Cytoskeletal pathology in neurodegenerative diseases.
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Alzheimer Disease↗
Biomedical subjects
D P Perl
Publications and source records attributed to D P Perl.
Adult onset Hallervorden-Spatz disease with neurofibrillary pathology. A discrete clinicopathological entity.
Three adults with progressive cognitive decline and extrapyramidal dysfunction were studied. They were all mentally retarded women without known chromosomal abnormalities, ranging in age at the time of onset from 31 to 42 yrs with an average duration of illness of 6 yrs. Neurological signs were stereotyped and consisted of a unilateral equinovarus foot posture followed by progressive dementia, rigidity and quadriparesis. Identical pathological findings were noted in all cases. There was marked deposition of iron-containing pigments in the globus pallidus and reticulate zone of the substantia nigra. Numerous axonal spheroids were noted in these areas and in the gracile and cuneate nuclei. In addition to these typical changes of Hallervorden-Spatz disease (HSD), abundant neurofibrillary tangles (NFTs) were found within the hippocampus, neocortex, nuclei of basal forebrain, subthalamic nucleus and brainstem reticular formation. Rare Hirano bodies and granulovacuolar degeneration were noted within the hippocampus; neuritic plaques and amyloid deposits were absent. Ultrastructurally the NFTs were mostly paired helical filaments (PHFs) with a diameter of 20 to 25 nm and a half-periodicity of 80 nm. Straight filaments and incompletely twisted forms were also seen. Immunocytochemistry with polyclonal antibodies to PHFs was positive in a distribution identical to that of Bodian-positive NFTs. Biochemical analysis of frozen frontal cortex from 1 case revealed a 94% depletion of the cholinergic marker enzyme choline acetyltransferase. Somatostatin-like immunoreactivity was within normal range. Study of 1 case with laser microprobe mass analysis revealed evidence of aluminium accumulation in tangle-bearing hippocampal neurons. Adjacent tangle-free neurons failed to show comparable accumulations. These findings indicate that adult onset HSD occurring in mentally retarded individuals may represent a distinct clinicopathological entity associated with neurofibrillary pathology without amyloid deposition.
Adult↗
Comparison of cytomegalovirus infection of brain and lung in a patient with subacute encephalopathy of acquired immunodeficiency syndrome.
The ultrastructure of cytomegalovirus infection of glial cells in an area of demyelination in the brain of a patient with subacute encephalopathy associated with acquired immunodeficiency syndrome is described. By comparison with the lung of the same patient, the cytomegalovirus-infected brain showed a lower density of complete virions per cell and a higher proportion of defective viral particles.
Acquired Immunodeficiency Syndrome↗
The association of aluminum Alzheimer's disease, and neurofibrillary tangles.
Alzheimer's disease is a progressive neurodegenerative disease characterized by the development of large numbers of neurofibrillary tangles in certain neuronal populations. Aluminum salts inoculated into experimental animals produce neurofilamentous lesions which are similar, but not identical, to the neurofibrillary tangle of Alzheimer's disease. Although a few reports suggest evidence of increased amounts of aluminum in the brains of Alzheimer's disease victims, such bulk analysis studies have been difficult to replicate. Using scanning electron microscopy with x-ray spectrometry, we have identified accumulations of aluminum in neurofibrillary tangle-bearing neurons of Alzheimer's disease. Similar accumulations have been identified in the neurofibrillary tangle-bearing neurons found in the brains of indigenous natives of Guam who suffer from parkinsonism with dementia and from amyotrophic lateral sclerosis. This ongoing research still cannot ascribe a causal role of aluminum in the pathogenesis of the neurofibrillary tangle; however, it does suggest that environmental factors may play an important part in the formation of this abnormality.
Aluminum↗
Familial myoclonic dementia masquerading as Creutzfeldt-Jakob disease.
We describe a kindred with 7 confirmed and 2 probable cases of subacute dementia accompanied by myoclonus. The inheritance pattern is consistent with autosomal dominance and shows anticipation. The pathological changes involve marked gliosis with neuronal loss of the dorsomedial and midline thalamic nuclei, with lesser involvement of the anterior, lateral, and posterior thalamic nuclei. Medullary olivary hypertrophy is prominent. Spongiform change is minimal or absent. Attempted disease transmission to primates from 3 affected family members has been unsuccessful; Western immunoblot tests have likewise failed to detect the presence of specifically reactive 27-30 kD Mr proteins in brain tissue from 2 of these patients. We conclude that this family has a rare inherited neurological systems degeneration with associated thalamic dementia, the clinical course of which is very similar to Creutzfeldt-Jakob disease.
Adult↗
An immunocytochemical comparison of cytoskeletal proteins in aluminum-induced and Alzheimer-type neurofibrillary tangles.
