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R D Terry

Publications and source records attributed to R D Terry.

At least 37 records · Page 2Linked to original sources
PubMed1993

Re-evaluation of the structural organization of neuritic plaques in Alzheimer's disease.

We re-examined the relationship among synaptic pathology, subcellular abnormalities within neurites in the plaques and beta-amyloid deposits of Alzheimer's disease (AD) using laser confocal imaging and computer-aided serial section reconstruction techniques. Analysis of serial optical sections of neuritic plaques double-immunolabeled for anti-beta-amyloid/anti-tau-2 revealed that 35% of this type of plaque contained a dense amyloid core with clusters of peripheral abnormal neurites. The other 65% were without a dense core and were mainly composed of abundant abnormal neuritic clusters with bundles of amyloid distributed throughout the neuritic plaque. While two-dimensional (2-D) analysis of the plaques has suggested that neurites are distributed in the plaque periphery with beta-amyloid localized in its center, serial section analysis showed the opposite arrangement can also be true. Three-dimensional (3-D) reconstructions of serial optical sections showed that the tau-positive tortuous axons clustered in the neuritic plaques were often continuous with synaptophysin-positive distended terminals. Analysis of electron micrographs from serial sections showed continuity among the different segments of the neurites. Further analysis of the computer generated 3-D reconstructed neuritic plaques (both from serial electron micrographs and serial optical sections), viewed as continuous rotating loops, confirmed that a great majority of the plaque volume was occupied by the clustered and continuous abnormal neurites, while the amyloid fibrils were compressed and displaced to the periphery of the plaque. The 3-D imaging of the neuritic plaques in AD suggests a more widespread and active neuritic damage than that predicted from 2-D observations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Plaque-only Alzheimer disease is usually the lewy body variant, and vice versa.

A minority of neuropathologically confirmed Alzheimer disease (AD) brains lack neocortical neurofibrillary tangles or have very few, constituting a form of "plaque-only AD." A significant percentage of clinically diagnosed AD patients are found at autopsy to have both AD and brainstem and neocortical Lewy bodies. Many of these Lewy body variants of AD (LBV) have numerous senile plaques but no neocortical neurofibrillary tangles, and so resemble plaque-only AD. In this study, we sought to determine if plaque-only AD was usually LBV, and, conversely, if LBV was usually plaque-only AD. We analyzed 147 consecutively accessioned cases of neuropathologically confirmed AD, diagnosed according to criteria from the National Institute on Aging and the Consortium to Establish a Registry for Alzheimer's Disease. Twenty-five percent of all AD cases in this series were plaque-only AD, and 75% were plaque and tangle AD. Twenty-eight percent of AD cases in this series were LBV, and 72% were pure AD. Of the plaque-only AD cases, 75% were LBV and only 25% were pure AD. Of the LBV, 66% were plaque-only AD and only 33% were plaque and tangle AD. These results indicate that most plaque-only AD is LBV, and, conversely, that most LBV is plaque-only AD.

Aged↗
PubMed1993

Quantitative synaptic alterations in the human neocortex during normal aging.

We quantified the synaptic population density in the frontal cortex of 25 individuals without dementia 16 to 98 years old, using sections double-immunolabeled for beta/A4 amyloid and for synaptophysin, and found a significant inverse correlation between the presynaptic terminal (PT) counts and age (r = -0.7, p < 0.001). Individuals older than 60 years had an average 20% decrease in PT density compared with individuals younger than 60 years. There were no significant correlations between the age and the number of beta/A4 amyloid-positive plaques or between synaptic density and the number of amyloid plaques. Further analysis of the digitized serial optical images showed focal areas of synapse loss and distended synaptophysin-containing boutons in the mature plaques of the normal aged cases. However, we found no microscopic changes in the synaptic content inside and outside the diffuse plaques. We suggest that a loss of synaptic input in the neocortex is an age-dependent factor that contributes to the overall synaptic loss in Alzheimer's disease, but that this might be largely independent of the beta/A4-amyloid deposition.

Adolescent↗
PubMed1993

Making the diagnosis of Alzheimer's disease. A primer for practicing pathologists.

