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.

Apolipoprotein E isoforms and the development of low and high Braak stages of Alzheimer's disease-related lesions

In recent research, apolipoprotein-E (apoE) polymorphism has been shown to influence the formation of neurofibrillary changes and the accumulation of beta/A4-amyloid, the histopathological hallmarks of Alzheimer's disease (AD). Clinical studies associate the apoE allele epsilon4 with earlier onset of the disease, although the clinical speed of progression remains unchanged. Time course estimates have also provided evidence which indicates that the clinical phase of AD constitutes only 10-20% of the total time span needed for the development of this slowly progressing degenerative brain disorder. Due to the lack of reliable clinical tests for the detection of pre-symptomatic stages of AD, we…

Involvement of the cholinergic basal forebrain nuclei in spinocerebellar ataxia type 2 (SCA2)

Aims: Spinocerebellar ataxia type 2 (SCA2) belongs to the CAG repeat or polyglutamine diseases. Along with a large variety of motor, behavioural and neuropsychological symptoms the clinical picture of patients suffering from this autosomal dominantly inherited ataxia may also include deficits of attention, impairments of memory, as well as frontal-executive and visuospatial dysfunctions. As the possible morphological correlates of these cognitive SCA2 deficits are unclear we examined the cholinergic basal forebrain nuclei, which are believed to be crucial for several aspects of normal cognition and may contribute to impairments of cognitive functions under pathological conditions. Methods: …

Klinische Aspekte der "argyrophilic grain disease"

Argyrophilic grain disease (AGD) is a frequently occurring degenerative illness of the aging human brain. It is accompanied by progressive pathological alterations of the cytsokeleton which are traceable to an abnormal phosphorylation of the microtubule associated tau protein. Histologically, it is possible with the help of suitable staining techniques to identify pathognomonic spindle-shaped cellular inclusions (argyrophilic grains). These cellular inclusions display a typical cortical as well as subcortical distribution pattern. The goal of the present study is the retrospective evaluation of the clinical findings from 53 individuals with neuropathologically demonstrable AGD-related chang…

Ontogeny of the human amygdala.

Data on the fetal development of the human amygdala is reviewed with special reference to major ontogenetic events. In the fifth gestational month, the inferior portion of the amygdala reveals cell-dense columns merging with the ganglionic eminence (proliferative zone) in Nissl-stained sections. These columns contain vimentin-positive fibers and can therefore be regarded as migrational routes. In the sixth and seventh months, distinct reorganization of the cytoarchitectonics takes place. The sequential occurrence of afferens can be visualized using anti-GAP-43; moreover, outgrowing axons appear to reach the periphery of the ganglionic eminence. The latter may thus represent an intermediate …

Expression of MAP1a and MAP1b in the ganglionic eminence and the internal capsule of the human fetal brain.

The expression of microtubule-associated proteins 1a and 1b (MAP1a and 1b) were investigated in two transient structures, the ganglionic eminence (GE) being a prominent part of the telencephalic proliferative zone and the perireticular nucleus (PR) within the internal capsule (IC). Anti-MAP1a immunolabels PR neurons from 18 weeks of gestation (wg) onwards, whereas anti-MAP1b immunolabels long IC fibers between 18 and 22 wg. MAP1b is further present in thalamic fibers that seem to terminate at the medial margin of the GE, in a moderate number of cells of the GE and its medial extension, the gangliothalamic body (GTB). From 26 to 33 wg MAP1b is expressed in short fiber bundles of the IC, a fe…

Diseases of the vertebral arteries.

Case reports and postmortem neuropathological findings of a wide spectrum of diseases affecting the vertebral arteries, in particular vasculitis, traumatic lesions, degenerative changes and congenital abnormalities, are discussed.

