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D P Perl

Publications and source records attributed to D P Perl.

At least 91 records · Page 5Linked to original sources
PubMed1992

Aluminium and the neurofibrillary tangle: results of tissue microprobe studies.

Despite the contradictory results of studies attempting to compare the bulk brain tissue aluminium content of specimens from Alzheimer's disease patients and controls, microprobe studies from our laboratory have consistently documented evidence of selective accumulation of the element within the neurofibrillary tangle-bearing cells associated with this condition. Laser microprobe mass analysis (a highly sensitive and precise technique for trace elemental microprobe analysis) has now demonstrated that the most prominent aluminium accumulations occur within the neurofibrillary tangle itself. Similar findings have been obtained from microprobe studies of the neurofibrillary tangles which are a characteristic feature of amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam. Although the intraneuronal localization of aluminium in the Guam-derived specimens is similar to that of Alzheimer's disease, the concentration of aluminium is considerably higher than is encountered in Alzheimer's disease specimens. We conclude that aluminium is an integral component of the neurofibrillary tangle and raise the possibility that the cross-linking properties of this highly reactive metal may stabilize the constituent cytoskeletal proteins which make up this pathological structure.

Aluminum↗
PubMed1992

Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer's disease: a laser microprobe (LAMMA) study.

We report the results of an examination of the elemental content of neurofibrillary tangle-bearing and neurofibrillary tangle-free neurons identified within the hippocampus of 10 subjects with Alzheimer's disease and 4 neuropathologically intact age-matched control subjects. The study employed laser microprobe mass analysis (LAMMA), a technique that provides extremely sensitive multielement detection in plastic-embedded, semithin-sectioned tissues. Evidence for the selective accumulation of aluminum within the neurofibrillary tangle-bearing neurons was obtained in all 10 subjects with Alzheimer's disease. The site of aluminum deposition within these cells was the neurofibrillary tangle itself, and not the "nuclear region," as we previously reported. Iron accumulation was also detected within neurofibrillary tangles. Evaluation for the accumulation of other elements within the tangle-bearing neurons failed to reveal any other metallic element as being consistently present. In addition, probe sites directed to neurons identified in snap-frozen cryostat sections from 2 subjects with Alzheimer's disease revealed similar spectra with prominent aluminum-related peaks, confirming that our findings are not related to exogenous contamination through fixation, embedding, or other procedures prior to analysis. This study further confirms the association of aluminum and neurofibrillary tangle formation in Alzheimer's disease.

Aluminum↗
PubMed1992

Comparative techniques for determining cellular iron distribution in brain tissues.

Iron is essential for a number of normal brain functions and accumulates in high concentrations in specific regions of the brain. In pathological states, it may further accumulate in these and other areas that are typically low in iron content. The contribution of excess iron to potential central nervous system damage through its ability to donate an electron and to promote oxygen free radical formation has made the nature, location, extent, and process of iron deposition in the brain important areas of investigation. Nevertheless, there is relatively little information currently available on the cellular and subcellular distribution of iron in the central nervous system in either normal or diseased states. We describe and compare a number of the currently available techniques by which iron can be detected within the cellular components of the brain. Histochemical approaches, primarily in the form of the Perls' stain, yields information only on iron in its ferric state and is a relatively insensitive technique. Electron microscopy with x-ray spectrometry can provide positive identification of iron but has limitations regarding morphological verification of the specific cells being probed and also has a relatively high lowest detection limit. Secondary ion mass spectrometry and proton-induced x-ray spectrometry are both expensive, highly complex techniques with greater detection sensitivity, but they have problems identifying the cellular components being analyzed. Finally, laser microprobe mass analysis combines histological localization and identification of probe sites in plastic-embedded histological sections with detection limits in the single part per million range.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Differential distribution of neurofibrillary tangles in the cerebral cortex of dementia pugilistica and Alzheimer's disease cases.

Head trauma has been associated with the occurrence of Alzheimer's disease and plays a clear role in the etiopathogenesis of the boxers encephalopathy referred to as dementia pugilistica. Neurofibrillary tangles (NFT), one of the pathological hallmarks of Alzheimer's disease are observed in very high densities in the brains of former professional boxers suffering from dementia pugilistica. In Alzheimer's disease, NFT display striking regional and laminar distribution patterns that have been correlated with the localization of neurons forming specific corticocortical connections. In dementia pugilistica cases, NFT were concentrated in the superficial layers in the neocortex, whereas in Alzheimer's disease they predominated in the deep layers. Thus, the association cortex of brains from dementia pugilistica patients demonstrated an inverse NFT distribution as compared to Alzheimer's disease. This finding suggests that a more circumscribed population of cortical pyramidal neurons might be affected in dementia pugilistica than in Alzheimer's disease.

