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H Braak

Publications and source records attributed to H Braak.

At least 73 records · Page 4Linked to original sources
PubMed1998

Pick's disease: cytoskeletal changes in the hypothalamic lateral tuberal nucleus.

Basolateral portions of the human hypothalamus contain an extended nuclear gray, the lateral tuberal nucleus (LTN), which undergoes conspicuous pathological changes in a number of neurodegenerative diseases. The present study points to the severe affliction of this nucleus in Pick's disease (PID). Immunoreactions for abnormally phosphorylated tau-protein permit identification of the permutations. Only a fraction of the abnormal fibrillary material developing in the course of the disease shows a pronounced argyrophilia. Key features are the Pick bodies (PBs) which contain an argyrophilic material. Unusual non-spherical PBs develop in the LTN as flat structures with peripheral indentations. Small teardrop-like Pick neurites (PNs) emerge in varicose widenings of neuronal processes and display a much weaker argyrophilia. The characteristic alterations seen in PID reliably can be differentiated from lesions of the LTN which slowly emerge in the course of Alzheimer's disease (AD).

Aged↗
PubMed1998

Improved method facilitates reliable APOE genotyping of genomic DNA extracted from formaldehyde-fixed pathology specimens.

Apolipoprotein E (APOE) genotyping of genomic DNA extracted from formaldehyde-fixed specimens is cumbersome: there is not only a low yield or failure of PCR amplification (presumably due to degradation of DNA in the formaldehyde-fixed and paraffin-embedded tissue), but the standard method also involves the separation of DNA fragments as small as 48, 72, 81 and 91 bp requiring high-yield PCR products. Here we report about a semi-nested PCR method suitable for providing specific high-yield PCR products from DNA that has been extracted from formaldehyde-fixed specimens which initially generate low-quality templates. This method facilitates reliable APOE genotyping of DNA from difficult templates.

Apolipoproteins E↗
PubMed1998

High frequency of apolipoprotein E epsilon4 allele in young individuals with very mild Alzheimer's disease-related neurofibrillary changes.

The pathological process of initial neurofibrillary (NF) changes underlying Alzheimer's disease (AD) represents the early preclinical phase of the disease. In a small percentage of individuals, these initial NF changes (Braaks' stage I of six stages) may develop at a surprisingly young age. The aim of this study was to determine the impact of apolipoprotein E (ApoE) on the development of such initial NF changes in young individuals. To this end, the ApoE genotypes were determined using a seminested polymerase chain reaction assay followed by restriction isotyping in young individuals (n = 44; mean age of 38 years) with initial NF changes (stage I). The results were compared with ApoE genotypes of age-matched controls (n = 70) devoid of such changes (stage 0). Stage I cases exhibited a significantly higher epsilon4 allele frequency compared to controls (0.18 vs 0.09, P = 0.039). Thus, the present study reveals an association of epsilon4 allele with the early onset of AD-related NF changes in young individuals. This finding underlines the relevance of the asymptomatic phase in the course of AD.

Adolescent↗
PubMed1998

Involvement of precerebellar nuclei in Pick's disease.

Pick's disease is a progressive degenerative disorder of the human brain which involves not only numerous areas of the cerebral cortex but also a characteristic set of subcortical nuclei. The disorder is associated with the formation of abnormal and hyperphosphorylated tau protein, which occurs in only a few susceptible neuronal types and leads to major cytoskeletal alterations. Preferentially affected by the destructive process are small nerve cells of both cortical areas and subcortical nuclei. Immunoreactions for abnormally phosphorylated tau protein permit identification of the alterations in their entirety. In an initial step in their development, patches of a nonargyrophilic material appear, irregularly filling both the somata and neurites of afflicted cells. The abnormal material is then partially converted into condensed spindle-shaped or spherical structures, which gradually become significantly argyrophilic. Globose argyrophilic Pick bodies eventually appear within the somata, and small Pick neurites of variable sizes and shapes develop in varicose expansions of the dendritic processes. Silver staining reveals only a fraction of the abnormal material and is adequate only for diagnostic purposes, while immunostaining of the abnormal tau protein discloses the complete neuropathological picture. The present study points to a conspicuous affliction of specific precerebellar nuclei in Pick's disease. Immunoreactive punctae, probably corresponding to terminal synaptic boutons of afferent fibers, appear at sites in the inferior olive receiving intense input from the cerebral cortex. The brunt of the changes, however, are borne by the pontine gray, the arcuate nucleus, the pontobulbar body, and the paramedian reticular nucleus. Altered areas show immunoreactive punctae and an abundance of small immunoreactive nerve cells partially containing Pick bodies and Pick neurites. Again, a feature common to all the affected nuclei is that they receive major input from the cerebral cortex, while other precerebellar nuclei with preponderant input from the spinal cord and/or other noncortical sources remain unscathed or exhibit only sparse involvement. The lesional pattern which develops in specific precerebellar nuclei is interpreted to be a partial reflection of the cortical involvement of Pick's disease.

Aged↗
PubMed1998

Evolution of neuronal changes in the course of Alzheimer's disease.