HIGH PROPORTION OF DEMENTIA WITH LEWY BODIES IN THE POSTMORTEMS OF A MENTAL HOSPITAL IN GERMANY

Objective. Dementia with Lewy bodies (DLB) is under-recognized in Germany. No data on the number of patients suffering from this condition in Germany are available at present. We were interested in the proportion of DLB in the postmortems of demented inpatients in the care of a psychogeriatric service. Design. In a retrospective study we examined consecutive postmortems of inpatients who died in one mental hospital. Setting. A suburban and rural old age psychiatry service in Germany. Patients. 103 consecutive postmortems had been performed from 9/1987 to 6/1995. Fifty-nine (57.3%) of all cases warranted the clinical diagnosis of dementia (DSM-III-R). Measures. The causes of dementia were ex…

Neurofibrillary tangles and neuropil threads as a cause of dementia in Parkinson’s disease

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common age-related degenerative disorders of the human brain. Both diseases involve multiple neuronal systems and are the consequences of cytoskeletal abnormalities. In AD susceptible neurons produce neurofibrillary changes, while in Parkinson’s disease, they develop Lewy bodies. In AD six developmental stages can be distinguished on account of the predictable manner in which the neurofibrillary changes spread across the cerebral cortex. During the course of PD numerous limbic determined parts of the brain undergo specific lesions regulating endocrine and autonomic functions. In general, the extranigral destructions are in t…

Monoclonal antibodies SMI 311 and SMI 312 as tools to investigate the maturation of nerve cells and axonal patterns in human fetal brain

Neurofilaments, which are exclusively found in nerve cells, are one of the earliest recognizable features of the maturing nervous system. The differential distribution of neurofilament proteins in varying degrees of phosphorylation within a neuron provides the possibility of selectively demonstrating either somata and dendrites or axons. Non-phosphorylated neurofilaments typical of somata and dendrites can be visualized with the aid of monoclonal antibody SMI 311, whereas antibody SMI 312 is directed against highly phosphorylated axonal epitopes of neurofilaments. The maturation of neuronal types, the development of area-specific axonal networks, and the gradients of maturation can thus be …

Reduced basal and stimulated (isoprenaline, Gpp(NH)p, forskolin) adenylate cyclase activity in Alzheimer's disease correlated with histopathological changes

Cyclic adenosine monophosphate (cAMP) is an adenylate cyclase borne second messenger involved in basic metabolic events. The beta-adrenoceptor sensitive adenylate cyclase was studied in post-mortem hippocampi of controls and Alzheimer patients. Virtually identical subsets of each hippocampus homogenate were stimulated by 100 mumol isoprenaline, Gpp(NH)p and forskolin, respectively, in presence of an ATP-regenerating system. The determination of cAMP formed was carried out by means of a radioassay. The observed significant 50% reduction in basal as well as in stimulated adenylate cyclase activity in Alzheimer's disease is negatively correlated with semiquantitative evaluations of amyloid pla…

Histological Findings in Coil-packed Experimental Aneurysms 3 Months after Embolization

ABSTRACT OBJECTIVE Knowledge regarding tissue reactions within coil-packed aneurysms is poor. The purpose of this study was to analyze histological changes in a chronic experimental bifurcation aneurysm model that might explain the protective effect of Guglielmi detachable coils. METHODS The aneurysms were produced by means of a venous graft pouch at a surgically created bifurcation of the carotid artery in the neck of rabbits. After 3 weeks, embolization with Guglielmi detachable coils was performed in the treatment group but not in the control group (seven rabbits each). At the time of embolization, six of seven treated aneurysms were completely occluded according to radiological criteria…

Degeneration of the Cerebellum in Huntington's Disease (HD): Possible Relevance for the Clinical Picture and Potential Gateway to Pathological Mechanisms of the Disease Process

Huntington's disease (HD) is a polyglutamine disease and characterized neuropathologically by degeneration of the striatum and select layers of the neo- and allocortex. In the present study, we performed a systematic investigation of the cerebellum in eight clinically diagnosed and genetically confirmed HD patients. The cerebellum of all HD patients showed a considerable atrophy, as well as a consistent loss of Purkinje cells and nerve cells of the fastigial, globose, emboliform and dentate nuclei. This pathology was obvious already in HD brains assigned Vonsattel grade 2 striatal atrophy and did not correlate with the extent and distribution of striatal atrophy. Therefore, our findings sug…