Exposure of the central nervous system (CNS) of rabbits to aluminum salts produces a progressive encephalopathy. Examination of CNS structures discloses widespread perikaryal neurofibrillary tangle (NFTs) formation. The aluminum-induced NFTs consist of collections of normal neurofilaments, and differ ultrastructurally and in their solubility characteristics from Alzheimer-type NFTs, the latter being composed of largely insoluble paired helical filaments. The present study compares NFTs found in the rabbit to those of Alzheimer's disease, using monoclonal antibodies (SMI 31, SMI 32) that recognize phosphorylated and non-phosphorylated determinants respectively in normal neurofilaments, and an antiserum raised against purified microtubules. Paraffin-embedded sections were stained by the avidin-biotin immunocytochemical method. Intense staining of aluminum-induced NFTs was found after processing with SMI 31 and SMI 32, while no staining of non-tangled perikarya of control rabbits or of Alzheimer-type NFTs was seen. Antimicrotubule anti-serum gave weak, nonfocal staining in the aluminum-treated and control rabbits, while Alzheimer-type NFTs were stained intensely. These results show that phosphorylated and non-phosphorylated neurofilaments accumulate in aluminum-induced NFTs, thus complementing the previously demonstrated specific slowing of the axonal transport of neurofilaments in aluminum intoxication. Further, they suggest that the presence of microtubular proteins may be necessary for altered neurofilaments to take on a paired helical configuration.
Aluminum↗
Aluminum neurotoxicity--potential role in the pathogenesis of neurofibrillary tangle formation.
Alzheimer's disease is a progressive neurodegenerative disease characterized neuropathologically by the development of large numbers of neurofibrillary tangles in certain neuronal populations of affected brains. This paper presents a review of the available evidence which suggests that aluminum is associated with Alzheimer's disease and specifically with the development of the neurofibrillary tangle. Aluminum salts inoculated into experimental animals produce neurofilamentous lesions which are similar, though not identical, to the neurofibrillary tangle of man. Although a few reports have suggested evidence of increased amounts of aluminum in the brains of Alzheimer's disease victims, such bulk analysis studies have been difficult to replicate. Using scanning electron microscopy with x-ray spectrometry, we have identified accumulations of aluminum in neurofibrillary tangle-bearing neurons of Alzheimer's disease. Similar accumulations have been identified in the neurofibrillary tangle-bearing neurons found in the brains of indigenous natives of Guam who suffer from parkinsonism with dementia and amyotrophic lateral sclerosis. This ongoing research still cannot ascribe a causal role of aluminum in the pathogenesis of neurofibrillary tangle formation; however, it does suggest that environmental factors may play an important part in the formation of this abnormality.
Aluminum↗
Neuropathology of dementia.
This article summarizes the neuropathologic changes seen in several of the more common disorders that lead to dementia. The most important, Alzheimer's disease, is characterized by the widespread development of neurofibrillary tangles and senile or neuritic plaques in the hippocampus and neocortex. Another important underlying cause of dementia is multiple infarction (so-called multi-infarct dementia), in the form of numerous cortical lesions, multiple basal ganglia lacunar infarcts, or multiple white matter infarctions. The pathologic changes associated with other forms of dementing illnesses are also briefly discussed.
Aged↗
Potential human health effects of acid rain: report of a workshop.
This report summarizes the potential impact of the acid precipitation phenomenon on human health. There are two major components to this phenomenon: the predepositional phase, during which there is direct human exposure to acidic substances from ambient air, and the post-depositional phase, in which the deposition of acid materials on water and soil results in the mobilization, transport, and even chemical transformation of toxic metals. Acidification increases bioconversion of mercury to methylmercury, which accumulates in fish, increasing the risk to toxicity in people who eat fish. Increase in water and soil content of lead and cadmium increases human exposure to these metals which become additive to other sources presently under regulatory control. The potential adverse health effects of increased human exposure to aluminum is not known at the present time.
Acids↗
Relationship of aluminum to Alzheimer's disease.
Alzheimer's disease is a progressive degenerative brain disease of unknown etiology, characterized by the development of large numbers of neurofibrillary tangles and senile plaques in the brain. Aluminum salts may be used experimentally to produce lesions which are similar, but not identical, to the neurofibrillary tangle. Although some studies have reported increased amounts of aluminum in the brains of Alzheimer's disease victims, these bulk analysis studies have been difficult to replicate and remain controversial. Using scanning electron microscopy with X-ray spectrometry, we have investigated this question on the cellular level. We have identified abnormal accumulations of aluminum within neurons derived from Alzheimer's disease patients containing neurofibrillary tangles. Similar accumulations have been detected in the numerous neurofibrillary tangle-bearing neurons seen in the brains of the indigenous native population of the island of Guam who suffer from amyotrophic lateral sclerosis and parkinsonism with dementia. Epidemiologic evidence strongly suggests a causal role for local environmental conditions relating to availability of aluminum, calcium, and magnesium. In view of the fact that a major consequence of acid rain is the liberation of large amounts of aluminum in bioavailable forms, concerns are raised about possible human health risks of this environmental phenomenon.
Acids↗
Neuropathologic evaluation of 40 confirmed cases of Legionella pneumonia.
