Biomedical subjects

J H Morrison

Publications and source records attributed to J H Morrison.

At least 127 records · Page 7Linked to original sources

PubMed1990

Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease: I. Superior frontal and inferior temporal cortex.

Various cytoskeletal proteins have been implicated in the cellular pathology of Alzheimer's disease. A monoclonal antibody (SMI32) that recognizes nonphosphorylated epitopes on the medium (168 kDa) and heavy (200 kDa) subunits of neurofilament proteins has been used to label and analyze a specific subpopulation of pyramidal neurons in the prefrontal and inferior temporal cortices of normal and Alzheimer's disease brains. In Alzheimer's disease, the distribution of neuropathological markers predominates in layers III and V in these association areas. In these neocortical regions, SMI32 primarily labels the perikarya and dendrites of large pyramidal neurons, predominantly located within layers III and V. In Alzheimer's disease, a dramatic loss of SMI32-immunoreactive (ir) cells was observed, affecting particularly the largest cells (i.e., cells with a cross-sectional perikaryal area larger than 350 microns 2). The staining intensity of the largest SMI32-ir neurons was significantly reduced in Alzheimer's disease cases, suggesting that an inappropriate phosphorylation of these cytoskeletal proteins may take place in the course of the pathological process. In addition, the SMI32-ir neuron loss and total neuron loss were highly correlated with neurofibrillary tangle counts, whereas such a correlation was not observed with neuritic plaque counts. These quantitative data suggest that SMI32-ir neurons represent a small subset of pyramidal cells that share certain anatomical and molecular characteristics and are highly vulnerable in Alzheimer's disease. Other studies have suggested that SMI32-ir neurons are likely to furnish long corticocortical projections. Thus, their loss would substantially diminish the effectiveness of the distributed processing capacity of the neocortex, resulting in a neocortical isolation syndrome as reflected by the clinical symptomatology observed in these patients. Such correlations between the expression of a selective cellular pathology and specific elements of cortical circuitry will increase our understanding of the molecular and cellular characteristics underlying a given neuronal subclass vulnerability in Alzheimer's disease or other neurodegenerative disorders.

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PubMed1990

Quantitative analysis of a vulnerable subset of pyramidal neurons in Alzheimer's disease: II. Primary and secondary visual cortex.

In this study we investigated the primary and secondary visual areas of normal and Alzheimer's disease brains by using the SMI32 antibody. It is known that in Alzheimer's disease primary sensory areas are usually less devastated than association cortices, although visual symptomatology has been documented early in the course of the disease. In area 17, the SMI32 antibody primarily labeled the perikarya and dentritic tree of the large Meynert cells and cells in layer IVB. Smaller neurons in layers III, V, and VI were also immunoreactive (ir). In area 18, very large SMI32-ir pyramidal neurons in layers III and V were observed. In both areas, staining intensity was correlated with cell size, the largest neurons being the most intensely stained. Only a few changes were observed in the Alzheimer's disease cases. The only statistically significant differences in SMI32-ir neuron counts between control and Alzheimer's disease brains occurred in layer IVB cells and Meynert cells in area 17, and in layer III cells in area 18. In contrast with association cortices, there were no changes in staining intensity in the visual areas. There were fewer neurofibrillary tangles and neuritic plaques in these areas than in prefrontal and inferior temporal cortex, and a correlation between neurofibrillary tangle counts and SMI32-ir neuron loss was only observed in layer III of area 18. These observations show that in the primary and secondary visual cortex, SMI32 also labeled a distinct subset of pyramidal cells that are known from data obtained in the monkey brain to furnish long corticocortical as well as subcortical projections. Interestingly, although there is much less cell and/or neurofibrillary tangle formation in these occipital regions than in prefrontal and temporal association areas, there is significant loss within key subsets of pyramidal cells. The selective loss of this particular subpopulation of pyramidal neurons will disrupt association pathways linking primary visual cortex with areas involved in higher level visual processing. The partial disconnection of such pathways may be relevant to the visual symptomatology frequently observed in Alzheimer's disease patients. These data further support the hypothesis that subtypes of pyramidal neurons with specific anatomical and molecular profiles may display a differential vulnerability in Alzheimer's disease.