Results of 200 intracranial stereotactic biopsies

200 stereotactic biopsies were evaluated. The validity of the intraoperative histopathological results were compared with the final diagnosis using conventional embedding and staining techniques. Further comparison between the histology of the biopsy and the post mortem or open operative findings were possible in 41 cases. Discrepancy was found in one case regarding the tumor detection, and in three cases regarding the tumor grading. The mortality in our patients was 1% and the morbidity 3%. Stereotactical biopsy had a low risk even in deep brain regions such as basal ganglia, mesencephalon, and pons. At the same time the high histologic validity makes the CT-guided stereotactical biopsy re…

Beta-adrenoceptor density and subtype distribution in cerebellum and hippocampus from patients with Alzheimer's disease

beta-Adrenoceptor density and beta 1- and beta 2-subtype distribution were examined in hippocampi and cerebella from patients with Alzheimer's disease (AD/SDAT). Tissues from age-, sex and post-mortem delay matched non-demented patients served as controls. The total beta-adrenoceptor density as evaluated in saturation experiments with the hydrophilic radioligand [3H]CGP 12177 was higher in hippocampal (36-39 fmol/mg protein) than cerebellar tissues (20-21 fmol/mg), however, no differences were found in either brain region between AD/SDAT patients and controls. Subtype distribution using the highly selective beta 1-adrenoceptor antagonist CGP 20712A revealed a slightly higher proportion of b…

Evolution of brain abscess in cats formation of capsule and resolution of brain edema

Brain abscess evolution was studied in an experimental model in the cat correlating the computed tomographic scan appearance with intracranial pressure, brain edema and histopathological findings. Brain inflammation was produced by direct inoculation of Staphylococcus aureus into the white matter. Abscesses developed in all animals. The ring enhancement around the necrotic focus seen at an early stage after contrast-medium injection cannot be equated with capsule formation as long as the abscess diameter increased. Parallel to the acute stage of abscess, the intraventricular pressure increased due to the rising mass effect and the spreading edma. The morphological investigations revealed on…

Magnetic resonance imaging in primary cerebral neuroblastoma

Ultrastructural study of the retina in late infantile metachromatic leukodystrophy.

The autopsy of a 2-year-old girl revealed a clinically unrecognized metachromatic leukodystrophy (MLD) due to an aryl-sulfatase A deficiency, characteristically affecting the central and peripheral nervous system by demyelination and by accumulation of metachromatic material. The retina though reported clinically as normal, showed the same demyelinating process in the optic nerve including the papilla but an additional intraneuronal storage of MLD-typical lysosomal residual bodies in ganglion cell perikarya of the retina. Cells of the bipolar and photoreceptor layers as well as pigment epithelial cells were not affected by MLD-specific lysosomal storage. Thus, sulfatides seem to play a part…

Pattern of brain destruction in Parkinson's and Alzheimer's diseases

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common age-related degenerative disorders of the human brain. Both diseases involve multiple neuronal systems and are the consequences of cytoskeletal abnormalities which gradually develop in only a small number of neuronal types. In AD, susceptible neurons produce neurofibrillary tangles (NFTs) and neuropil threads (NTs), while in PD, they develop Lewy bodies (LBs) and Lewy neurites (LNs). The specific lesional pattern of both illnesses accrues slowly over time and remains remarkably consistent across cases. In AD, six developmental stages can be distinguished on account of the predictable manner in which the neurofibrillar…

The Lipofuscin Content of Nerve Cells of the Inferior Olivary Nucleus in Alzheimer's Disease

Lipofuscin, the age pigment, is of interest in Alzheimer's disease because of its property to accumulate in neurons and because of the hypothesis that Alzheimer's dementia is a kind of premature ageing. The amount of intraneuronal lipofuscin in the inferior olivary nucleus of 20 brains from patients with histologically confirmed Alzheimer's disease according to the CERAD protocol and of 20 controls has been measured microfluorometrically. Patients and controls were matched for age. The amount of lipofuscin in the neurons of the inferior olivary nucleus did not differ significantly between the cases of Alzheimer's disease and the controls. The result is discussed taking the findings of previ…

