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H Braak

Publications and source records attributed to H Braak.

At least 91 records · Page 5Linked to original sources
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

Pigment variant of neuronal ceroid-lipofuscinosis.

A 6-year-old girl had progressive ataxia, and visual disturbances resulting in blindness. She died in her sleep at age 22 years. She shared with her sister and paternal relatives bilateral pes cavus deformities and impaired deep-tendon reflexes which suggested Charcot-Marie-Tooth disease. Her sister, who also had both polyneuropathy and a progressive central nervous system (CNS) disease, did not have pigmentary retinopathy. At autopsy, the patient was found to have neuronal ceroid-lipofuscinosis (NCL) marked by intraneuronal accumulation of autofluorescent granular lipopigments in ballooned perikarya and conspicuous extraneuronal pigmentation of subcortical grey matter, but without axonal spheroids. These findings indicate a pigment variant of NCL and represent one of very few patients recorded. The ultrastructure of the intraneuronal pigments was uniformly granular, while that of the extraneuronal pigments found within processes of the neuropil and glial perikarya was more variegated. In addition to those patients with the pigment variant of NCL, described earlier by Jakob and Kolkmann [1973: Acta Neuropathol (Berl) 26:225-236], and Jervis and Pullarkat [1978: Neurology 28:500-503], our patient shared clinical symptoms with those described in a family afflicted with polyneuropathy and NCL by Wisniewski et al. [1987: J Child Neurol 2:33-41]. Currently, it is unclear whether they have similar atypical forms of juvenile NCL (JNCL). We conclude that the spectrum of pigment variants in lysosomal diseases is heterogeneous: only few and recently described patients have had NCL, while others most likely had other forms of lipidosis.

Cerebral Cortex↗
PubMed1995

Close-meshed prevalence rates of different stages as a tool to uncover the rate of Alzheimer's disease-related neurofibrillary changes.

The speed of progression of Alzheimer's disease-related neurofibrillary changes is unknown. One reason for this is the impossibility to histopathologically follow-up one and the same individual over decades of their life. The present approach takes advantage of a recently introduced classification system which allows for a ranking of Alzheimer's disease-related neurofibrillary changes into six stages [Braak and Braak Acta Neuropath (1991) 82, 239-259] and analyses a staged sample of 887 brains obtained from routine autopsy. It sets out to interpret these cross-sectional data in dynamic longitudinal terms, in order to estimate the rate of passing through the various stages. The time needed to attain respective stages of pathology for 5% of a given cumulative sample is determined. The resulting fifth centiles are a measure of the average rate by which the disease-related changes progress assuming that the underlying stages represent a sequence of events and do not independently emerge. Advancing age and the prevalence of Alzheimer's disease-related changes of a given stage show a nonlinear positive correlation with only slight acceleration above the age of 65 years. Statistically, it takes at least 16 years from stage I to stage II, about 14 years pass by from stage II to III, 13 years from stage III to IV and five years from stage IV to V (= Alzheimer's disease) for 5% of a given cumulative sample. Thus, the deep roots of Alzheimer's disease-related neurofibrillary changes can be traced about 50 years back and may even extend into adolescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
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↗
PubMed1994

Pathological changes of the retrosplenial cortex in senile dementia of Alzheimer type.

Six brains of patients aged from 71 to 85 years of clinically and pathologically diagnosed senile dementia of Alzheimer type and six brains of age-matched controls (55-91 years) was used for this study. The retrosplenial cortex of these brains have been examined by Gallyas and Campbell-silver impregnations. Gallyas preparation showed a number of intracellular pathological changes in retrosplenial cortex of demented individuals. Although the neuritic plaques, the neurofibrillary tangles and neuropil threads were seen in all lamina, their high density appear in lamina IIIa and V of retrosplenialis lateralis (Rsl), retrosplenialis intermedia (Rsi), retrosplenialis media (Rsm) and parasplenialis (Ps). The retrosplenial cortex of non-demented individuals was almost devoid of neurofibrillary changes. The retrosplenial cortex of all demented individuals and one age-matched controls showed a large amount of amyloid deposits in Campbell preparation, while two non-demented individuals showed only small amounts of amyloid. The amyloid deposition can be classified into three types. The packing of Campbell-argyrophilic material show area-specific and lamina-specific distribution.