Aged↗
PubMed1991

Neurofibrillary tangle distribution in the cerebral cortex of parkinsonism-dementia cases from Guam: differences with Alzheimer's disease.

Parkinsonism-dementia together with amyotrophic lateral sclerosis is a highly prevalent disorder among the native Chamorro population of Guam and is accompanied by severe widespread neurofibrillary tangle formation. In the present study we compared the regional and laminar distribution of neurofibrillary tangles in the cerebral cortex of 5 Guamanian parkinsonism-dementia cases to 9 Caucasian Alzheimer's disease cases. Although in both diseases the superior frontal and inferior temporal cortex were affected to a comparable degree, there was a striking difference in the laminar distribution of neurofibrillary tangles. Neurofibrillary tangles in Alzheimer's disease are known to be more numerous in layers V-VI than in layers II-III of frontal and temporal cortex, however in the Guam cases, the opposite distribution was observed with most of the tangles located within layer II and the superior part of layer III and relatively low tangle density in layers V-VI. Interestingly, in both conditions, the hippocampal pyramidal layer showed a comparable degree of degeneration. Moreover no amyloid deposits and neuritic plaques were observed in the Guam brains, whereas they were frequent in the Alzheimer's disease cases. Previous studies have suggested that the clinical symptomatology observed in patients suffering from Alzheimer's disease is related to the dramatic loss of specific corticocortically projecting neurons in the neocortex. The present data on Guam parkinsonism-dementia further support this hypothesis, although the set of corticocortical connections affected in Guam cases might differ from that observed in Alzheimer's disease, which may contribute to some extent to the different clinical symptoms of the dementia observed in Guamanian patients.

Aged↗
PubMed1991

Aluminum, Alzheimer's disease, and the olfactory system.

In Alzheimer's disease, it has been recognized that there is a dramatic tendency for the development of neurofibrillary tangles among neurons of cortical regions associated with the olfactory system. We have demonstrated that neurofibrillary tangle-bearing neurons contain dramatically elevated levels of aluminum. The olfactory system, the only portion of the central nervous system with exposure to the external environment, is uniquely capable of uptake and transneuronal spread of exogenous substances. We argue that inasmuch as aluminum is not employed in any physiologic process, these deposits must arise from exogenous sources. Using parkinsonism-dementia complex of Guam as a model, we present data which suggest that the olfactory system is particularly vulnerable to damage and is affected very early in the disease. This supports the concept that etiologic agents of importance to this epidemic may be airborne in nature and may enter the central nervous system via the olfactory pathways.

Aluminum↗
PubMed1991

Odor identification deficit of the parkinsonism-dementia complex of Guam: equivalence to that of Alzheimer's and idiopathic Parkinson's disease.

Olfactory dysfunction is among the first signs of Alzheimer's disease (AD), idiopathic Parkinson's disease (PD), and the parkinsonism-dementia complex (PDC) of Guam. We have recently demonstrated that the odor identification and detection deficits of patients with PD are equivalent to those of patients with mild AD when subtle differences in cognitive function are statistically controlled for by analysis of covariance. In contrast, patients with progressive supranuclear palsy (PSP) and patients with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism evidence olfactory function much more similar to that of normal controls. In the present study, we administered the University of Pennsylvania Smell Identification Test and the Picture Identification Test to 24 patients with early signs of the PDC of Guam and statistically compared their test scores to those of 24 early-stage AD and 24 early-stage PD patients of similar age and gender from the United States mainland. Although the PDC group evidenced slightly more difficulty in identifying pictures than did the other 2 groups, the odor identification deficit associated with this disorder was of the same magnitude as that observed in AD and PD, suggesting that olfactory testing cannot be used to distinguish among these 3 diseases and that the olfactory dysfunction of these disorders may reflect a common neurologic substrate.

Adult↗
PubMed1991

Olfactory dysfunction in three neurodegenerative diseases.