There is demand on community pathologists to perform autopsies to confirm the clinical diagnosis of Alzheimer's disease, the most common cause of dementia in our increasingly aging society. Yet many pathologists are reluctant to examine autopsy brains because they have little experience with neuropathology and with the common histopathologic staining methods needed to evaluate dementia cases. This article provides interested pathologists with a simple, practical protocol to use in meeting this demand. While there is no absolute diagnostic gold standard for Alzheimer's disease and the histopathologic diagnosis remains imperfect, the guidelines presented are adapted from those used by many neuropathologists at Alzheimer's disease research centers participating in CERAD, the Consortium to Establish a Registry for Alzheimer's Disease. Recipes for appropriate stains and specific case examples are provided for convenience.

Age Factors↗
PubMed1992

Spectrum of human immunodeficiency virus-associated neocortical damage.

A spectrum of neurocognitive defects, termed human immunodeficiency virus type 1 (HIV-1)-associated cognitive/motor complex, has been described in patients with acquired immunodeficiency syndrome (AIDS). AIDS dementia complex (ADC) is a severe form of this disease seen in 20 to 30% of terminally ill patients. The etiology of this complex is distinct from commonly observed opportunistic infections seen in brains of patients with AIDS and has been attributed to HIV infection within the brain. At autopsy, the brains of patients with ADC contain numerous HIV-infected macrophages/microglia with prominent subcortical damage, together termed HIV encephalitis. We retrospectively analyzed all 107 brains from a three-year period (1988-1990) of AIDS autopsies using immunocytochemistry to detect HIV. Rather than breaking into distinct groups of HIV encephalitis versus non-HIV encephalitis, the specimens revealed a spectrum of severity of HIV infection. Although only 16% of the brains showed the histological hallmarks of HIV encephalitis, more than 50% of the autopsies showed moderate to severe HIV infection. In a subset of 23 AIDS autopsies during which short postmortem times and absence of significant opportunistic infection permitted quantitative analysis of dendritic and synaptic complexities, we identified a strong correlation between neocortical dendritic and presynaptic damage and abundance of HIV envelope protein in the neocortical gray and deep white matter. This correlation suggests that the presence of HIV-1 in the neocortex may be responsible by direct or indirect mechanisms for dendritic and synaptic damage.

AIDS Dementia Complex↗
PubMed1992

Prevention of tilorone developmental toxicity with progesterone.

The immunomodulator tilorone hydrochloride was administered (gastric intubation) once to time-pregnant Upj:TUC(SD)spf (Sprague-Dawley) rats in four experiments. In experiment 1, tilorone (250 or 500 mg/kg) was administered on day 10 of gestation. The dams were killed 4 or 72 hr after dosing. Interferon-like activity and drug levels were determined in maternal blood, spleen, and thymus, as well as in the embryos. In experiment 2, the test groups received progesterone (2 mg/kg), or tilorone (200 or 400 mg/kg), or progesterone and tilorone. The dams from each group were killed 24 or 48 hr after receiving tilorone. Experiment 3 was similar to experiment 2, except that the dams were killed on gestation day 20. In experiment 4, tilorone (400 mg/kg) was administered on gestation day 17, 18, or 19, and the dams were killed 24 hr after dosing or on gestation day 20. In all four experiments, tilorone-related maternal toxicity (regardless of whether progesterone also was administered) was observed, as characterized by marked decreases in weight gain, the occurrence of clinical signs, and in experiment 1 by decreased thymus weights, 72 hr post-dosing. Dose-related increases in the mean number of dead embryos and in serum interferon titers occurred 72 hr postdosing. In experiment 2, there was an increase in the number of dams in the 400-mg/kg (tilorone only) group with dead embryos only, 24 hr postdosing; similar results occurred in both the 200- and 400-mg/kg groups, 48 hr postdosing. However, in the groups that also received progesterone, a partial prevention of such embryolethality was evident. In experiment 3, embryotoxicity again was observed in both tilorone-treated groups, whereas several of the dams that were also given progesterone through day 19 of gestation experienced at least a partial prevention of the embryolethal effects of tilorone. In experiment 4, no fetotoxicity was observed despite the severe maternal toxicity evident.