Alzheimer's disease entails multiple neuronal systems and results from neuronal cytoskeletal degeneration of only a few types of nerve cells. Essential for neuropathological diagnosis is assessment of the presence of neurofibrillary tangles and neuropil threads. The destructive process begins in predisposed cortical induction sites, thereafter invading other portions of the cerebral cortex and specific sets of subcortical nuclei in a predictable sequence with little variation. The location of the tangle-bearing neurons and severity of the pathology allow the distinction of six stages in disease propagation (transentorhinal I-II: clinically silent cases; limbic III-IV: incipient Alzheimer's disease; neocortical V-VI: fully-developed Alzheimer's disease). The pattern of appearance of the neurofibrillary changes bears a striking resemblance to the inverse sequence of cortical myelination. The average myelin content is a negative image of the density of intraneuronal lipofuscin deposits. Pigment-laden neurons endowed with a long, thin, and sparsely myelinated axon are prone to develop AD-related changes. The emergence of the first neurofibrillary changes, at whatever age these occur, signals the onset of a degenerative process that persists until death. An extended period of time elapses between the beginning of histologically verifiable lesions and the appearance of initial clinical symptoms. Once initiated, however, cytoskeletal deterioration inexorably progresses, and neither remission nor recovery is observed.

Alzheimer Disease↗
PubMed1998

Evolution of Alzheimer's disease related cortical lesions.

Alzheimer's disease is an immutably progressing dementing disorder. Its major pathologic hallmark is the gradual development of neurofibrillary changes in a few susceptible nerve cell types. The cortical changes do not occur inevitably with advancing age. Once the disease has begun, spontaneous recovery or remissions are not observed. The initial changes develop in poorly myelinated areas of the temporal lobe. The destructive process then follows a predictable pattern as it extends into other cortical areas. Advanced age is not a prerequisite for the evolution of the lesions. Alzheimer's disease is thus an age-related, but not an age-dependent disease. The spread of the neurofibrillary changes resembles the process of cortical myelination, however in reverse order.

Aging↗
PubMed1998

Argyrophilic grain disease is associated with apolipoprotein E epsilon 2 allele.

Argyrophilic grain disease (AGD) is a distinct degenerative disorder of the human brain associated with the formation of abnormally phosphorylated tau protein. AGD-related cytoskeletal changes are known to affect specific subsets of nerve cells and oligodendrocytes. Here we demonstrate a remarkable association between the apolipoprotein E (ApoE) epsilon2 allele and AGD. Individuals afflicted with AGD (n = 48) reveal a significantly higher frequency of the epsilon2 allele compared with controls (n = 43) (22% versus 4%, P < 0.0002). The association between AGD and epsilon2 allele of ApoE suggests that AGD can be distinguished from other neurodegenerative disorders not only neuropathologically, but also genetically.

Aged↗
PubMed1998

Cytoskeletal alterations in the human tuberal hypothalamus related to argyrophilic grain disease.

The tuberal region of the human hypothalamus was examined for cytoskeletal changes related to argyrophilic grain disease (AGD). Hypothalamic sections of eight individuals afflicted with AGD and eight controls were cut serially in the frontal plane at 100 microm. The presence of argyrophilic AGD-related pathology was demonstrated utilizing the modified Gallyas silver iodide technique. Tau-positive cytoskeletal changes were stained by the phosphorylation-dependent antibody AT8. A characteristic pattern of tau-positive cytoskeletal alterations was revealed in the tuberal hypothalamus of AGD cases, while controls were devoid of such changes. The lateral tuberal nucleus was found to be particularly susceptible to AGD, demonstrating numerous tau-positive grains and neuronal cell bodies. Similar alterations were present to a moderate degree in the ventromedial nucleus. A previously unreported, conspicuous accumulation of tau-positive oligodendrocytes (coiled bodies) and interfascicular thread-like fibers was detected in the column of the fornix. Only sparse argyrophilic changes were noted in consecutive silver-stained sections, comprised mainly of accumulations of spindle-shaped grains within the lateral tuberal nucleus. Remarkably, a pronounced expression of AGD-related alterations was seen in the absence of hypothalamic changes related to other tau-positive cytoskeletal disorders, such as Alzheimer's disease. The present findings support the concept that AGD is a distinct neurodegenerative entity afflicting not only cortical but also subcortical predilection sites of the human brain.

Aged↗
PubMed1998

Argyrophilic grain disease: frequency of occurrence in different age categories and neuropathological diagnostic criteria.

Argyrophilic grain disease is a progressive degenerative disorder of the human brain which becomes increasingly prevalent with advancing age. The disease entails multiple neuronal systems and results from cytoskeletal degeneration in only a few neuronal types and in oligodendrocytes. Immunoreactions for abnormally phosphorylated tau protein permit identification of the changes. Only a fraction of the emerging abnormal fibrillary material shows a pronounced argyrophilia. Essential for neuropathological diagnosis is assessment of the presence of small spindle-shaped argyrophilic grains in neuronal processes. The anteromedial portion of the temporal lobe bears the brunt of the lesions. Grains generally can be found in abundance in the entorhinal region, the first Ammon's horn sector, the subcortical nuclear complex of the amygdala, and the hypothalamic lateral tuberal nucleus. Frequently, the lesions co-exist with those typically found in Alzheimer's disease or other tauopathies. Owing to the characteristic grains, the disorder easily can be differentiated from other tauopathies. 2661 non-selected brains obtained at autopsy included 125 cases of argyrophilic grain disease (5%) from individuals between 51 and 96 years of age (mean 79 years) . The fact that the same material contained 146 cases of fully developed Alzheimer's disease (6%) supports the view that argyrophilic grain disease is not a rare disorder. Its prevalence with and without concomitant neurofibrillary changes of the Alzheimer type grows with increasing age. Argyrophilic grain disease merits attention because of its frequent occurrence and its potential to cause severe brain dysfunction.

Adult↗
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

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↗