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Biomedical subjects

E Braak

Publications and source records attributed to E Braak.

At least 91 records · Page 5Linked to original sources

Glutamic-acid-decarboxylase-and parvalbumin-like-immunoreactive structures in the olfactory bulb of the human adult.

This study examines the distribution and morphological characteristics of glutamic-acid-decarboxylase-like (GAD)- and parvalbumin-like (PA)-immunoreactive structures in the olfactory bulb of the human adult. GAD-immunoreactive somata occurred in the glomerular layer, the external granule cell layer, the more superficial portion of the external plexiform layer, and the internal granule cell layer. The cells were small- to medium-sized. Demonstration of lipofuscin pigment revealed the presence of unpigmented as well as pigmented neurons, thus suggesting the existence of two subpopulations of GAD-positive neurons. GAD-immunoreactive puncta and/or fibers were mainly seen in the periglomerular region and the internal granule cell layer. All other layers of the bulb, as well as the intrabulbar portion of the anterior olfactory nucleus, displayed considerably less of these puncta and/or fibers. The olfactory nerve layer remained practically clear of immunoreactive material. PA-immunoreactive somata occurred in the glomerular layer and both the external and internal granule cell layer. Only a small number of immunoreactive nerve cells were encountered within the white matter or the olfactory tract. Most PA-positive neurons displayed characteristics of short axon cells whereas a few others resembled van Gehuchten cells. All of the PA-immunoreactive neurons were devoid of lipofuscin pigment. Immunoreactive puncta and fibers were present in all layers though predominating in the periglomerular region, the olfactory nerve layer, and the internal granule cell layer. The intrabulbar portions of the anterior olfactory nucleus did not show any immunoreactive structures.

Adult↗

Neurofibrillary changes confined to the entorhinal region and an abundance of cortical amyloid in cases of presenile and senile dementia.

Cases of old-aged demented individuals exhibited abundant cortical amyloid deposits but only small numbers of neurofibrillary changes. Neuritic plaques were rare or absent. Neither Ammon's horn nor isocortex revealed sufficiently large numbers of tangles to permit the diagnosis of fully developed Alzheimer's disease. Dense accumulations of neurofibrillary tangles and neuropil threads occurred only in layer Pre-alpha (II) of the entorhinal region. This pattern of cortical destruction may represent a variant of Alzheimer's disease or an initial stage of this disorder.

Aged↗

Cognitive impairment in Parkinson's disease: amyloid plaques, neurofibrillary tangles, and neuropil threads in the cerebral cortex.

Sensitive silver methods for extracellular amyloid and intraneuronal cytoskeleton abnormalities (neurofibrillary tangles and neuropil threads) were employed to examine the cortical pathology in Parkinson's disease. In cases with cognitive impairment many plaque-like amyloid deposits were found in the cerebral cortex. Neuritic plaques were rare or absent. Neither the Ammon's horn nor the isocortex revealed a sufficiently large number of tangles to permit the diagnosis of a coexisting fully developed Alzheimer's disease. Large numbers of neurofibrillary tangles and neuropil threads were only found in layer Pre-alpha of the entorhinal cortex. This layer gives rise to major portions of the perforant tract, a pathway which serves as a link in the transmission of data from isocortical association areas to the hippocampal formation. During the course of Parkinson's disease the hippocampal formation is thus endangered to become disrupted from isocortical influences. It is concluded that the cognitive impairment shown by many individuals suffering from Parkinson's disease may partly be caused by cortical lesions.

Aged↗

Alzheimer's disease: striatal amyloid deposits and neurofibrillary changes.

Sensitive silver methods were employed for the examination of extracellular amyloid and intraneuronal neurofibrillary changes in the striatum of Alzheimer's disease patients. Numerous amyloid deposits were present in the striatum whereas neuritic (senile) plaques were only rarely encountered. Many large and a few medium-sized nerve cells had neurofibrillary tangles within their somata and according to morphological criteria corresponded to local circuit neurons. Numerous argyrophilic threads in the neuropil were scattered throughout the nuclear gray matter. The striatum of non-demented individuals was virtually devoid of amyloid and neurofibrillary changes.