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PubMed1990

Morphology of the cells within the inferior temporal gyrus that project to the prefrontal cortex in the macaque monkey.

The primate neocortex possesses an extraordinary degree of regional specialization. Virtually all cortical functions are dependent upon a complex system of reciprocal connections between related cortical regions that allow for distributed information processing. Although some aspects of the organization of these corticocortical projections are understood, little is known about the morphology and afferents to the cells of origin of long corticocortical projections in primates. We combined intracellular injection of Lucifer Yellow (LY) in fixed tissue with in vivo retrograde transport of fast blue to study the dendritic morphology of neurons within the inferior temporal gyrus (ITG) and the superior temporal sulcus (STS) that furnish corticocortical projections to the prefrontal cortex. The fast blue retrogradely labeled cells formed two clearly defined bands within the inferior temporal cortex: a supragranular band that corresponded to layer III, and an infragranular band that corresponded to layers V and VI. After Lucifer Yellow intracellular filling, these retrogradely labeled cells projecting to the prefrontal cortex were found to be morphologically very heterogeneous. Although all filled cells had spiny dendrites, they presented a wide range of cell body sizes and dendritic tree morphologies. In layer III, the majority of cells were typical pyramids of various sizes. In layers V-VI, numerous typical pyramidal cells were present. In addition, significant numbers of modified pyramidal forms were found, including vertical and horizontal fusiform cells, asymmetrical pyramids and multipolar cells. The entire dendritic arbor of individual subtypes in layers III, V, and VI was restricted to a few cortical layers, but as a group these cells had dendrites spanning the whole cortical depth. We suggest that corticocortically projecting cells are distinct from subcortically projecting cells and consist of a defined set of morphological and functional subgroups, each of which is driven by a distinct set of afferents and likely possesses different response properties.

Animals↗

PubMed1990

Somatostatin immunohistochemistry of hippocampal slices with lucifer yellow-stained pyramidal neurons responding to somatostatin.

We have combined electrophysiology and immunohistochemistry to study the somatostatin (SS) innervation of neurons in the rat hippocampal slice. After recording the intracellular response of a pyramidal CA1 neuron in vitro to SS, Lucifer Yellow was injected into the cell and the slice fixed and processed for immunohistochemical localization of SS in the vicinity of the recorded neuron. Most pyramidal neurons (70%) responded to SS with a hyperpolarization associated with marked slowing of spontaneous discharge and reduced input resistance. SS-containing elements either crossed, ran parallel or seemingly terminated on the Lucifer Yellow-filled SS-responsive cell. These occurrences of close proximity of apparent pre- and postsynaptic elements were observed in all layers of the CA1 region and may represent synaptic terminations of SS elements on a pyramidal neuron that are likely to elicit membrane hyperpolarizations.

Animals↗

PubMed1990

Selective disconnection of specific visual association pathways in cases of Alzheimer's disease presenting with Balint's syndrome.

During a recent clinical and neuropathological evaluation of a large autopsy population of brains our attention was drawn to a subset of patients with Alzheimer's disease (AD) presenting with a major impairment of visuospatial skills referred to as Balint's syndrome. In this subset a shift in the distribution of certain pathological profiles had occurred in that the visual areas of the occipital and posterior parietal regions had an increased number of lesions, whereas the prefrontal cortex had fewer lesions than usually observed in AD. Previous quantitative analyses have shown that generally in AD, primary sensory cortical areas are less damaged than association areas of the frontal and temporal lobes, as demonstrated by the laminar and regional distribution of two neuropathological features of the disease, neurofibrillary tangles and neuritic (senile) plaques. The distribution of pathological lesions in the AD cases with Balint's syndrome revealed that specific visual association pathways were disrupted, which are normally spared in AD. These data suggest that in some cases of AD, the particular psychological and neurological symptomatology may be caused by the selective loss of specific corticocortical systems, as reflected in the differential distribution of the neuropathological markers of the disease.

