White matter changes in HIV-1 infected brains: a combined gross anatomical and ultrastructural morphometric investigation of the corpus callosum.

Objective: The HIV-1 associated cognitive/motor complex is characterized by cognitive, motor and behavioral disturbances. Besides a significant loss of neurons in the cerebral cortex and subcortical nuclei, a possible morphological substrate of this complex is also given by changes of the white matter as seen in HIV-1 leucoencephalopathy (HIVL), which is characterized by widespread diffuse pallor of myelin and the presence of gliomesenchymal nodules with multinucleated giant cells.

Methods: The corpus callosum as a sensitive marker for damage of the cerebral white matter was investigated by morphometry both at the macroscopic and electronmicroscopic level.

Histopathological abnormalities in ocular blood vessels of CADASIL patients.

Purpose: To assess histopathological findings in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Design: Case reports and histopathological evaluation of enucleated eyes.

Methods: Four eyes from two CADASIL patients were enucleated at autopsy and prepared for histopathological analysis using light and electron microscopy.

Expression of tenascin-C in various human brain tumors and its relevance for survival in patients with astrocytoma.

Background: Tenascin-C (TN-C), a large extracellular matrix (ECM) glycoprotein with a molecular weight of 180-250 kilodaltons, is present in several normal adult tissues. TN-C is up-regulated during embryogenesis, in wound healing, and in tumor tissues. Glioblastoma multiforme (GBM) is the most frequent and malignant astrocytic tumor comprised of poorly differentiated, neoplastic astrocytes.

Apoptosis in the basal ganglia of the developing human nervous system.

Programmed cell death (PCD) plays a crucial role in the development of the central nervous system through controlling neuronal numbers and adequate synaptic connections. PCD has been considered to occur in the form of apoptosis. To examine how apoptosis occurs in the developing human brain, we performed a morphometric TUNEL study, using a commercially available kit (ApopTag Kit, Oncor Inc.

Two novel point mutations of mitochondrial tRNA genes in histologically confirmed Parkinson disease.

Mutations in mitochondrially encoded tRNA genes have been described in a variety of neurological disorders. One such mutation, the A to G transition at nucleotide position 4336 of the mitochondrial tRNA(Gln) gene, has been associated with both Alzheimer and Parkinson disease. We have now performed a complete sequence analysis of all 22 mitochondrially encoded tRNA genes in 20 cases of histologically proven idiopathic Parkinson disease.

The alpha1-antichymotrypsin A-allele in German Parkinson disease patients.

An increased frequency of the A-allele of the alpha-antichymotrypsin (ACT) gene has been recently described in Japanese patients suffering from Parkinson disease (PD). In the present study, we have analyzed 62 German PD patients with regard to their ACT and APOE genotypes and compared them to 53 controls without clinical or pathological evidence of neurodegenerative disease. The A-allele frequency was 47% in PD patients compared to 54% in control cases excluding ACT as a major susceptibility factor for PD in the Caucasian population.

Neuronal damage of the substantia nigra in HIV-1 infected brains.

Extrapyramidal motor disorders are frequently noted in HIV-1-infected patients. In the present study, the substantia nigra was analyzed morphometrically to detect neuronal changes which might contribute to the pathogenetic mechanisms causing extrapyramidal motor dysfunction in HIV-1-infected patients. The numerical density and the size of pigmented, non-pigmented small, and non-pigmented large neurons in four nuclei of the substantia nigra pars compacta (antero-medial, antero-intermediolateral, postero-lateral, and postero-medial nuclei) in HIV-1-infected patients and in age-matched normal controls were determined.

Histopathology and APOE genotype of the first Alzheimer disease patient, Auguste D.

Alois Alzheimer published two papers on the disease which was named after him by Emil Kraepelin in 1910. Each of these papers contains clinical and pathological data on a patient Alzheimer had seen at the hospital. We have previously reported on the rediscovery of tissue sections from Alzheimer's second published case of Alzheimer disease, Johann F.

Novel mutations of mitochondrial complex I in pathologically proven Parkinson disease.