Adult↗

Alzheimer's disease: mismatch between amyloid plaques and neuritic plaques.

Isocortical amyloid deposits and neurofibrillary changes were studied using selective silver staining methods. Amyloid was found in plaque-like formations varying in size and shape. The distribution pattern of these plaques as seen in the silver-stained preparations was identical to that recognized by A4 protein (amyloid) immunostaining. Consecutive sections stained for amyloid and neurofibrillary changes revealed the absence of intraneuronal cytoskeleton abnormalities within the boundaries of many of the amyloid plaques. Congo red preparations did not show these plaques and the tissue within the range of the plaques did not reveal any conspicuous neuropil distortions and/or glial cell accumulations. Hence, a considerable proportion of the amyloid plaques do not correspond to and should carefully be distinguished from 'primitive', 'mature', and 'burned out' types of neuritic (senile) plaques.

Aged↗

The presubicular region in Alzheimer's disease: topography of amyloid deposits and neurofibrillary changes.

Specific silver impregnation techniques for extracellular amyloid and intraneuronal neurofibrillary changes were used to examine the presubiculum in Alzheimer victims. Extended amyloid clouds in the absence of neurofibrillary changes were noted in the parvopyramidal layer of the presubiculum proper. The corresponding layer in the parasubiculum, in contrast, showed many neurofibrillary tangles and neuropil threads in the absence of amyloid. The transsubicular parvopyramidal layer contained both amyloid deposits and neurofibrillary changes. This severe involvement of all subdivisions of the presubicular region in Alzheimer's disease is considered to impair functions of the Papez circuit.

Alzheimer Disease↗

Alzheimer's disease: areal and laminar pathology in the occipital isocortex.

Sensitive and specific silver methods for demonstration of (1) amyloid and/or precursors of amyloid and (2) neurofibrillary changes were applied to examine the pathology revealed by the occipital isocortex in cases of Alzheimer's disease and age-matched controls. In general, amyloid and/or precursors of amyloid are encountered in plaque-like formations. Large numbers of amyloid plaques occur in layers that only occasionally harbor neuritic plaques. Amyloid deposits can be found in abundance in the occipital cortex of demented individuals exhibiting an only sparse number of neuritic plaques. In demented individuals the striate area contains almost as much amyloid as the parastriate area or the peristriate region. Neurofibrillary changes are encountered in neuritic plaques, neurofibrillary tangles, and neuropil threads. Neuritic plaques are predominantly found in layers II and III. Their density changes even within the boundaries of architectonic units. Large numbers of plaques are found in the cortex covering the depth of the sulci. The number of neurofibrillary tangles increases abruptly when passing the striate/parastriate and the parastriate/peristriate boundaries. The neuropil threads may densely fill a layer without the presence of neurofibrillary tangles (layer V of the striate area). Neuropil threads contribute a substantial part to the total amount of the intraneuronally deposited pathological material.

Aged↗

Alzheimer's disease: amyloid plaques in the cerebellum.

Two specific silver-staining methods demonstrating either extracellular amyloid and/or precursors of amyloid or intraneuronal neurofibrillary changes were used to examine cerebellar pathology in cases of presenile and senile dementia of the Alzheimer type, cases of Down's syndrome, and non-demented controls. The sensitivity of the techniques permitted visualization of large numbers of amyloid deposits in the cerebellar cortex of demented individuals. Similarly large numbers of amyloid deposits were not found in the cerebella of non-demented individuals. Neurofibrillary changes were absent. The majority of amyloid plaques occurred in the molecular layer. Quite a number of these displayed large diameters extending from the upper surface down to the Purkinje cell layer. Within the granular layer and white matter the plaques were less frequently encountered and they were less voluminous than those of the molecular layer. The cerebellar amyloid plaques were morphologically different and could easily be distinguished from the cerebellar plaques found in transmissible spongiform encephalopathies.