Olfactory dysfunction is among the first signs of Alzheimer's disease (AD), idiopathic Parkinson's disease (PD), and the parkinsonism-dementia complex (PDC) of Guam. We have recently demonstrated that the odor identification and detection deficits of patients with PD are equivalent to those of patients with mild AD when subtle differences in cognitive function are statistically controlled for by analysis of covariance. In contrast, patients with progressive supranuclear palsy (PSP) and patients with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism evidence olfactory function much more similar to that of normal controls. In the present study, we administered the University of Pennsylvania Smell Identification Test and the Picture Identification Test to 24 patients with early signs of the PDC of Guam and statistically compared their test scores to those of 24 early-stage AD and 24 early-stage PD patients of similar age and gender from the United States mainland. Although the PDC group evidenced slightly more difficulty in identifying pictures than did the other 2 groups, the odor identification deficit associated with this disorder was of the same magnitude as that observed in AD and PD, suggesting that olfactory testing cannot be used to distinguish among these 3 diseases and that the olfactory dysfunction of these disorders may reflect a common neurologic substrate.

Adult↗
PubMed1990

Two decades of increasing mortality from Parkinson's disease among the US elderly.

To examine the possible role of environmental factors in the cause of Parkinson's disease (PD), we reviewed mortality trends for PD in the United States from 1962 through 1984. We found that age-specific mortality for PD in all demographic groups had changed notably during this 23-year interval. Among whites of both sexes, substantial declines were observed among the middle-aged, while notable increases were seen in the geriatric age groups. Similar changes were found in nonwhites; among nonwhites in the geriatric age range, increases of 22% to 553% were observed among women. Men generally had a 100% higher risk of death due to PD than did women. Whites were at three times the risk of nonwhites. The observed temporal changes appear to reflect improved treatment, better case ascertainment, and a true rise in the incidence of PD, particularly among the elderly. This rise may be due to preventable environmental causes and will require further investigation.

Aged↗
PubMed1990

Parkinsonism death rates by race, sex and geography: a 1980s update.

To evaluate temporal changes in the geographic distribution of Parkinson's disease (PD) mortality in the United States, we reviewed death rates for PD in the nine regions of the United States for 1980-1984. Age-adjusted mortality for all ages and for the elderly (65 years of age and older) was analyzed. Variation in PD mortality was observed among the regions for all demographic groups. The patterns were different from those reported during 1959-1961. Changing geographic patterns in mortality provide evidence for an environmental etiology for PD.

Cause of Death↗
PubMed1989

Rising mortality from motoneuron disease in the USA, 1962-84.

From 1962 to 1984, age-specific mortality for motoneuron disease (MND) in the United States rose in all demographic groups over the age of 40. The increase was seen in both men and women, and both whites and non-whites, and was most pronounced in the elderly (eg, 378% in white women aged 80-84 years). Men were at 50% higher risk than women, and whites had twice the risk of non-whites. These increases may reflect an improvement in case ascertainment, but they also seem to show a true rise in the incidence of MND, particularly among the elderly. Such an increase suggests an environmental aetiology.

Adult↗
PubMed1989

Aluminum-induced neurofibrillary degeneration affects a subset of neurons in rabbit cerebral cortex, basal forebrain and upper brainstem.

Neurofibrillary tangles in Alzheimer's disease show a predilection for cortical pyramidal and subcortical projection neurons. The antigenic composition, neuronal specificity and distribution of aluminum-induced neurofibrillary degeneration were examined in regions of rabbit brain analogous to those that develop neurofibrillary tangles in Alzheimer's disease. Neurofibrillary degeneration was induced by intraventricular instillation of aluminum chloride. In aluminum-treated rabbits, intensely immunoreactive filamentous aggregates were seen in affected neuronal perikarya after staining with an antiphosphorylated neurofilament antibody (SMI 31), while in controls immunoreactivity was confined to axon-like elements. Monoclonal antibodies against Microtubule-associated protein 2 and tau, which stain human neurofibrillary tangles, did not stain aluminum-induced neurofibrillary degeneration. Pyramidal neurons exhibiting neurofibrillary degeneration formed a discrete linear pattern in layers III and V of cortex. Cortical somatostatin and nicotinamide adenine dinucleotide phosphate diaphorase-reactive neurons identified in double-stained sections were unaffected. Large perikarya in the vicinity of the globus pallidus, some of which contained acetylcholinesterase, were frequently SMI 31-immunoreactive. Among the cell groups affected in the upper brainstem were the nucleus raphe dorsalis and locus coeruleus. These findings show that aluminum-induced neurofibrillary degeneration differs antigenically from neurofibrillary tangles in Alzheimer's disease. Nevertheless, many neuronal subsets that are particularly susceptible to Alzheimer's disease, including cortical pyramidal neurons, basal forebrain cholinergic neurons and upper brainstem catecholaminergic neurons, are also affected by aluminum-induced neurofibrillary degeneration.