Transient features of the thalamic reticular nucleus in the human foetal brain

The architectonic organization and neuronal types of the human foetal reticular nucleus (RN)--with special reference to transient characteristics--have been investigated using antisera against calretinin, parvalbumin and neurofilament epitopes of somata and dendrites (SMI 311). The RN consists of four subdivisions (clearly distinguishable in the 6/7th gestational month): The main portion appears as a prominent structure on account of its extension and high packing density of neurons which coexpress calretinin and parvalbumin. These two calcium-binding proteins are also expressed by the perireticular nucleus forming a conspicuous grey within the internal capsule. Perireticular cells form clu…

Topical Review: Functional Anatomy of Human Hippocampal Formation and Related Structures

Data on the internal organization, and neuronal connections of the human hippocampal formation and related structures of the limbic system are briefly reviewed. In the healthy brain, somatosensory, visual, and auditory input proceeds through neocortical core and belt fields to a variety of association areas, and from here the data is transported via long cortico-cortical pathways to the extended prefrontal association cortex. Tracts generated from this highest organizational level of the brain guide the data via the frontal belt (premotor cortex) to the frontal core (primary motor area). The striatal and cerebellar loops provide the major routes for this data transfer. The main components o…

Selective bilateral blood sampling from the inferior petrosal sinus in Cushing's disease: effects of corticotropin-releasing factor and thyrotropin-releasing hormone on pituitary secretion.

We sought to enhance the sensitivity of selective bilateral blood sampling to determine adrenocorticotropin (ACTH) and prolactin levels in the inferior petrosal sinus (IPS) by administering two stimulatory agents--corticotropin-releasing factor (CRF) and thyrotropin-releasing hormone (TRH). We then determined the ACTH and prolactin levels in the IPS of 10 patients with Cushing's disease. After peripheral administration of both CRF and TRH, ACTH levels were significantly higher on the tumor side in all patients. The prolactin level was significantly higher on the tumor side when CRF or TRH was used to stimulate pituitary secretion. Postsurgical immunohistochemistry studies revealed productio…

Alterations in the organization of the isocortical layer I in trisomy 22.

The isocortical layer I of human fetal brains obtained from different cases of chromosomal abnormalities (trisomy 18, 21, 22) and controls without pathological disturbances were investigated histologically and immunohistochemically by using the antibodies SMI 311, SMI 35 and SMI 81 (SNAP 25) as well as antibodies against GAP 43 and calretinin. In cases of trisomy 22 the Cajal-Retzius cells in Nissl-sections and in SMI 311-immunopreparations do not reveal any alterations regarding their location or morphology. However, the axonal plexus, selectively labelled with SMI 35, normally located in layer Ib, is malpositioned in Ia. Likewise, SNAP 25- and GAP 43-immunoreactive structures, which were …

The nature of host tissue destruction in tumor invasion

The nature of host tissue destruction in tumor invasion was investigated in experimentally induced carcinomas and sarcomas, xenografted into skeletal muscle. By means of light and electron microscopy it was shown that in both carcinomas and sarcomas the confrontation of host tissue with the invading tumor cells does not result in immediate destruction of host tissue but in a transitory state of coexistence which gradually proceeds to progressive host tissue atrophy. This process of progressive atrophy, which finally results in the total disappearance of the invaded host tissue, is considered to be caused mainly by the increasing pressure and competitive withdrawal of oxygen and nutrients by…

Transient expression of synaptogyrin in the ganglionic eminence of the human fetal brain

Summary The ganglionic eminence (GE) representing a conspicuous bulb-like elevation of the telencephalic proliferative zone has recently been shown to be involved in the establishment of cortical connections. This study demonstrates the presence of synaptogyrin-immunoreactivity in a large number of cell bodies of the human GE between 12 and 20 weeks of gestation. From the 20 th week onwards synaptogyrin expression sharply declines. No immunoreactive structures are detectable in the 23 rd week or later. As the GE persists nearly throughout the entire fetal period these results show that its neurochemical features change distinctly in the course of development. The synaptogyrin-immunoreactive…