Adolescent↗

Changes within the basal nucleus in Parkinson's disease.

The magnocellular nuclei in the basal forebrain--the medial septal nucleus, the nucleus of the diagonal band, and the basal nucleus within the substantia innominata--are tightly connected with each other. Large multipolar neurons clearly predominating in number can be differentiated from a spindle-shaped and a small globular type of neuron on account of their typical pattern of lipofuscin pigmentation. As an additional feature some of the multipolar neurons exhibit intracytoplasmic acidophilic granules. At the ultrastructural level, these granules reveal a homogeneous substructure, and they are occasionally located within mitochondria. The percentage of large multipolar neurons displaying acidophilic granules varies in a topographical manner (medial septal nucleus and vertical limb nucleus of the diagonal band: 10%, horizontal limb nucleus of the diagonal band and anteromedial subnucleus of the basal nucleus: 36%, posterolateral subnucleus of the basal nucleus: 54%). In parkinsonian cases a significant decrease of granule-bearing neurons within the posterolateral subnucleus of the basal nucleus is noted. This decrease might be associated with the appearance of neurons containing Lewy-bodies. It is also conceivable that the granule-bearing neurons show a higher vulnerability and underlie neuronal death. Analyzing the lipofuscin pigmentation within the two subnuclei of the basal nucleus in parkinsonian cases, one notices that the number of large multipolar neurons displaying pigment granules in a dendritic stem is significantly higher than in controls. Moreover, it is apparent that the degree of this pigment penetration is more pronounced in cases of Parkinson's disease. These alterations may be interpreted as a sign of plasticity of this neuronal population.

Basal Ganglia↗

Neuropeptide Y-like immunoreactive neurons in the human olfactory bulb.

Neuropeptide Y-like (NPY) immunoreactivity was localized in the adult human olfactory bulb by the unlabeled antibody enzyme (peroxidase anti-peroxidase; PAP) technique in vibratome sections. The majority of NPY-immunoreactive somata was localized in the white matter surrounding the anterior olfactory nucleus. Immunoreactive neurons were less numerous within the anterior olfactory nucleus and within the olfactory bulb layers. NPY-immunoreactive fibres were present in the white matter, the anterior olfactory nucleus, and in the olfactory bulb layers. Fibres within the white matter were generally aligned in a straight path parallel to the long axis of the olfactory bulb and tract. Fibres within the anterior olfactory nucleus showed no clear orientation and displayed numerous branching points. Coiled plexus of NPY-immunoreactive fibres were present in the glomerular layer of the olfactory bulb. Additional characteristics of the NPY-immunoreactive neurons were studied after decolouring the chromogen and restaining the sections with aldehydefuchsin to demonstrate the presence of lipofuscin granules and also with gallocyanin chrome alum to stain the Nissl substance. This analysis showed that the neurons belong to the class of non-pigmented nerve cells.

Aged↗

Somatostatin-like immunoreactivity in non-pyramidal neurons of the human entorhinal region.

The distribution of somatostatin-immunoreactive cells and processes throughout the human entorhinal region and subjacent white matter was examined either by the unlabelled antibody-enzyme method or by the avidin-biotin method. The brain slices were obtained at autopsy with a short post-mortem delay. The majority of somatostatin immunoreactive nerve cells was found in the inner principal layer and subjacent white matter. In addition, individually scattered immunoreactive neurons were observed in both the outer principal layer and lamina dissecans. The immunoreactive perikarya varied in shape and ranged in size from 10 to 30 micron. Without exception the neurons could be classified as belonging to the group of non-pyramidal neurons. Each neuron gave rise to a few thick dendrites and a thin axon with a beaded appearance. In the adult human brain, the pattern formed by lipofuscin granules deposited in the nerve cells can be considered characteristic for the type of the neuron. Therefore, immunoreactive perikarya were documented, destained of chromogen and restained to demonstrate lipofuscin pigment and basophilic substance. It became evident from these studies that the previously immunoreactive cells were characterized by a large rounded and eccentrically located nucleus, sparse basophilic substance and, in most cases, a lack of lipofuscin granules. A few of the immunoreactive cells were laden with coarse pigment granules. The findings permit classification of entorhinal somatostatin-immunoreactive neurons as either non-pigmented or pigment-laden non-pyramidal neurons.

