Biomedical subjects

E Braak

Publications and source records attributed to E Braak.

At least 55 records · Page 3Linked to original sources

PubMed1997

Cytoskeletal alterations in the aged human neurohypophysis.

The hypophyses of 24 individuals, aged 79-89 years (mean age 83.5+/-3.3 years), were investigated for cytoskeletal changes associated with abnormally phosphorylated tau protein using the monoclonal antibodies AT8, PHF-1 and Alz-50. A previously unreported pattern of cytoskeletal changes was identified in the neurohypophysis consisting of axon-like fibers and large swellings resembling Herring bodies. The density of the cytoskeletal lesions was subject to notable variation among individuals. Marked neurohypophyseal alterations were also noted in cases even devoid of Alzheimer's disease-related cytoskeletal pathology in neocortical areas. Fully developed Alzheimer's disease is thus not a prerequisite for the presence of advanced neurohypophyseal alterations. In conclusion, the aged human neurohypophysis is revealed as a potential focus of abnormal cytoskeletal changes which may impair the neuroendocrine function of the hypothalamo-neurohypophyseal system.

Aged↗

PubMed1997

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 themselves not sufficient to produce overt intellectual deterioration. Fully developed Parkinson's disease with concurring incipient Alzheimer's disease is likely to cause impaired cognition.

Dementia↗

PubMed1997

Alzheimer's disease: transiently developing dendritic changes in pyramidal cells of sector CA1 of the Ammon's horn.

In the course of Alzheimer's disease, specific CA1 pyramidal cells develop dendritic changes, which can only be observed transiently. Distal segments of the apical dendrite running through the stratum lacunosum-moleculare show spindle-shaped dilations filled with abnormal tau protein. The alteration eventually leads to amputation of the changed segment. The damage first appears at stage II in the evolution of the neurofibrillary changes [5], is best developed at stage III, and vanishes from the tissue at stage IV. It is usually not observed in stages V and VI (fully developed Alzheimer's disease).

Adult↗

PubMed1997

Neurofibrillary pathology in the human paraventricular and supraoptic nuclei.

Severe neurofibrillary changes were identified in the paraventricular and supraoptic nuclei of elderly individuals using markers for Alzheimer's disease-related intraneuronal pathology. This neurofibrillary pathology is remarkable in that the magnocellular paraventricular and supraoptic nuclei are particularly resistant to Alzheimer's disease. Moreover, the changes were observed even in non-demented controls, indicating that they develop independently of Alzheimer's disease. The alterations in the paraventricular and supraoptic nuclei were consistently accompanied by neurofibrillary changes in the mediobasal hypothalamus.

Aged↗

PubMed1997

Distribution, levels, and activity of glycogen synthase kinase-3 in the Alzheimer disease brain.

A number of studies have implicated a proline-directed protein kinase, glycogen synthase kinase-3 (GSK-3) in the hyperphosphorylation of tau in Alzheimer's disease (AD). Toward understanding the role of GSK-3 in the abnormal hyperphosphorylation of tau in AD we have found that GSK-3 is prominently present in neuronal cell bodies and their processes and co-localizes with neurofibrillary changes in AD brain. Furthermore, the levels of GSK-3 as determined by indirect ELISA are approximately 50% increased in the postsynaptosomal supernatant from AD brains as compared to the controls. However, no increase in GSK-3 enzyme activity was detected. In AD brain, with its reduced phosphatase activity, even normal levels of GSK-3 activity might be sufficient for the hyperphosphorylation of tau.

Alzheimer Disease↗

PubMed1997

Staging of Alzheimer-related cortical destruction.

Currently used criteria for neuropathological diagnosis of Alzheimer's disease (AD) allow only the distinction of fully developed AD or ill-defined cases with less severe pathologic alterations. There is a need for a staging procedure that is able to supplement the currently used criteria, to allow for sufficient differentiation between the initial and intermediate stages of the illness, and to provide a characterization of the degree of involvement in the brain tissue of "nondemented, age-related controls." The destructive process underlying AD is characterized by a typical distribution pattern of brain changes that is specific with respect to area, lamina, and even cell type. The most conspicuous change is the progressive deposition of abnormal proteins, both between and within the nerve cells. Conventional staining methods to identify these deposits lack sensitivity and specificity. Silver methods (specifically the Gallyas silver-iodide technique for neurofibrillary changes and the Campbell-Switzer silver-pyridin technique for brain amyloid) are by far the best suited to diagnostic work. They are inexpensive, simple to use, and far more reliable. This article describes the patterns of staining typically found with each of these techniques in the brains of patients with progressively severe AD and describes how the specific changes observed can be used as a staging system for diagnostic purposes.