CT-guided stereotactic biopsy aided by Doppler ultrasonic vascular monitoring

The use of a 20 MHz pulsed Doppler technique during stereotactic brain tumour biopsies is described. By means of a miniaturized ultrasonic probe the tissue planned for biopsy was investigated for vessel signals. Out of 41 patients, with this technique a flow-pulse curve in front of the biopsy cannula was registered in 14 cases. In 9 cases one pulse curve was determined and in 5 cases two or more flow curves were found, indicating the presence of arterial vessels. The depth of the vessels signal could be localized and this area avoided for biopsy sampling. In a series of 41 stereotactic biopsies carried out in this way there was no intra-operative haemorrhage or postoperative haematoma.

Gastric α-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology

The progressive degenerative process associated with sporadic Parkinson's disease (sPD) is characterized by formation of alpha-synuclein-containing inclusion bodies in a few types of projection neurons in both the enteric and central nervous systems (ENS and CNS). In the brain, the process apparently begins in the brainstem (dorsal motor nucleus of the vagal nerve) and advances through susceptible regions of the basal mid-and forebrain until it reaches the cerebral cortex. Anatomically, all of the vulnerable brain regions are closely interconnected. Whether the pathological process begins in the brain or elsewhere in the nervous system, however, is still unknown. We therefore used immunocyt…

Distribution patterns of vimentin-immunoreactive structures in the human prosencephalon during the second half of gestation.

Neuronal migration is guided by long radially oriented glial fibres. During late stages of development radial glial cells are transformed into astrocytes. A predominant intermediate filament protein within radial glial cells and immature astrocytes is vimentin. In this study fetal brain sections were used to demonstrate the transient features of vimentin-positive radial glia. In the lower half of the cerebral wall of the 6th gestational month bundles, curvature, and crossing of vimentin-positive fibres are regularly seen. Moreover, fibres terminating on vessels are observed. In the upper half fibres are radially oriented; when ascending towards the pial surface the number and diameter of fi…

Fabry Disease With Concomitant Lewy Body Disease

AbstractAlthough Gaucher disease can be accompanied by Lewy pathology (LP) and extrapyramidal symptoms, it is unknown if LP exists in Fabry disease (FD), another progressive multisystem lysosomal storage disorder. We aimed to elucidate the distribution patterns of FD-related inclusions and LP in the brain of a 58-year-old cognitively unimpaired male FD patient suffering from predominant hypokinesia. Immunohistochemistry (CD77, α-synuclein, collagen IV) and neuropathological staging were performed on 100-µm sections. Tissue from the enteric or peripheral nervous system was unavailable. As controls, a second cognitively unimpaired 50-year-old male FD patient without LP or motor symptoms and 3…

Stage-dependent and sector-specific neuronal loss in hippocampus during Alzheimer's disease

Recent stereological studies documented a severe loss of hippocampal neurons in end-stage Alzheimer's disease. The development of the disease, however, is progressive and slow, over clinically inconspicuous decades. The Braak-staging system distinguishes six histopathological stages some of which are not accompanied by clinical symptoms. We analyzed hippocampal cell loss in correlation to Braak stages. Neuron numbers were determined with unbiased stereological principles in a defined subportion of the hippocampus of 28 subjects. There were no age-dependent neuronal losses in any of the hippocampal subdivisions examined. Compared to stage I, pyramidal cell loss in CA1 was reduced by 33% in s…

Differences in DNA Methylation Patterns and Expression of the CCRK Gene in Human and Nonhuman Primate Cortices

Changes in DNA methylation patterns during embryo development and differentiation processes are linked to the transcriptional plasticity of our genome. However, little is known about the evolutionary conservation of DNA methylation patterns and the evolutionary impact of epigenetic differences between closely related species. Here we compared the methylation patterns of CpG islands (CGIs) in the promoter regions of seven genes in humans and chimpanzees. We identified a block of CpGs in the cell cycle-related kinase (CCRK) gene that is more methylated in the adult human cortex than in the chimpanzee cortex and, in addition, it exhibits considerable intraspecific variation both in humans and …