Aged↗

Somatostatin-14-like immunoreactive neurons and fibres in the human olfactory bulb.

This study describes the morphological features and the distribution pattern of neurons in the human olfactory bulb which are immunoreactive for an antiserum against the neuropeptide somatostatin-14. Immunoreactive nerve cell bodies were mainly found in the white matter surrounding the cell clusters of the anterior olfactory nucleus. Some immunoreactive neurons were also found scattered throughout the anterior olfactory nucleus and the deeper parts of the inner granule cell layer. Only a few immunoreactive neurons were localized in the glomerular layer and the outer granule cell layer. Immunoreactive fibres were found in all layers of the olfactory bulb. In addition, an impressive number of coiled and kinked immunoreactive fibres were localized within the anterior olfactory nucleus forming a dense plexus. Accumulations of twisted and coiled branches of immunoreactive fibres were rarely found either surrounding or within the olfactory glomerula. The characteristics of somatostatin-14 immunoreactive neurons as seen in the combined pigment-Nissl preparation were studied after decolourizing the chromogen and restaining the preparations with aldehydefuchsin in order to demonstrate the lipofuscin pigment and gallocyanin chrome alum for Nissl material. About 90% of the immunoreactive neurons studied in this manner turned out to be devoid of lipofuscin granules. The remaining 10% displayed different patterns of pigmentation. These findings suggest the presence of different types of somatostatin-14-like immunoreactive neurons in the olfactory bulb of the human adult.

Adult↗

Silver impregnation of Alzheimer's neurofibrillary changes counterstained for basophilic material and lipofuscin pigment.

A method is described in which selective silver staining of Alzheimer's neurofibrillary changes is combined with staining of cell nuclei, Nissl material, and lipofuscin granules. Formalin fixed, paraffin embedded sections of human autopsy tissue are silver stained according to a method proposed by Gallyas. Lipofuscin is stained by crotonaldehyde fuchsin following performic acid oxidation. Nissl substance is visualized by either Darrow red or gallocyanin-chrome alum staining. Architectonic units showing the specific pathology and the neuronal types prone to develop the neurofibrillary changes can be recognized using this technique.

Alzheimer Disease↗

Argyrophilic grains: characteristic pathology of cerebral cortex in cases of adult onset dementia without Alzheimer changes.

Brains from 56 individuals suffering from adult onset dementia and devoid of macroscopically detectable infarctions were examined. Forty brains showed the characteristic cytoskeleton changes of Alzheimer's disease. Eight brains failed to reveal considerable numbers of neuritic plaques, neurofibrillary tangles, and neuropil threads, but these brains showed the presence of abnormal and intensely argyrophilic grains loosely scattered throughout the neuropil. Abundant numbers of these small spindle-shaped grains were encountered within the pyramidal layers of CA1 and layer Pre-beta of the entorhinal region. Eight brains showed both the argyrophilic grains and the neurofibrillary changes of the Alzheimer type. The appearance of argyrophilic grains within the neuropil is considered a morphological substrate of an unknown disease associated with adult onset dementia.

Aged↗

The hypothalamus of the human adult: chiasmatic region.