Aged↗

PubMed1996

A sex difference in neurodegeneration of the human hypothalamus.

The mediobasal hypothalamus (MBH) of 33 males (mean age, 77 +/- 10 years) and 31 females (mean age, 78 +/- 10.3 years) was investigated for neurofibrillary pathology associated with abnormally phosphorylated tau protein. A conspicuous pathology was identified, characterized by terminal-like processes contacting the neurohemal vasculature of the posterior median eminence and the adjacent infundibular nucleus. This pathology revealed a striking sex difference: it was identified in 79% of the males, but observed in only 6% of the females. The vessel-associated neurofibrillary lesions of the mediobasal hypothalamus develop independently of Alzheimer's disease (AD)-related neocortical pathology. The sex-dependent neurofibrillary degeneration is suggested as an explanation for an impairment in neuroendocrine function previously reported in elderly men.

Aged↗

PubMed1996

Age, neurofibrillary changes, A beta-amyloid and the onset of Alzheimer's disease.

Intraneuronal neurofibrillary changes and extracellular A beta-amyloid deposits are neuropathologic hallmarks of Alzheimer's disease. Examination of numerous non-selected autopsy cases demonstrates that they are by no means normal concomitants of brain aging. Rather, the initial neurofibrillary changes indicate the beginning of Alzheimer's disease. A small proportion of cases displays particularly early development of the intraneuronal changes, indicating that advanced age is not a prerequisite for the evolution of the lesions. However, the mean of stages in the development of the specific neurofibrillary pathology increases with age. Alzheimer's disease is thus an age-related, not an age-dependent disease.

Adult↗

PubMed1996

New aspects of pathology in Parkinson's disease with concomitant incipient Alzheimer's disease.

Alzheimer's disease and Parkinson's disease 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 Alzheimer's disease, susceptible neurons produce neurofibrillary tangles and neuropil threads, while in Parkinson's disease, they develop Lewy bodies and Lewy neurites. The specific lesional pattern of both illnesses accrues slowly over time. Presently available data support the view that fully developed Parkinson's disease with concurring incipient Alzheimer's disease is likely to cause impaired cognition.

Alzheimer Disease↗

PubMed1996

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 neurofibrillary changes spread across the cerebral cortex. The pathologic process commences in the transentorhinal region (clinically silent stages I and II), then proceeds into adjoining cortical and subcortical components of the limbic system (stages III and IV - incipient AD), and eventually extends into association areas of the neocortex (stages V and VI - fully developed AD). During the course of PD, important components of the limbic system undergo specific lesions as well. The predilection sites include the entorhinal region, the CA2-sector of the hippocampal formation, the limbic nuclei of the thalamus, anterior cingulate areas, agranular insular cortex (layer VI), and - within the amygdala - the accessory cortical nucleus, the ventromedial divisions both of the basal and accessory basal nuclei, and the central nucleus. The amygdala not only generates important projections to the prefrontal association areas but also exerts influence upon all non-thalamic nuclei which in a non-specific manner project upon the cerebral cortex and upon the nuclei regulating endocrine and autonomic functions. All these amygdala-dependent structures themselves exhibit severe PD-specific lesions. In general, the extranigral destructions are in themselves not sufficient to produce overt intellectual deterioration. Similarly, AD-related pathology up to stage III may be asymptomatic as well. Fully developed PD with concurring incipient AD, however, is likely to cause impaired cognition. Presently available data support the view that the occurrence of additional lesions in the form of AD stage III (or more) destruction is the most common cause of intellectual decline in PD.

Aging↗

PubMed1996

Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis.

The pattern of neurofibrillary changes which gradually develops in the course of Alzheimer's disease bears a striking resemblance to the inverse sequence of cortical myelination. Factors released by oligodendrocytes exert a strong influence upon nerve cells and suppress disordered neuritic outgrowth. It is suggested that the lack of such factors due to premature dysfunction of oligodendrocytes leads to alterations of the neuronal cytoskeleton and eventually to the appearance of Alzheimer-type neurofibrillary changes.

Alzheimer Disease↗

PubMed1996

Evolution of the neuropathology of Alzheimer's disease.