Complete sequence analysis of all mitochondrial complex I genes was performed in 22 cases of neuropathologically confirmed idiopathic Parkinson disease (PD). DNA from the substantia nigra was used as a template for polymerase chain reaction-based genomic sequencing. Seven novel mutations causing the exchange of amino acids were detected in subunit genes ND1 (3992 C/ T, 4024 A/G), ND4 (11253 T/C, 12084 C/T), ND5 (13711 G/A, 13768 T/C), and ND6 (14582 T/C).

Reanalysis of the first case of Alzheimer's disease.

When a disease becomes as important as Alzheimer's dementia, there is a natural interest in its medical history and in the origin of the underlying disease concept. Key to understanding Alois Alzheimer's views on the disease, which was named after him, are the histological sections of the cases he saw. This histological material was rediscovered in Munich in 1992 and 1997 (Neurogenetics 1997, 1:73-80; 1998, 1:223-228).

Analysis of mitochondrial targeting sequence and coding region polymorphisms of the manganese superoxide dismutase gene in German Parkinson disease patients.

Two polymorphisms of the MnSOD gene, Ile58Thr and Ala9Val, have been associated with Parkinson disease (PD). The Ile58Thr amino acid exchange affects the stability at the tetrameric interface of the enzyme and reduces the enzymatic activity of MnSOD while the Ala/Val substitution at position -9 of the mitochondrial targeting sequence (MTS) may lead to misdirected intracellular trafficking. We have analyzed 63 German Caucasian PD patients for possible sequence variation in the MTS as well as in exon 3 of the MnSOD gene.

Differential expression of MHC class II molecules by microglia and neoplastic astroglia: relevance for the escape of astrocytoma cells from immune surveillance.

There is increasing evidence that microglia serve as antigen presenters in the human CNS. Although the occurrence of MHC class II immunoreactive cells has been reported in astrocytic gliomas, the relative contribution of microglia to this cell population has not been studied in detail. Using computer-assisted image analysis, we have investigated the expression of MHC class II molecules and of the microglia/macrophage markers Ki-MIP, RCA-1, KP1 and iba1, in 97 astrocytic gliomas comprising all WHO grades to answer the question whether there is a correlation between tumour grade and the number of MHC class II positive microglia/macrophage profiles.

Microglia and the development of spongiform change in Creutzfeldt-Jakob disease.

Recent in vitro experiments suggest that neurotoxicity of the prion protein is dependent on the presence of microglia. We have studied 11 cases of Creutzfeldt-Jakob disease (CJD) using immunocytochemistry in combination with computerized image analysis to clarify the relationship between spongiform change and microglial activation. MHC class II-positive microglia were almost exclusively confined to cortical gray matter where the neuropil area occupied by these cells exceeded that of controls more than 350-fold.

Long-lasting perivascular accumulation of major histocompatibility complex class II-positive lipophages in the spinal cord of stroke patients: possible relevance for the immune privilege of the brain.

Six cases of middle cerebral artery occlusion are presented in which the cellular changes accompanying descending degeneration of the lateral corticospinal tract were studied at different time points (5 days-10 years) following the insult. Microglia and perivascular cells were found to ingest large amounts of myelin degradation products, while expressing high levels of major histocompatibility complex (MHC) class II molecules. Activation of perivascular macrophages, as indicated by increased class II expression, lasted for many years and appeared to follow down-regulation of both phagocytic activity and class II expression on parenchymal microglia.

Association of the mitochondrial tRNA(A4336G) mutation with Alzheimer's and Parkinson's diseases.

Alzheimer's and Parkinson's diseases (AD, PD) are among the most common neurodegenerative disorders in adults. Both AD and PD have a complex aetiology, and it is widely considered that genetic factors, acting independently or in concert with other genetic and/or environmental factors, modify the risk of developing them. While the apolipoprotein E (ApoE) epsilon 4 allele represents an established risk factor for familial and sporadic late-onset AD, it has been suggested that a common polymorphism in the alpha 1-antichymotrypsin gene modifies the ApoE epsilon 4 dosage effect in AD.

Kaposi's sarcoma in the cerebellum of a patient with AIDS.

A case of Kaposi's sarcoma in the left cerebellar hemisphere of a patient with AIDS is presented. The lesion was not detected with imaging techniques in the patient who, during the clinical course, did not show neurological signs and symptoms. This small nodular lesion was only revealed at autopsy.

Rediscovery of the case described by Alois Alzheimer in 1911: historical, histological and molecular genetic analysis.