Autopsy examination of the brain was performed in 40 cases of Legionella pneumonia. Thirty-nine of 40 patients had underlying chronic or acute medical problems. Sixteen patients (40%) had neurologic signs or symptoms that were not explained by preexisting disease. CSF was normal in six of seven patients examined; CSF protein content was 66 mg/100 ml in one patient. Neuropathologic examination in all 40 patients demonstrated no lesions attributable to disseminated Legionella pneumophila. Mechanisms other than direct cerebral invasion by the causative organism must be sought to explain the neurologic manifestations of Legionella pneumonia.
Adolescent↗
Continuous infusion of epidural anesthesia and posterior column deterioration.
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Anesthesia, Epidural↗
Intraneuronal aluminum accumulation in amyotrophic lateral sclerosis and Parkinsonism-dementia of Guam.
Scanning electron microscopy with energy-dispersive x-ray spectrometry was used to analyze the elemental content of neurofibrillary tangle (NFT)-bearing and NFT-free neurons within the Sommer's sector (H1 region) of the hippocampus in Guamanian Chamorros with amyotrophic lateral sclerosis and parkinsonism-dementia and in neurologically normal controls. Preliminary data indicate prominent accumulation of aluminum within the nuclear region and perikaryal cytoplasm of NFT-bearing hippocampal neurons, regardless of the underlying neurological diagnosis. These findings further extend the association between intraneuronal aluminum and NFT formation and support the hypothesis that environmental factors are related to the neurodegenerative changes seen in the Chamorro population.
Aged↗
Denervation modulated changes in mouse skeletal muscle RNA concentration.
We have examined normal and denervated mouse skeletal muscle for histological evidence of changes in RNA concentration using acridine orange/nucleic acid fluorescence. In denervated muscle, cytoplasmic RNA concentration increases dramatically. The earliest increase is in the subsarcolemmal region, 7 days after denervation. By 28 days after denervation, the increase in RNA is distributed throughout the cytoplasm of the atrophic cells, non-atrophic cells show little or no increase. Prior to the increase in cytoplasmic RNA concentration, many myocyte nuclei exhibit enlarged nucleoli, indicative of active ribosomal RNA synthesis. Such active nucleoli are present throughout the 42 day study period. We conclude that both new RNA synthesis, and preferential accumulation of cytoplasmic RNA are prominent events in denervation atrophy. There is an ordered progression from nucleolar synthesis to subsarcolemmal accumulation to diffuse accumulation in atrophying cells. These observations complement biochemical findings of others which indicate an increase in both RNA and protein synthesis after denervation.
Animals↗
Oculopharyngeal muscular dystrophy. An autopsied case from the French-Canadian kindred.
We report the complete autopsy findings of a 60-year-old, 12th generation member of the French-Canadian family originally described with oculopharyngeal muscular dystrophy. This report represents the second complete autopsy described in this disease. We show that oculopharyngeal muscular dystrophy is a systemic myopathy with a marked predeliction for extraocular and non-somatically derived muscles. In addition, we present a comprehensive literature review of the disease, including recent therapeutic manipulations to alleviate the major symptoms. Oculopharyngeal muscular dystrophy must be considered as a distinct, well-defined, autosomal dominant systemic myopathy of later life whose etiology remains obscure.
Blepharoptosis↗
Immunohistochemical demonstration of Toxoplasma gondii.
A peroxidase-antiperoxidase method that demonstrates both free and encysted toxoplasmata in routinely prepared histologic sections is described. This technic and ultrastructural study were employed to confirm the presence of Toxoplasma gondii in the infected tissues of an immunosuppressed patient who had postmortem examination. An immunohistochemical method may be an aid in the diagnosis of toxoplasmosis.
Adult↗
Alzheimer's disease: X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons.
The elemental content of neurons of the hippocampus was studied by a combination of scanning electron microscopy and x-ray spectrometry in autopsy-derived brain tissue from three cases of senile dementia (Alzheimer type) and three nondemented elderly controls. Foci of aluminum were detected within the nuclear region of a high percentage of neurons containing neurofibrillary tangles from the cases of senile dementia as well as the elderly controls. The adjacent normal-appearing neurons from both groups of patients were virtually free of detectable aluminum. These findings suggest that the association of aluminum to Alzheimer's disease extends to the neuronal level.
Aluminum↗
Acridine orange-nucleic acid fluorescence. Its use in routine diagnostic muscle biopsies.
Acridine orange-RNA fluorescence in diagnostic muscle biopsies is a sensitive, specific method to identify single fibers undergoing neurogenic atrophy. Fibers thus identified may be clearly distinguished from nonfluorescent type-specific atrophic fibers, as well as from atrophic fibers encountered in other myopathic conditions. Regenerating fibers, inflammatory cells, and mast cells stain prominently with acridine orange but area easily identified by their morphologic features. Acridine orange-RNA fluorescence is extremely useful in the evaluation of early neurogenic atrophy without fiber-type grouping and may be performed on paraffin-embedded sections, thus allowing retrospective studies. In addition, this technique may provide clues to the pathogenesis of neuromuscular disease that involves altered nucleic acid metabolism.
Acridine Orange↗