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PubMed1989

Balint's syndrome in Alzheimer's disease: specific disruption of the occipito-parietal visual pathway.

Previous quantitative neuropathologic analyses have shown that the association cortices of the temporal and frontal lobes are more damaged than the visual regions of the occipital lobe in Alzheimer's disease. In the present paper, we report on a subpopulation of Alzheimer's disease patients presenting a visual defect referred to as Balint's syndrome, and displaying a global caudal shift in pathology. Balint's syndrome is a defect in visuospatial skills, and the distribution of pathology suggests that the connections underlying this functional component of the visual system are devastated, whereas they are normally spared in Alzheimer's disease. These results suggest that multiple subtypes of Alzheimer's disease exist with differential distribution of pathology and corresponding neurologic symptomatology, and that neuritic plaque and neurofibrillary tangle formation involve the loss of specific corticocortical projections associated with specific functional deficits and identifiable neurologic syndromes.

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PubMed1989

Ultrastructural analysis of somatostatin-immunoreactive neurons and synapses in the temporal and occipital cortex of the macaque monkey.

Somatostatin-containing neurons and terminals have been analyzed in monkey temporal and occipital cortex by using light and electron microscopic immunohistochemistry. An antibody against Somatostatin-28, that was shown previously preferentially to label fibers (Morrison et al.: Brain Research 262:344-351, 1983), was utilized. As expected, few cell bodies were labeled. At the electron microscopic level, labeled cells presented a characteristic asymmetric position of the nucleus and very few symmetric or asymmetric synapses on the somatic surface. In all areas examined, somatostatin fibers formed a dense plexus in the most superficial layers (I-upper III). The density of labeled fibers in intermediate (deep III-IV) and deep layers (V-VI) varied considerably among areas. The synaptic relationships of the immunoreactive fibers were analyzed and postsynaptic targets quantified in V1, V2, and the superior and inferior temporal gyrus (STG and ITG, respectively). The synapses formed by somatostatin-labeled boutons were of the symmetric type (type II) and the primary postsynaptic targets were dendritic shafts. No regional differences were found in the distribution of the postsynaptic targets in layers I-upper III. The pattern of synapses in the deep layers was examined in STG. The frequency and distribution of postsynaptic targets was similar to the superficial layers of STG and the other temporal and occipital regions. In intermediate layers of the temporal cortex areas there was an increase in the proportion of synapses on dendritic spines. In a correlated light and electron microscopic analysis we examined synapses made by radial fibers in these regions and found that although the main targets are distal dendritic shafts, almost 40% of synapses were on dendritic spines. We suggest that the radial fibers may originate from a specialized interneuron, previously described as the double bouquet cell, and that this particular subset of somatostatin-containing double bouquet cells is likely to exhibit a very high degree of regional heterogeneity with a preference for association cortices with extensive corticocortical convergence.

Animals↗

PubMed1989

Noradrenergic innervation of monkey prefrontal cortex: a dopamine-beta-hydroxylase immunohistochemical study.