Age-related accumulation of congophilic fibrillar inclusions in endocrine cells

Intracellular fibrillar congophilic inclusions are well known as neurofibrillary tangles in neurons and as Biondi bodies in choroid plexus epithelial cells. Recently similar amyloid-like inclusions in adrenal cortical cells were described (Eriksson and Westermark 1990). This study on 150 adrenal glands confirms these observations. In our material the age-related accumulation of congophilic inclusions starts earlier (in the sixth decade) and reaches a higher incidence (42.7%). We found similar intracellular inclusions in other endocrine organs, for example in the anterior lobe of the pituitary, in the cells of parathyroid glands and in Sertoli cells. The age-related incidence of these fibril…

Tissue characterization of benign brain tumors: Use of NMR-tissue parameters

Abstract To evaluate the potentials of NMR tissue parameters for tissue characterization we investigated 68 patients with benign brain tumors. Tissue parameters were accurately measured by a recently developed interlaced triple sequence. Each individual tumor was characterized by a set of three numbers (relaxation times T 1 and T 2 and proton density Rho). Different tumors exhibited significant overlaps of the three tissue parameters. Therefore a reliable prediction of the histological diagnosis based on the quantitative analysis of tissue parameters alone was not possible. T 2 -prolongation correlated well with water content and “regressive changes” in meningiomas and neuromas.

Changes of the ratio between myelin thickness and axon diameter in the human developing sural nerve

Axon caliber and myelin sheath thickness of individual nerve fibers were evaluated in the developing human sural nerve using three different methods of measurement: 1. ocular micrometer evaluation of large fibers, 2. photographic enlargements for evaluating large numbers of nerve fibers of all sizes, and 3. electron microscopic enlargements for more precise measurements in selected nerves. The average axonal diameter doubles from 5 months gestation to about 5 years of age. Large fiber group axons increase, during the same period, by a factor of 3--3.5 with a slight decrease thereafter. The myelin thickness increases more slowly, but continuously, between 5 months gestation until the age of …

Late-Onset Globoid Cell Leukodystrophy: Unusual Ultrastructural Pathology and Subtotal β-Galactocerebrosidase Deficiency

An 11-year-old girl was found to have severely reduced β-galactocerebrosidase activity as evidence of late-onset globoid cell leukodystrophy, while her mother had almost normal enzyme activity in circulating white blood cells. Clinically, the patient showed a remitting course marked by seizures, ataxia, white-matter disease on computed tomographic scan, and reduced conduction velocities of peripheral nerves. Symptoms improved somewhat around the age of 10 years. Two sural nerve biopsies, performed 6 years apart, disclosed a demyelinating neuropathy. By electron microscopy, membrane-bound vacuolar lysosomes in Schwann cells of myelinated axons, unlike the typical needlelike inclusions seen …

Image Analysis of Proliferating Cells in Tumors of the Human Nervous System

Obtaining growth fractions from immunohistological preparations by the commonly used cell count calculation method is time consuming. For the first time, we investigated and compared the detection of proliferating cells in immunohistologically labeled tissue from tumors of the nervous system using the monoclonal antibody Ki-67 by a new computerized image analysis system and by cell count calculation. The two methods showed a high correlation (correlation index, 0.98) in 37 gliomas (2 pilocytic astrocytomas, 10 Grade II astrocytomas, 5 Grade III astrocytomas, 20 Grade IV astrocytomas and glioblastoma multiforme) and a heterogenous group of 10 additional tumors of the nervous system, includin…

Changes of the ratio between myelin thickness and axon diameter in human developing sural, femoral, ulnar, facial, and trochlear nerves

Previous studies on sural nerves were extended to human femoral, ulnar, facial and trochlear nerves. As asynchronous development of axon diameter and myelin sheath thickness was noted in all nerves studied. Whereas axons reach their maximal diameter by or before 5 years of age, maximal myelin sheath thickness is not attained before 16-17 years of age, i.e., more than 10 years later. The slope of the regression lines for the ratio between axon diameter and myelin thickness is significantly steeper in older than in younger individuals; it also differs if small and large fibers with more or less than 50 myelin lamellae are evaluated separately. The number of Schmidt-Lanterman incisures during …

Anomalous alterations affecting microglia in the central nervous system of a fetus at 12 weeks of gestation: case report.