Aluminum↗
PubMed1989

Multiple microabscesses in the central nervous system: a clinicopathologic study.

We reviewed 2,107 consecutive autopsies with neuropathologic examination at the Medical Center Hospital of Vermont, and identified 92 cases with significant pathologic evidence for infection involving the central nervous system (CNS). Of these, 35 took the form of multiple microabscesses. There were 19 men and 16 women, mean age 56. All patients were chronically ill, usually with an associated impaired immunity. The lung was the most frequent site of primary infection, and sepsis was often present. The most commonly identified causative organisms were Staphylococcus aureus and Candida albicans. Patients with CNS microabscesses developed a progressive encephalopathy associated with waxing and waning signs and symptoms. Laboratory and neuroradiologic studies were not helpful in elucidating the problem. We conclude that multiple microabscesses are a frequent, usually unrecognized, manifestation of CNS infection, and should be considered in the differential diagnosis of encephalopathy in hospitalized patients with chronic disease, immunosuppression and sepsis.

Adult↗
PubMed1988

Aluminum-induced neurofibrillary degeneration disrupts acquisition of the rabbit's classically conditioned nictitating membrane response.

Rabbits received intraventricular injections of aluminum chloride, hydrochloric acid, or served as unoperated controls. On the 6th day postsurgery, they underwent 4 days (100 trials per day) of classical conditioning of the nictitating membrane response (NMR) to a tone conditioned stimulus and an air-puff unconditioned stimulus. Unoperated and hydrochloric acid control animals readily acquired the conditioned response. Aluminum intoxicated rabbits, in contrast, did not acquire the conditioned response over the 4 days of testing. This disruption of conditioning in aluminum-treated rabbits could not be attributed to deficits in sensory or motor processes or to illness. Neuropathological analysis revealed widespread neurofibrillary tangle formation in aluminum-treated animals. Furthermore, the degree of neurofibrillary degeneration was significantly negatively correlated with the degree of conditioning. The results are considered in the context of using the rabbit NMR preparation as a model system for studying age-related conditioning disorders.

Aluminum↗
PubMed1988

Accumulation of phosphorylated neurofilaments in anterior horn motoneurons of amyotrophic lateral sclerosis patients.

Perikaryal collections of intermediate filaments have been described in the anterior horn motoneurons of patients with amyotrophic lateral sclerosis (ALS), but these inclusions have generally been considered rare and mainly associated with the familial form of ALS. Using the monoclonal antibody NF2F11, which recognizes phosphorylated neurofilament epitopes, we showed that focal collections of neurofilaments in anterior horn motoneurons were a characteristic finding in sporadic as well as in familial ALS; they were present in seven of nine ALS patients, but in none of nine control spinal cords. These neurofilamentous collections are not cross-reactive with antibodies directed against paired helical filaments and the microtubule associated protein tau. In addition, diffuse staining for phosphorylated neurofilament epitopes in chromatolytic anterior horn perikarya was significantly more frequent in ALS patients than in controls.

Adult↗
PubMed1988

Disrupted retention of the classically conditioned nictitating membrane response in rabbits with aluminum-induced neurofibrillary degeneration.

Rabbits underwent classical conditioning of the nictitating membrane response (NMR) to a tone conditioned stimulus and an air puff unconditioned stimulus until they emitted 90 percent or greater conditioned responses (CRs) for two consecutive days. They then received intraventricular injection of aluminum chloride, hydrochloric acid or saline. Ten days post injection they were tested for retention of the conditioned response. Animals injected with saline or hydrochloric acid emitted an average of greater than 90 percent CRs. Aluminum injected rabbits, in contrast, emitted an average of only about 40 percent CRs. This disruption of retention of conditioning in aluminum treated rabbits could not be attributed to deficits in sensory or motor processes or to illness. Neuropathological analysis revealed widespread neurofibrillary tangle formation in the aluminum treated animals. Furthermore, the degree of neurofibrillary degeneration was significantly negatively correlated with retention of the CR. The results are considered in the context of using the rabbit NMR preparation as a model system for studying age-related conditioning disorders.

Aluminum↗