Animals↗
PubMed1992

Three-dimensional analysis of the relationship between synaptic pathology and neuropil threads in Alzheimer disease.

Recent studies have shown that the Alzheimer disease (AD) neocortex is characterized by a loss of large neurons, the presence of dilated terminal axons, widespread loss of synapses, and a disruption of the dendritic cytoskeleton which is manifested as Tau immunoreactive threads. In the present study we have investigated the relationship between synaptic and dendritic abnormalities in the neocortex of Alzheimer patients and examined the extent to which these structural alterations correlate with the severity of cognitive impairment in AD. Quantitative neuroanatomical data were obtained from immunofluorescence-labeled specimens using a laser-scanning confocal microscope, computer-assisted image processing and serial section reconstruction techniques. We found that the AD cases showed a 34% loss in the number of presynaptic terminals per 100 square (sq) microns, many of which showed structural abnormalities. The AD neuropil had an average of 10 +/- 7 dendritic threads per 1,000 sq microns, with the average thread measuring 2 sq microns. Severe AD cases had thicker threads compared with mild to moderate AD cases. Three-dimensional analysis showed clustering of synapses around threads, as well as presynaptic boutons apposed to dendritic neuropil threads. Statistical analysis showed that the strongest correlation was between synapse density and Blessed score of cognitive impairment. Thread counts did not correlate with either but were correlated with tangle counts. Stepwise multiple regression analysis showed that tangle counts, but not threads, strengthened the correlation between Blessed score and synapses. We conclude that synaptic damage may precede dendritic thread and tangle formation, and that threads do not necessarily induce synaptic pathology. Instead, dendrite sprouting in the denervated regions could be associated with increased accumulation of cytoskeletal proteins observed in the dendritic threads.

Aged↗
PubMed1992

Cortical dendritic pathology in human immunodeficiency virus encephalitis.

Previous neuropathological and morphometric studies of the cerebral cortex of patients with human immunodeficiency virus encephalitis (HIVE) have shown a decrease in the population of large neurons, moderate loss in synaptophysin immunoreactivity, and pathological changes in dendrites. To further characterize and quantify alterations in the dendritic tree of neocortical pyramidal neurons, we performed a modified Golgi impregnation technique on Formalin fixed blocks from the frontal cortex of 5 HIVE cases, 5 human immunodeficiency virus seropositive control cases without encephalitis, and 5 human immunodeficiency virus seronegative controls. Apical dendrites of HIVE cases were dilated, vacuolated, and tortuous with decreased length and branching. Basal and oblique dendrites also showed these alterations, but to a lesser extent. Some dendrites presented lacunae and filopodia consistent with remodeling. Computer aided quantification of HIVE cases showed a 40-60% decrease in spine density throughout the entire length of dendrites. Laser confocal imaging of Golgi impregnated sections displayed aberrant spines in regions of abnormal second order dendritic branches. These observations support the role of primary dendritic damage in HIVE in contrast to other neurodegenerative disorders where the primary pathology is presynaptic.

AIDS Dementia Complex↗
PubMed1992

Weight-related behaviors and concerns of fourth-grade children.

Behaviors and concerns related to weight were measured among 457 fourth-grade children attending 10 rural schools in central Iowa. A questionnaire was used to gather data on the children's concerns about being overweight, concerns that certain types or amounts of food would contribute to their being overweight, alterations in food intake to avoid being overweight, and perceptions that peers and family members were concerned about being overweight. In addition, each child's height and weight were measured. Weight-related behaviors and concerns increased with increasing weight-for-age and body mass index (BMI) and were more prevalent among girls than boys. The frequency of drinking diet soft drinks was positively correlated with weight-for-age and BMI and tended to increase with an increase in weight-related behaviors and concerns. Girls were more likely than boys to report a desire to be thinner (60.3% vs 38.4%), whereas boys were more likely than girls to want to be taller (67.2% vs 49.1%). The desire for less body fat was significantly associated with an increase in the frequency of weight-related behaviors and concerns, the frequency of drinking diet soft drinks, weight-for-age, and BMI. These findings indicate a need for interventions that combat fear of obesity and restrictive eating among growing children.

