around congophilic plaques with or without tau pathology. Microglial cells were not associated with LB-bearing neurons or noncongophilic plaques. The cortex of DLB patients without AD plaques did not show more microglial cells than the cortex of non-demented controls. The number of microglia was the lowest in young control patients who died immediately after trauma. Complement factor C3d was occasionally seen in diffusely ubiquinated neurons but late complement factors were not detected in these neurons. Double staining for complement and alpha-synuclein was negative, suggesting the absence of complement in LBs. In contrast, AD plaques in the same sections showed complement factors C3c, C3d, C1q and C5-9. In conclusion, we have found no evidence that inflammatory mechanism are involved in LB formation in cerebral cortex.

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PubMed2000

Parkinson's disease: affection of brain stem nuclei controlling premotor and motor neurons of the somatomotor system.

Pathological changes which consistently develop in the lower brain stem of patients suffering from Parkinson's disease are described against the background of the internal organization and interconnections of the involved nuclei, i.e., the gigantocellular reticular nucleus, bulbar raphe nuclei, and coeruleus-subcoeruleus area. Immunoreactions against the presynaptic protein alpha-synuclein reveal not only the voluminous forms of Lewy bodies and Lewy neurites but also the otherwise inconspicuous dot- or thread-like types. These lesions develop solely in specific neuronal types. Lipofuscin- or neuromelanin-laden projection cells which at the same time generate a long, unmyelinated or sparsely myelinated axon are particularly susceptible to developing the changes. The bulbar nuclei under consideration receive strong input from supramedullary sources, above all from higher order centers of the limbic system such as the central amygdalar nucleus, periaqueductal gray, and parabrachial nuclei. In turn, they generate descending projections to premotor and motor neurons of the somatomotor system. The disease-related deterioration of both the supramedullary limbic centers and the bulbar brain stem nuclei reduces the limbic influence and markedly impairs the control of premotor and motor neurons. This functional deficit most probably contributes to the overall dysfunction of the motor system typically evolving in the course of Parkinson's disease.

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PubMed2000

Expression of nicotinic acetylcholine receptors in Alzheimer's disease: postmortem investigations and experimental approaches.

Nicotinic ligand binding studies have shown rather early that the cholinoceptive system is affected in Alzheimer's disease (AD). Today, molecular histochemistry enables one to study the nicotinic acetylcholine receptor (nAChR) subunit expression on the cellular level in human autopsy brains, in animal models and in in vitro approaches, thus deciphering the distribution of nAChRs and their role as potential therapeutic targets. The studies on the nAChR expression in the frontal and temporal cortex of AD patients and age-matched controls could demonstrate that both, the numbers of alpha4- and alpha7-immunoreactive neurons and the quantitative amount, in particular of the alpha4 protein, were markedly decreased in AD. Because the number of the corresponding mRNA expressing neurons was unchanged these findings point to a translational/posttranslational rather than a transcriptional event as an underlying cause. This assumption is supported by direct mutation screening of the CHRNA4 gene which showed no functionally important mutations. To get more insight into the underlying mechanisms, two model systems organotypic culture and primary hippocampal culture - have been established, both allowing to mimic nAChR expression in vitro. In ongoing studies the possible impact of beta-amyloid (Abeta) on nAChR expression is tested. Preliminary results obtained from primary cultures point to an impaired nAChR expression following Abeta exposure.

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PubMed2000

Pachymeningitis luetica: a case report.

Pachymeningitis luetica is extremely rare in developed countries. We describe a 41-year-old male patient with pachymeningitis luetica, multiple ischaemic infarctions, and severe hydrocephalus. The delay in making the diagnosis contributed to patient's death. Rapid diagnosis is essential on the slightest suspicion of an infection by Treponema pallidum, because timely treatment with antibiotics is effective.

Adult↗
PubMed2000

Tuberculous meningitis: pitfalls in diagnosis.

OBJECTIVES: The diagnosis of tuberculous meningitis is easily missed because the variety of symptoms give rise to problems with the differential diagnosis. MATERIAL: Five cases of difficult to diagnose tuberculous meningitis are presented. RESULTS: Several reasons for the diagnostic delay are highlighted. The fact that tuberculous meningitis is rather rare in developed countries contributes to this problem. Recommendations for a quick diagnosis are given. CONCLUSION: The diagnosis of tuberculous meningitis in developed countries is often made after a substantial delay. In case of suspicion on the diagnosis additional examination should be performed and treatment should be started immediately.

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PubMed1999

Neurogenetic correlates of Parkinson's disease: apolipoprotein-E and cytochrome P450 2D6 genetic polymorphism.

Brain tissue of 50 patients with morphological confirmed Parkinson's disease (PD), blood samples from 149 patients with clinical parkinsonism and from 96 healthy control subjects were collected. Apolipoprotein-E (apo E) and cytochrome P450 2D6 (CYP2D6) genotyping were performed by PCR followed by restriction fragment analysis. A significantly higher allele frequency of CYP2D6*4 was found in patients with PD (35%) but not with parkinsonism (14.1%) compared to control subjects (19.8%). The combined alleles frequency of CYP2D6*3 + apoE4 was significantly higher not only in the PD group (33.3%) but also in patients with parkinsonism (22.3%) compared to control subjects (1.6%). These results suggest that there is a substantial overlap not only in the clinical manifestation but also in the genetic risk factors between Parkinson's and Alzheimer's diseases.

Apolipoproteins E↗
PubMed1999

Mossy fiber involvement in progressive supranuclear palsy.

The cerebellar cortex of progressive supranuclear palsy (PSP) cases exhibited a characteristic pathology which occurred neither in healthy aged individuals nor in cases of fully developed Alzheimer's disease. All of the 11 PSP cases studied reveal altered mossy fiber excrescences containing abnormal and hyperphosphorylated tau protein. Moreover, this abnormal material also appeared in cerebellar oligodendrocytes. Accordingly, there is not only the destruction of the cerebellar output system, which is already known, but also the involvement of the cerebellar input system.

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