In 1911, Alois Alzheimer published a detailed report (Zbl. ges. Neurol.

On the question of apoptosis in the parkinsonian substantia nigra.

Apoptosis has been postulated as a mechanism of nerve cell death in Parkinson's disease. In the present study, the substantia nigra of 22 neuropathologically confirmed Parkinson cases and 8 control brains was studied using the in situ end-labeling (TUNEL) method. About 50% of parkinsonian brains showed a small number of TUNEL-positive glial cells in the substantia nigra, whereas no neurons showed convincing TUNEL positivity or any morphological signs of apoptosis.

Defects of cytochrome c oxidase in the substantia nigra of Parkinson's disease: and immunohistochemical and morphometric study.

Defects of respiratory chain complexes were considered as possible pathogenetic mechanisms in Parkinson's disease (PD). Changes of cytochrome c oxidase (COX) in four different nuclei of the substantia nigra of 8 PD cases and 10 age-matched controls were investigated by means of morphometry and immunohistochemistry. Pigmented neurons with COX defects were randomly distributed within the the four nuclei of PD cases, but only in the posterolateral nucleus was the numerical density of pigmented neurons with COX defects significantly increased compared with controls.

Cytochrome c oxidase defects of the human substantia nigra in normal aging.

Based on morphological, biochemical, and molecular biologic analyses, degeneration of the dopaminergic nigrostriatal system has been reported to occur with normal aging. In the present study, the substantia nigra of 36 human brains with normal aging was investigated by means of morphometry and immunohistochemistry. The anteromedial (Am), anterointermediolateral (Ail), posteromedial (Pm), and posterolateral (Pl) nuclei of the substantia nigra were analyzed using antibodies directed against the subunits II/III of cytochrome c oxidase (COX), the complex IV of the respiratory chain.

Immunhistological evaluation of Creutzfeldt-Jakob disease with reference to the type PrPres deposition.

German patients suspected of having Creutzfeldt-Jakob disease (CJD) and related diseases were studied pathologically. The immunohistochemical findings after hydrolytic autoclaving pretreatment sensitively detected the synaptic-type deposition of the protease-resistant isoform of the prion protein (PrPres which thus served to establish the consensus diagnosis of CJD.

Degeneration of the cerebellar dentate nucleus and the inferior olivary nuclei in HIV-1-infected brains: a morphometric analysis.

Motor dysfunction is frequently noted in human immunodeficiency virus type 1 (HIV-1)-infected patients. Until recently, neuropathological changes found in the basal ganglia were advanced as pathogenetic mechanisms. In the present study, further brain structures involved in motor control were analyzed morphometrically.

The apolipoprotein E epsilon 4 allele in Parkinson's disease with Alzheimer lesions.

The association between the apolipoprotein E (ApoE) epsilon 4 allele and Parkinson's disease (PD) with coexistent dementia has remained controversial. We determined ApoE allele frequencies in 35 subjects with neuropathologically confirmed Lewy body Parkinsonism with and without concomitant Alzheimer lesions, 27 patients with Alzheimer's disease (AD), and 54 controls without neurodegenerative disease. We hypothesized that if AD lesions in PD evolve by the same pathomechanism as in "pure AD," the ApoE epsilon 4 allele frequency in PD with AD lesions (PD+AD) and pure AD should be similar.

Vascular changes in the cerebral cortex in HIV-1 infection. II. An immunohistochemical and lectinhistochemical investigation.

In human immunodeficiency virus 1 (HIV-1)-infected patients, a hypoperfusion is seen by SPECT analyses in different brain regions but a specific pattern for the predominance of a specific brain region has not been found. The vessels of the cerebral cortex of the frontal, temporal, parietal, and occipital lobes of acquired immunodeficiency syndrome (AIDS) brains and control brains were analyzed by immunohistochemistry and lectin histochemistry. Immunohistochemistry was performed for collagen IV, laminin (basal lamina), and factor VIII (endothelial cell) and lectin histochemistry [Ricinus communis agglutinin (RCA-I), Ulex europaeus agglutinin (UEA-I), wheatgerm agglutinin (WGA) and soybean agglutinin (SBA)] was used to study changes of glycoproteins in the endothelial cell membrane.