We report here on the first documented case of profound alterations specifically affecting the microglial population within the nervous system during the fetal period. This case, derived at gestational week 12, was one amongst a series of second trimester brains currently being investigated with respect to microglial colonization of the human fetal brain. No significant pathological alterations could be identified upon gross macroscopy or following microscopic analysis of serial brain sections stained with cresyl fast violet (Nissl). By contrast, sections stained immunohistochemically to detect MHC class II (CR3/43) and CD68 (PG-M1) antigens revealed a marked pathological change in the morp…

Allocortical neurofibrillary changes in progressive supranuclear palsy.

Silver techniques for intraneuronal cytoskeleton abnormalities (neurofibrillary tangles and neuropil threads) and extracellular A4-amyloid deposits were used to examine lesions of the cerebral cortex in six cases of progressive supranuclear palsy (three were mentally unimpaired and three showed moderate degrees of dementia). Deposits of A4-amyloid protein occurred in small numbers or were absent. Neurofibrillary tangles and neuropil threads were present in all cases and were largely confined to the allocortex. A characteristic pattern of changes was found in the entorhinal cortex. The three mentally unimpaired individuals had mild cortical changes virtually confined to the transentorhinal r…

Apolipoprotein E polymorphism is associated with both senile plaque load and Alzheimer-type neurofibrillary tangle formation.

Recent work provided evidence that the apolipoprotein (apo) E polymorphism is associated with late-onset sporadic Alzheimer's disease. The major histological hallmarks of Alzheimer's disease are the extraneuronal deposition of A4/beta-amyloid and the intraneuronal formation of neurofibrillary tangles, the latter correlating strongly with the psychometric status. We examined the relationship between the apo E polymorphism and Alzheimer's disease-related histological changes using a staging system which accounts for the progression of the disease over time and correlates well with the cognitive decline ante mortem. We observed a significant positive correlation between both neurofibrillary ch…

Senile amyloidosis: Principles of localization in a heterogeneous form of amyloidosis

In order to identify amyloid deposits in patients over 60 years of age (so-called senile amyloid), the following five tissues were investigated under the light and electron microscope : 1. pituitary gland, 2. pancreatic islets of Langerhans, 3. heart, 4. aorta, and 5. brain. In all an increasing incidence of amyloid deposits was found with increasing age, and in the brain a significant quantitative increase in amyloid deposits with increasing age was observed. Despite the biochemical heterogeneity of amyloid found in old age, all the deposits seen in tissues examined were morphologically similar. Typical amyloid fibrils were always found (diameter 60–100 A), and these were invariably deposi…

Szintigraphie adrenerger Tumoren mit 131J-meta-Benzylguanidin

Pheochromocytoma scanning using 131J-meta-benzylguanidine was done in one patient with metastasizing paraganglioma, one patient with multiple endocrine neoplasia type IIb. No activity of tumour tissue could be demonstrated in the patient with metastasizing paraganglioma, whereas the pheochromocytoma could be clearly defined in the patient with multiple endocrine neoplasia type IIa. The female with multiple endocrine neoplasia type IIb showed a suspect space-occupying lesion of the left adrenal using computed tomography. Pheochromocytoma could be excluded by 131J-benzylguanidine scanning, selective estimation of catecholamines in adrenal venous blood as well as the glucagon stimulation and c…

Stanley Fahn Lecture 2005: The staging procedure for the inclusion body pathology associated with sporadic Parkinson's disease reconsidered.