The human hypothalamus can be divided into a chiasmatic region, a tuberal region, and a mamillary region. The chiasmatic region comprises the magnocellular neurosecretory nuclei, several nuclei that are mainly formed of small nerve cells, and an ill-defined nerve cell assembly referred to as the chiasmatic gray. Small to medium-sized bipolar nerve cells predominate in the chiasmatic gray. With the use of Nissl preparations counterstained for demonstration of lipofuscin pigment, four types of neurons have been distinguished. Type I cells contain coarse and intensely stained lipofuscin granules. Type II cells are characterized by dense accumulations of small granules. Type III neurons harbour only a fine scattering of dust-like granules while type IV neurons are devoid of pigment. Pigmentoarchitectonic analysis of the chiasmatic region reveals the presence of eight nuclei embedded in or partially surrounded by the chiasmatic gray. The intermediate nucleus is a small compact accumulation of non-pigmented nerve cells located at the level of the optic chiasm half way between the paraventricular nucleus and the supraoptic nucleus. The periventricular nucleus and the uncinate nucleus are mainly formed of small pigment-laden type I and type II cells and appear as an anterior, respectively lateral extension of the paraventricular nucleus. Besides non-specific small cells, three neuronal types can be distinguished in the paraventricular nucleus on account of characteristic differences in their pigmentation. The supraoptic nucleus is formed of only two types of nerve cells. The cuneiform nucleus extends from the supraoptic nucleus to the ependymal lining of the third ventricle separating the suprachiasmatic nucleus from the retrochiasmatic nucleus. The suprachiasmatic nucleus contains the smallest neurons of the region. Cells of this nucleus are devoid of lipofuscin pigment. The retrochiasmatic nucleus is formed of a heterogeneous population of small and unusually large nerve cells. Numerous melanin-containing nerve cells and accumulations of nerve cells belonging to the lateral tuberal nucleus can be encountered within the boundaries of this nucleus as well. The technique and the data presented provide a basis for investigations of the aged and the diseased human brain.

Adolescent↗

Occurrence of neuropil threads in the senile human brain and in Alzheimer's disease: a third location of paired helical filaments outside of neurofibrillary tangles and neuritic plaques.

Paired helical filaments, pathologically changed components of the cytoskeleton of human nerve cells, are demonstrated by a specific silver staining technique, immunostaining and electron microscopy. Accumulations of these filaments are found in the telencephalic cortex of old-aged individuals and patients suffering from Alzheimer's disease. Apart from neurofibrillary tangles and neuritic plaques, paired helical filaments are encountered in neuropil threads. At this third location, pathological filaments occur in small and inconspicuous profiles scattered throughout both allocortical and isocortical areas. The pattern of distribution and packing density of neuropil threads varies between different cortical areas and layers.

Aged↗

Glutamic acid decarboxylase immunoreactivity in sector CA1 of the human Ammon's horn.

The distribution of glutamic acid decarboxylase (GAD) immunoreactive neurons, fibres and punctae in sector CA 1 of the adult human Ammon's horn was studied in Vibratome sections (40 micron thick) of tissue obtained at surgery and autopsy. On light microscopical examination, the material did not show pathological changes. The antibody was visualized by the unlabelled antibody enzyme method. GAD-immunoreactive neurons, fibres and punctae were present in all layers. Most immunoreactive neurons were located in the stratum pyramidale and stratum lacunosum. Their size ranged from 8 microns in the stratum lacunosum to about 50 microns in the stratum oriens. The somata offered a wide range of shapes, multiform to fusiform with the long axis aligned parallel or vertically to the alveus. All somata belonged to the heterogeneous group of non-pyramidal neurons. The dendrites either radiated in all directions or tended to run in two opposite directions. After bleaching the chromogen and staining for lipofuscin pigment granules and basophilic material, it turned out that within the stratum pyramidale all formerly GAD-immunoreactive neurons belonged to the group of lipofuscin-laden non-pyramidal neurons. Within the other layers, a few formerly GAD-immunoreactive neurons were devoid of lipofuscin pigment. The highest density of GAD-immunoreactive punctae was found in the stratum lacunosum. In addition to numerous GAD-immunoreactive punctae in the pyramidal layer and in the stratum radiatum there were thin GAD-immunoreactive fibres of varying length extending into various directions.

Adult↗