Norepinephrine has been implicated in the regulation of a number of cortical functions, yet relatively little is known about the anatomical organization of noradrenergic axons in the expanded and highly differentiated prefrontal cortex of primates. In this study, the distribution of fibers containing dopamine-beta-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine, was characterized immunohistochemically in the prefrontal cortical regions of Old World cynomolgus monkeys (Macaca fascicularis) and New World squirrel monkeys (Saimiri sciureus). In both species, differences in the density of DBH-labeled fibers were detected both across and within many prefrontal cytoarchitectonic regions. In cynomolgus monkeys, area 8B had the greatest density of DBH-immunoreactive fibers; within this region, the medial surface had a greater density of labeled processes than the dorsal surface. Areas 9 and 24 also had a high density of DBH-labeled fibers, areas 11, 12, 13 and 25 were of intermediate density, and portions of areas 10 and 46 had the lowest density of immunoreactive fibers. Regional differences in the density of DBH-immunoreactive fibers were also present in squirrel monkey prefrontal cortex. Despite the regional variations in the density of DBH-immunoreactive fibers, the laminar distribution of these fibers was very similar across cytoarchitectonic areas of cynomolgus prefrontal cortex. Layer I contained a low density of labeled fibers which were primarily tangential in orientation. The predominantly radially oriented fibers in layers II-IV were slightly higher in density. The density of both radially and tangentially oriented immunoreactive fibers increased substantially in layer V. Fiber density decreased in layer VI; a band of tangentially oriented fibers was present in the deep portion of this layer. With a few exceptions, the laminar distribution of DBH-immunoreactive fibers in the prefrontal regions of squirrel monkey cortex was similar to that of cynomolgus monkey. Since other data suggest that anti-DBH selectively labels noradrenergic axons in monkey neocortex, the distinctive innervation patterns exhibited by DBH-immunoreactive fibers reveal the regions and layers that may be the principal sites of action of norepinephrine in exerting its effects on prefrontal cortical function.

Animals↗

PubMed1989

Monoclonal antibody to neurofilament protein (SMI-32) labels a subpopulation of pyramidal neurons in the human and monkey neocortex.

A monoclonal antibody that recognizes a nonphosphorylated epitope on the 168 kDa and 200 kDa subunits of neurofilament proteins has been used in an immunohistochemical study of cynomolgus monkey (Macaca fascicularis) and human neocortex. This antibody, SMI-32, primarily labels the cell body and dendrites of a subset of pyramidal neurons in both species. A greater proportion of neocortical pyramidal neurons were SMI-32 immunoreactive (ir) in the human than in the monkey. SMI-32-ir neurons exhibited consistent differences in the intensity of their immunoreactivity that correlated with cell size. The cellular specificity of SMI-32 immunoreactivity suggests that a subpopulation of neurons can be distinguished on the basis of differences in the molecular characteristics of basic cytoskeletal elements such as neurofilament proteins. The size, density, and laminar distribution of SMI-32-ir neurons differed substantially across neocortical areas within each species and between species. Differences across cortical areas were particularly striking in the monkey. For example, the anterior parainsular cortex had a substantial population of large SMI-32-ir neurons in layer V and a near absence of any immunoreactive neurons in the supragranular layers. This contrasted with the cortical area located more laterally on the superior temporal gyrus, where layers III and V contained substantial populations of large SMI-32-ir neurons. Both areas differed significantly from the posterior inferior temporal gyrus, which was distinguished by a bimodal distribution of large SMI-32-ir neurons in layer III. Differences across human areas were less obvious because of the increase in the number of SMI-32-ir neurons. Perhaps the most notable differences across human areas resulted from shifts in the density of the larger SMI-32-ir neurons in deep layer III. A comparison between the species revealed that isocortical areas exhibited greater differences in their representation of SMI-32-ir neurons than primary sensory or transitional cortical areas. A comparison of distribution patterns of SMI-32-ir neurons across monkey cortical areas and data available on the laminar organization of cortical efferent neurons suggests that a common anatomic characteristic of this chemically identified subpopulation of neurons is that they have a distant axonal projection. Such correlations of cell biological characteristics with specific elements of cortical circuitry will further our understanding of the molecular and cellular properties that are critically linked to a given neuron's role in cortical structure and function.

Animals↗

PubMed1988

Synaptic organization of serotonin-immunoreactive fibers in primary visual cortex of the macaque monkey.