Aged↗
PubMed1993

Neuropathological staging of Alzheimer lesions and intellectual status in Alzheimer's and Parkinson's disease patients.

In both Alzheimer's disease (AD) and Parkinson's disease (PD), neurofibrillary tangles (NFT), in contrast to amyloid deposits, show a hierarchical spreading pattern from the allocortex to isocortical association areas with early involvement of the entorhinal region, a major relay station between hippocampus and isocortex. Based on the distribution pattern of NFT in human brain, a neuropathological staging of neuritic AD pathology has been proposed. Comparative studies of this neuropathological staging of neuritic AD changes with psychometrically assessed intellectual status (mini-mental state) in prospective cohorts of 29 aged individuals and 28 PD patients showed a linear correlation of morphological AD staging with the psychostatus in both disorders. The pattern of neuronal degeneration associated with neuritic AD pathology in both AD and PD may be an important basis of cognitive decline in both disorders.

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↗
PubMed1993

Parvalbumin-immunoreactive structures of the adult human entorhinal and transentorhinal region.

Parvalbumin-immunoreactive structures in the entorhinal and transentorhinal region of the adult human brain were studied using the avidin-biotin-peroxidase technique. Parvalbumin-immunoreactive neurons and fibers (axons) were present in all layers (layer nomenclature according to Rose, 1927). The density of fibers was high in the islands of the superficial cell layer pre-alpha and in layer pre-beta and still heavier in pre-gamma. In the subjacent lamina dissecans it diminished abruptly and remained low in all layers of the internal principal stratum (layers pri-alpha, -beta, -gamma). This low density of fibers facilitated recognition of axon cartridges in layers pri-alpha and pri-gamma. Axon cartridges were also present within layers pre-beta and pre-gamma but were obscured by the dense fiber network there. Parvalbumin immunoreactivity was observed in the nerve cell soma and throughout the dendritic tree allowing the distinction of numerous nerve cell types. All parvalbumin-immunoreactive neurons belonged to the class of nonpyramidal neurons. Their lipofuscin pigment patterns differed distinctly from that of the pyramidal and modified pyramidal neurons. Based on their location, soma size, and dendritic arborization, they were grouped as large, medium-sized, and small neurons either of the multipolar or bipolar (vertical or horizontal) type. One type could be identified as an axo-axonic neuron, more specifically as a chandelier neuron generating axon cartridges. The dense fiber net within layer pre-gamma suggested the existence of another neuronal type, probably a neuron with an extended axonal ramification. The identified neurons were compared to neuronal types described in the literature from Golgi studies.

Adult↗
PubMed1993

Staging of Alzheimer-related cortical destruction.

The gradual intraneuronal accumulation of an insoluble fibrous material which partly consists of abnormally phosphorylated tau protein (neurofibrillary change) represents an important neuropathological hallmark of Alzheimer's disease. Neurofibrillary tangles and neuropil threads formed from this material develop in only a few types of cortical pyramidal cells. The first changes are seen in the entorhinal cortex. The destructive process then spreads into the hippocampal formation and eventually encroaches upon the isocortex. This sequence of events permits the distinction of six stages with a progressive increase in the severity of cortical destruction. The entorhinal region serves as an important interface between the isocortex and hippocampus. This interface function is markedly impaired due to the early deterioration of the entorhinal cortex. Severe entorhinal involvement is considered to represent the morphological counterpart of clinically incipient Alzheimer's disease. Similar changes are found in mentally impaired individuals suffering from Parkinson's disease or progressive supranuclear palsy.

Aged↗