The synucleinopathy known as sporadic Parkinson's disease (PD) is a multisystem disorder that severely damages predisposed nerve cell types in circumscribed regions of the human nervous system. A recent staging procedure for the inclusion body pathology associated with PD proposes that, in the brain, the pathological process (formation of proteinaceous intraneuronal Lewy bodies and Lewy neurites) begins at two sites and continues in a topographically predictable sequence in six stages, during which components of the olfactory, autonomic, limbic, and somatomotor systems become progressively involved. In stages 1 to 2, the Lewy body pathology is confined to the medulla oblongata/pontine tegme…

Amyloidoma of the gasserian ganglion as a cause of symptomatic neuralgia of the trigeminal nerve: report of three cases.

Three cases of symptomatic neuralgia of the trigeminal nerve due to an amyloidoma in the gasserian ganglion are described. The correct diagnosis was not made prior to histological examination of the surgical biopsy specimens. Medical history and clinical observation led to the diagnosis of a malignant process of the nasal cavities in the first patient; of an inflammatory dental focus in the second patient; and of multiple sclerosis in the third patient. CT findings were normal in cases 1 and 2; in case 3, a schwannoma was suspected from the CT appearances. In case 1, MRI had not been performed; in cases 2 and 3, MRI revealed a tumour mass which was also considered to be a schwannoma. Histol…

Apolipoprotein E polymorphism influences not only cerebral senile plaque load but also Alzheimer-type neurofibrillary tangle formation.

Only recently, evidence was provided that apolipoprotein E allele epsilon 4 located on Chromosome 19 is associated with late onset (i.e. senile) sporadic Alzheimer's disease. Histologically, Alzheimer's disease is associated with intraneuronal neurofibrillary changes and extraneuronal A4/beta-amyloid deposition. We set out with a histological staging system which considers the gradual development of Alzheimer's disease-related histological changes over time and correlates highly with the cognitive decline ante mortem. Our analysis revealed that both the mean stage for A4/beta-amyloid deposits and the mean stage for neurofibrillary tangles get significantly shifted upwards in epsilon 4-carri…

Alzheimer's disease: Amyloid deposits in the cerebellar cortex

ALTERED RATIO BETWEEN AXON CALIBER AND MYELIN THICKNESS IN SURAL NERVES OF CHILDREN

ABSTRACT Maturation of myelin sheaths in normal sural nerves of children proceeds more slowly than axon growth. This asynchronous development of axons and myelin sheaths results in a statistically significant change of the ratio between axon caliber and myelin thickness during normal development. Therefore, myelin thickness of individual nerve fibers must be related to the size of the axons as well as to the age of the individuals studied. Abnormalities of the relationship between myelin thickness and axon diameter (primary hypomyelination of large, or small, or all fibers) were clearly identified in cases with metachromatic leukodystrophy, KRABBE's, DEJERINE-SOTTAS’, COCKAYNE'S and SANFILI…

Prions, mad cow disease, and preventive measures: a critical appraisal

In 1996 the first key epidemiological study on bovine spongiform encephalitis (BSE) appeared in the renowned journal Nature [1]. In that article it was estimated that by the year 1996, some 750,000 cows with BSE had entered the food chain in Great Britain. Accordingly, millions of people in GB must have consumed contaminated meat. That same year the first report on a new form of Creutzfeldt-Jakob disease [variant (v) CJD] manifesting in young patients appeared [26]. A connection between this disease and BSE was assumed. In view of the suspicion that the use of meat and bone meal (MBM) had led to the outbreak of BSE, feeding with MBM was banned in the year 1988. The number of new BSE infecti…

Immunohistochemical investigation of the brain of aged dogs. I. Detection of neurofibrillary tangles and of 4-hydroxynonenal protein, an oxidative damage product, in senile plaques.

In the aging dog brain lesions develop spontaneously. They share some morphological characteristics with those of Alzheimer 's disease in man. Diffuse and primitive plaques are well known, whereas neuritic plaques rarely develop. Neurofibrillary tangles have not been seen in the canine. The aim of the present investigation was to study major age-related changes of the dog's brain using paraffin sections with respect to cross-immunoreactivity of tau, A beta protein and other immunoreactive components including hydroxynonenal protein, which is a marker for oxidative damage. The occurrence of neurofibrillary tangles and of the protein tau therein was studied in serial brain sections of two dog…

Alzheimer-related changes in the presubicular region

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 lar…