The macaque neocortex is very densely innervated by serotonin-containing fibers. The highest density of these fibers is in primary sensory regions such as the primary visual cortex. By using an antibody against serotonin, we analyzed the distribution and morphology of serotonin-immunoreactive fibers and synapses in the primary visual cortex of the adult cynomolgus monkey. In addition, we quantified the laminar distribution of labeled varicosities and the distances between varicosities in single fibers. While serotonin-immunoreactive fibers are found in all cortical layers, at least three bands of heightened density of innervation were readily recognized that were coincident with 1) layer IIIB to IVC alpha, 2) layer VA, and 3) layer VIB. Layer IVC alpha of area 17 contained more varicosities per unit area than any other sublayer. There was a high degree of variability in the intervaricosity distances along single fibers; more than half were longer than 10 microns. At the electron microscopic level, synaptic contacts were also observed throughout the entire thickness of area 17, with the highest frequency in layer IV. The labeled varicosities were packed with electron-lucent synaptic vesicles and formed synaptic complexes with small, but conspicuous, post-synaptic densities. Dendritic shafts were the most common postsynaptic target of the labeled synapses. Among these characteristically slender post-synaptic shafts, profiles with structural features of both spiny and smooth dendrites were observed. The small diameter of most of the postsynaptic dendrites indicated that distal dendrites were preferentially contacted by serotonin-immunoreactive varicosities. Although direct identification of the postsynaptic neurons will be required for complete characterization of this circuitry, the distribution of serotonin-immunoreactive varicosities suggests that serotoninergic interactions in the primary visual cortex of the cynomolgus monkey are directed predominantly at the distal dendrites of granular and infragranular neurons rather than at targets in the supragranular layers.

Animals↗

PubMed1988

The dopaminergic innervation of monkey prefrontal cortex: a tyrosine hydroxylase immunohistochemical study.

The distribution of tyrosine hydroxylase (TH)-immunoreactive fibers was characterized immunohistochemically in the prefrontal cortical regions of both Old World cynomolgus monkeys (Macaca fascicularis) and New World squirrel monkeys (Saimiri sciureus). In both species, differences in the density and/or laminar distribution of TH-labeled fibers were detected both across and within almost every prefrontal cytoarchitectonic region. In cynomolgus monkeys, areas 9 and 24 had the greatest density of TH-labeled fibers, areas 11, 12, 13 and 25 were of intermediate density, and areas 10 and 46 had the lowest density of immunoreactive fibers. Differences in fiber density within many of these regions were also consistently observed. On a laminar basis, the distribution of labeled fibers in a given area of cynomolgus prefrontal cortex was systematically related to the overall fiber density of that area. For example, in the lightly innervated fundus of the principal sulcus (area 46), labeled fibers were primarily present in layer I and layers V-VI, whereas in area 9, the most densely innervated region, TH-labeled fibers were present in all cortical layers. Similar regional differences in the density and laminar distribution of TH-immunoreactive fibers were also present in squirrel monkey prefrontal cortex. In previous studies, we have analyzed the regional and laminar distributions of fibers immunoreactive for TH and dopamine-beta-hydroxylase (DBH), a specific marker for noradrenergic cortical fibers, in multiple areas of cortex from both normal and locus ceruleus-lesioned animals. These comparisons, which have been confirmed in the present report, indicate that anti-TH and anti-DBH label distinct populations of axons in monkey neocortex, which presumably are dopaminergic and noradrenergic, respectively. Thus, the distribution of TH immunoreactivity described in the present report suggests that dopaminergic fibers are distributed in a very heterogeneous fashion in monkey prefrontal cortex. The distinctive innervation patterns exhibited by these fibers reveal the regions and layers that may be the principle sites of action of dopamine in exerting its effects on prefrontal cortical function.

Animals↗

PubMed1988

Development of somatostatin-containing neurons and fibers in the rat hippocampus.