Anthropometry↗
PubMed1991

Abnormal brain spectrin immunoreactivity in sprouting neurons in Alzheimer disease.

Brain spectrin is a major membrane skeleton protein that participates in cellular transport, cell morphogenesis, neurotransmitter release and growth cone adhesion. The present study showed that in Alzheimer disease (AD) neuropil, brain spectrin immunoreactivity is co-localized with synaptophysin in the presynaptic boutons. At the ultrastructural level, brain spectrin immunoreactivity was observed in the presynaptic terminals and in the axoplasm of some myelinated and unmyelinated fibers. In addition to this normal localization of brain spectrin in the AD brain, we also found brain spectrin immunoreactivity associated with abnormal patchy lesions in the AD neuropil. Confocal laser imaging and immunoelectron microscopy revealed that these lesions corresponded to thick cellular processes derived from neurons. The findings that these structures were anti-neurofilament positive but anti-glial fibrillary acidic protein (GFAP) and Ricinus communis agglutinin I (RCA-I) negative confirm their neuronal origin, and rule out the possibility of glial origin. These structures could represent either atypical axonal or dendritic processes derived from sprouting neurons or the accumulation of brain spectrin degradation products in degenerating neurons.

Aged↗
PubMed1991

Alcohol-induced brain changes in dogs.

We studied the neuropathologic effects of chronic alcohol ingestion on the brains of healthy, well-nourished, male mongrel dogs. Five experimental dogs were provided 36% of their calories as ethyl alcohol for 1 year. Following killing, their brains were weighed, photographed, sectioned, and processed for computerized morphometric determinations of ventricular size, cortical thickness, and neocortical neuron and glial cell populations. Compared with a similarly handled control group, the alcoholic dog brains showed lateral ventricular enlargement, cortical thinning in the temporal lobe only, and fewer glial cells in the temporal and frontal cortices. There were no statistically significant differences between the alcoholic and control groups in brain weight, frontal or parietal cortical thickness, or neocortical neuron populations. These results imply a disproportionate vulnerability of white matter to the damaging effects of alcohol with consequent lateral ventricular enlargement, and some regional variation in neocortical susceptibility to alcohol-induced cortical thinning and glial cell loss. In general, such changes are consistent with those described in neuroradiologic imaging studies of human alcoholics.

Alcoholism↗
PubMed1991

Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment.

We present here both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of 15 patients with Alzheimer's disease and 9 neuropathologically normal subjects. The statistical data show only weak correlations between psychometric indices and plaques and tangles, but the density of neocortical synapses measured by a new immunocytochemical/densitometric technique reveals very powerful correlations with all three psychological assays. Multivariate analysis by stepwise regression produced a model including midfrontal and inferior parietal synapse density, plus inferior parietal plaque counts with a correlation coefficient of 0.96 for Mattis's Dementia Rating Scale. Plaque density contributed only 26% of that strength.

Aged↗
PubMed1991

Immunoelectron microscopic study of synaptic pathology in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by an extensive loss of neurons and synapses in the neocortex which correlates strongly with psychometric tests of dementia. To characterize the ultrastructural changes in presynaptic terminals in AD, we studied biopsy material from the frontal cortex. We also examined, at the ultrastructural level, abnormal neurites scattered in the AD neuropil and in the plaque region using sections from autopsy material immunolabeled with anti-synaptophysin. We found that, regardless of amyloid deposits, some presynaptic terminals were distended and contained swollen vesicles and dense bodies. These altered synaptic organelles were similar to those found in dystrophic neurites. The latter structures displayed synaptophysin immunoreactivity, mostly localized to outer membranes of synaptic vesicles and dense bodies. The present study supports the hypothesis of progressive synaptic pathology in AD neocortex and favors the notion that the dystrophic process originates from presynaptic terminals.

Aged↗
PubMed1991

Reactive synaptogenesis assessed by synaptophysin immunoreactivity is associated with GAP-43 in the dentate gyrus of the adult rat.