Our knowledge of the etiology and pathogenesis of Alzheimer's disease is limited. The most conspicuous changes seen in the brain are deposits of insoluble proteins in both extracellular and intraneuronal locations. The extracellular deposits consist primarily of a specific A4 amyloid protein. The significance of these deposits remains to be determined, as they are often found in the cerebral cortex of non-demented elderly persons. More telling is the gradual accumulation of insoluble fibrous material within some neurons that consists mainly of abnormally phosphorylated tau protein. Six stages of increasingly severe cortical destruction can be distinguished. Stages I and II are characterized by neurofibrillary changes that are largely confined to the transentorhinal region, whereas stages III and IV are marked by severe involvement of both the entorhinal and transentorhinal regions. Isocortical destruction occurs during stages V and VI. This progression in cortical pathology correlates with the gradual worsening of clinical symptoms.

Alzheimer Disease↗

PubMed1996

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 corticocortical pathways to the extended prefrontal association cortex. Tracts generated from this highest organization 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 of the limbic system (the hippocampal formation, the entorhinal region, and the amygdala) maintain a strategic position between the sensory and the motor association areas. Part of the stream of data from the sensory association areas to the prefrontal cortex branches off and eventually converges on the entorhinal region and the amygdala, These connections establish the afferent leg of the limbic loop. In addition, the limbic centers receive substantial input from nuclei processing viscerosensory information. The entorhinal region, the hippocampal formation, and the amygdala are densely interconnected. Important among these connections is the perforant path, which originates in the entorhinal cortex and projects to the hippocampal formation (fascia dentata, Ammon's horn, and subiculum). The subiculum projects to the amygdala, entorhinal region, mamillary nuclei, and anterior and midline thalamic nuclei. The hippocampal formation, the entorhinal region, and the amygdala generate the efferent leg of the limbic loop, which is directed toward the prefrontal cortex. Additional projections reach the key nuclei that control endocrine and autonomic functions. Furthermore, the amygdala exerts influence on all nonthalamic nuclei projecting in a nonspecific manner to the cerebral cortex (ie, the cholinergic magnocellular forebrain nuclei, the histaminergic tuberomamillary nucleus, the dopaminergic nuclei of the ventral tegmentum, the serotonergic anterior raphe nuclei, and the noradrenergic locus ceruleus). The limbic loop centers thus are in the unique strategic position to perform integration of exteroceptive sensory data of various sources with interoceptive stimuli from autonomic centers. Their efferent projections exert influence on both the prefrontal association cortex and the key centers controlling endocrine and autonomic functions.

Hippocampus↗

PubMed1995

Nigral and extranigral pathology in Parkinson's disease.

This article reviews data on the internal organization, neuronal types, and interconnections of limbic and motor components of the human brain, and the specific lesions which a few of them undergo during the course of Parkinson's disease (neuronal loss associated with the development of Lewy bodies and Lewy neurites). The severe involvement of nigral neuromelanin-laden projection cells has received particular attention during the past decades. This lesion interferes with normal function of the striatum and probably contributes to many of the motor dysfunctions characteristically occurring in Parkinson's disease. The similarly severe involvement of several areas and nuclei outside of the substantia nigra has often escaped notice. However, the pathology of Parkinson's disease cannot be completely described unless changes in these extranigral areas are taken into account. Interpretation of the characteristic lesional pattern is facilitated by combining schemata of both the limbic and motor systems. This approach reveals a key role by the amygdala and related structures in extranigral pathology. Severe lesions occur in the central amygdaloid nucleus, in nuclei projecting to the cerebral cortex in a non-specific manner, and in nuclei regulating endocrine and autonomic functions. It is suggested that extranigral lesions contribute to the development of behavioral changes and autonomic dysfunction.

Amygdala↗

PubMed1994

Abnormally phosphorylated tau protein related to the formation of neurofibrillary tangles and neuropil threads in the cerebral cortex of sheep and goat.

Frontal sections including temporal isocortex, entorhinal region and hippocampus from aged domestic animals (dog, cat, horse, sheep and goat) were studied for Alzheimer-related changes using immunostaining with the AT8 antibody for abnormally phosphorylated tau protein and selective silver techniques for A4 amyloid and neurofibrillary changes of the Alzheimer type. The material available to us did not show A4 amyloid deposits or argyrophilic neurofibrillary changes. Only the brains of aged sheep and goat exhibited the presence of AT8-immunoreactive pyramidal cells in the entorhinal region and hippocampal formation. Two groups of AT8-positive neurons could be observed: The first group contained evenly distributed immunoreactive material in all parts of the soma, the dendrites and the axon. The neuronal processes appeared quite normal. The second group, however, showed conspicuous changes in the cellular processes consisting of a loss of immunoreactivity within the axon and the proximal dendrites and the appearance of intensely stained swellings within the curved distal dendrites. These changes were closely reminiscent to alterations of the cytoskeleton known to occur at the same location in the aging human brain and in Alzheimer's disease. The findings justify a closer look at sheep and goat when searching for suitable animal models for experimental studies of the conditions responsible for the development of Alzheimer-related neurofibrillary changes.

Animals↗

PubMed1994

A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads.

Frontal sections of the temporal lobe including the transentorhinal/entorhinal region, amygdala, and/or hippocampus from human adult brains are studied for cytoskeleton changes using immunostaining with the antibodies AT8 and Alz-50 and selective silver impregnation methods for neurofibrillary changes of the Alzheimer type. For the purpose of correlation, the two methods are carried out one after the other on the same section. Layer pre-alpha in the transentorhinal/entorhinal region harbours nerve cells which are among the first nerve cells in the entire brain to show the development of neurofibrillary changes. This presents the opportunity for study of both early events in the destruction of the cytoskeleton in individual neurons, and to relate changes which occur in the neuronal processes in the absence of alterations in their immediate surroundings to those happening in the soma. Immunoreactions with the AT8 antibody in particular reveal a clear sequence of changes in the neuronal cytoskeleton. Group 1 neurons present initial cytoskeleton changes in that the soma, dendrites, and axon are completely marked by granular AT8 immunoreactive material. These neurons appear quite normal and turn out to be devoid of argyrophilic material when observed in silver-stained sections. Group 2 neurons show changes in the cellular processes. The terminal tuft of the apical dendrite is replaced by tortuous varicose fibres and coarse granules. The distal portions of the dendrites are curved and show appendages and thickened portions. Intensely homogeneously immunostained rod-like inclusions are encountered in these thickened portions and in the soma. A number of these rod-like inclusions are visible after silver staining, as well. Group 3 neurons display even more pronounced alterations of their distal--most dendritic portions. The intermediate dendritic parts lose immunoreactivity, but the soma is homogeneously immunostained. Silver staining reveals in most of the distal dendritic parts neuropil threads, and in the soma a classic neurofibrillary tangle. Group 4 structures are marked by accumulations of coarse AT8-immunoreactive granules. Silver staining provides evidence that the fibrillary material has become an extraneuronal, "early" ghost tangle. Finally, group 5 structures present "late" ghost tangles in silver-stained sections but fail to demonstrate AT8 immunoreactivity. It is suggested that the altered tau protein shown by the antibody AT8 represents an early cytoskeleton change which eventually leads to the formation of argyrophilic neurofibrillary tangles and neuropil threads.

Adult↗

PubMed1994

Amygdala pathology in Parkinson's disease.

The amygdala undergoes severe pathological changes during the course of Parkinson's disease (PD). Lewy bodies and Lewy neurites are distributed in a specific manner throughout the nuclear complex. The lesional pattern displays only minor interindividual variation. The most prominent changes occur in the accessory cortical and central nuclei. The cortical, accessory basal and granular nuclei show less severe alterations, while the basal and lateral nuclei, as well as the intercalated cell masses, generally remain uninvolved. The amygdala receives a broad range of afferents, allowing integration of exteroceptive information with interoceptive data. It generates major projections to the isocortex (the prefrontal cortex in particular), limbic system (hippocampus and entorhinal region) and centers regulating endocrine and autonomic functions. The specific lesional pattern seen in PD destroys part of the nuclear gray matter and its connections and, thus, may likely contribute to the development of behavioral changes and autonomic dysfunctions.

Aged↗

PubMed1993

The new monodendritic neuronal type within the adult human cerebellar granule cell layer shows calretinin-immunoreactivity.

The distribution of calretinin immunoreactive structures within the granule cell layer of the adult human cerebellar cortex was studied using the avidin-biotin peroxidase method. Immunoreactivity is found in numerous fibers and glomerular formations, in Golgi- and Lugaro cells as well as in a recently described novel neuronal type, the monodendritic cell. The soma of the monodendritic neuron contains a faintly stained nucleus and issues a single short dendrite terminating in a tuft. Most probably, the tuft contributes to the formation of a glomerulum. Soma and tuft are of about the same size (diameter 10-18 microns). The number of monodendritic neurons is higher in the vermal than in the hemispheric part of the lobulus (lobulus VII) and is higher in lobulus X than in lobulus VII of the vermis.

Adult↗