Reactive synaptogenesis and terminal proliferation are known to occur in the dentate gyrus of the rat hippocampus following removal of specific afferents. In the present study we have examined the relation of synaptophysin immunoreactivity to the immunohistochemical staining pattern of GAP-43, a putative marker of neuritic growth. Within the molecular layer of the normal dentate gyrus, synaptophysin immunolabeling shows a trilaminar pattern, with the inner and outer layers having the greatest density of staining. Within the first week following denervation, there was a significant decrease in the staining density in the outer two-thirds of the molecular layer, followed by a moderate recovery at 14 days and 80% recovery by 30 days. This pattern is consistent with the time course of denervation and reinnervation in this system as determined previously by electron microscopy. By comparison, the staining pattern for GAP-43 in the intact dentate gyrus showed the middle and outer thirds of the molecular layer to be less densely stained than the inner third. Within a week following deafferentation, the outer two-thirds of the molecular layer displayed decreased levels of GAP-43 immunoreactivity, followed by recovery to normal levels by 30 days. By 84 days postlesion, patterns of both synaptophysin and GAP-43 immunostaining reflected an increased width of the inner molecular layer. Laser confocal imaging of double-immunolabeled sections at 14 days postlesion showed a 370% increase in the number of GAP-43-positive terminals in the molecular layer as compared to unoperated controls. Many of these GAP 43-positive terminals were synaptophysin negative. We conclude that GAP-43 may play a role in the synaptic remodeling that occurs in the denervated rat hippocampus and that quantitative morphometry of synaptophysin immunolabeling accurately reflects the fate of presynaptic terminals in this model of degeneration and reinnervation.

Animals↗
PubMed1991

Protein kinase C alteration is an early biochemical marker in Alzheimer's disease.

Neuritic (senile) plaques are a hallmark of the pathology found in the brain of patients afflicted with Alzheimer's disease (AD). Neuritic plaques have been considered to be composed of an amyloid core surrounded by dilated neurites, although the use of anti-beta/A4-protein antibody revealed the presence of diffuse plaques without a nuclear-like central mass or surrounding paired helical filament (PHF)-containing neuritic components. The presence of diffuse plaques without PHF-containing neuritic components strongly suggests that the formation of amyloid precedes the degeneration of neurites that surround amyloid. Diffuse plaques are thus considered to be an early marker of AD pathology. In this article, we report that diffuse plaques, possible markers of early AD pathology, are immunostained with anti-protein kinase C(beta II) [anti-PKC(beta II)] antibodies. The PKC(beta II)-immunoreacting components of the diffuse plaques extend from neurons embedded in the plaques. Immunoelectron microscopy of diffuse and mature neuritic plaques shows that PKC(beta II)-like immunoreactivity in the plaques is closely associated with membranous structures of fine neuronal processes apposed to the amyloid fibers. These fine neuronal processes are distinct from classical neurites found typically in mature neuritic plaques. Furthermore, biochemical analysis demonstrates that PKC abnormalities, but not other AD markers (ubiquitin and A68), were found in the neocortex of clinically nondemented individuals with cortical plaques. Therefore, the PKC alteration in neurons might be involved in the early pathophysiology of AD.

Alzheimer Disease↗
PubMed1991

Cortical and subcortical patterns of synaptophysinlike immunoreactivity in Alzheimer's disease.

Quantification of synaptophysinlike immunoreactivity is a valuable method for studying the presynaptic terminals in the normal and damaged nervous system. The present report shows that in the control brain, the predominant pattern of synaptic immunostaining in the neocortex was that of an evenly distributed densely granular immunolabeling of the neuropil, while in the paleocortex and in subcortical areas of the brain most of the presynaptic terminals were distributed along the dendritic arborizations or around the neuronal somata. The immunochemical and the immunohistochemical analysis of the Alzheimer's disease tissue showed that the frontal and parietal cortex presented the most severe and widespread loss, with a 45% loss in synaptophysin immunoreactivity. These areas showed an average 35% loss of large neurons. The visual cortex, hippocampus, entorhinal cortex, nucleus basalis of Meynert, and locus ceruleus displayed some degree of loss, but to a lesser extent. In addition to this loss, the basic patterns of organization of the presynaptic terminals were altered, with the presence of abundant, enlarged synaptophysin-labeled terminals. This study further supports the role of synaptic pathology in Alzheimer's disease.

Aged↗