Using a combination of in situ hybridization and immunohistochemistry, the development of somatostatin (SS)-containing neurons and fibers was examined in the rat dorsal hippocampus and dentate gyrus. The major development of this hippocampal peptidergic system occurs postnatally. At postnatal day 1 (P1), neurons containing SS mRNA are evident primarily in the stratum oriens, but also in the hilus of the dentate gyrus. Similar neurons are also immunoreactive for SS28 and SS28(1-12), suggesting a minimal lag in the transcription of SS mRNA and its translation into specific SS peptides. The number of SS neurons increases postnatally to P10, followed by a decrease in number in the adult. This transient change in the number of SS neurons coincides with dramatic changes in SS28(1-12)-immunoreactive fibers, which are initially present in the stratum lacunosum moleculare, with no significant immunoreactivity in the dentate gyrus. By P15, the molecular layer of the dentate gyrus is densely innervated, while similar immunoreactivity in the stratum lacunosum moleculare is greatly reduced. These data are consistent with a transient projection from the stratum oriens to the stratum lacunosum moleculare, which is replaced by a projection from the hilus to the molecular layer of the dentate gyrus as this structure matures.

Animals↗

PubMed1988

Brainstem dopaminergic neurons project to monkey parietal cortex.

In this study, retrograde transport of Fast blue was combined with tyrosine hydroxylase immunohistochemistry to reveal the presence of projections from both dopaminergic and non-dopaminergic neurons of the substantia nigra-ventral tegmental area to the parietal cortex of cynomolgus monkeys (Macaca fascicularis). These findings confirm the results of previous studies demonstrating the existence of a dopaminergic innervation of monkey parietal cortex.

Amidines↗

PubMed1988

Immunohistochemical and in situ hybridization analysis of the development of the rat somatostatin-containing neocortical neuronal system.

The chemical differentiation of somatostatin (SS) neurons in rat neocortex was characterized by molecular biochemical and morphological methods. Northern (RNA) blotting indicates that regional distribution of SS mRNA correlates with the known distribution patterns of SS-containing neurons in the adult, while similar analysis of poly (A)+ RNA isolated from telencephalon at various times postnatally shows an increase between P9 and P15, with a slight decrease in the adult. In situ hybridization with a probe specific to SS mRNA, and immunohistochemistry using antisera specific for the N-terminally extended form of SS, SS28, and SS28(1-12), were used to detect neocortical neurons containing this mRNA or its translation product. The appearance of SS mRNA is coincident with detectable immunoreactivity for SS peptides. The expression of the SS gene by cortical neurons occurs in two waves. From P1 to P11, hybridizing neurons are predominant below the cortical plate in the developing infragranular layers. Immunohistochemical analysis of immunoreactivity to SS28 reveals a significant development of this neocortical system by late gestation (E20). At this point SS28(1-12), the predominant SS form detected, is mainly in neurons of the subplate, with less detectable immunoreactivity in the intermediate zone and cortical plate. By P2, neurons in the subplate exhibit detectable SS28 and SS28(1-12). Although immunoreactive perikarya are no longer detectable at P2 in the cortical plate or marginal zone, a very dense plexus of SS28(1-12) fibers is seen in the subplate, marginal zone, and intermediate zone; relatively few immunoreactive fibers are found in the cortical plate. By P12, a dramatic shift occurs; a large supragranular population of these SS neurons is observed by both mRNA and antibody methods, as is a subsequent decrease in number in the adult. The shift in immunoreactivity occurs with supragranular SS28-containing neurons now prominent, and SS28(1-12)-containing neurons and fibers greatly diminished. The number of neurons containing SS mRNA or SS28 immunoreactivity decreases from P12 to adult, when these neurons exhibit a bilaminar distribution. Neurons immunoreactive for SS28(1-12) are now sparsely distributed throughout the cortex, while SS28(1-12) fibers densely innervate layers I and V/VI.

Age Factors↗

PubMed1988

Occupational skin diseases, United States. Results from the Bureau of Labor Statistics Annual Survey of Occupational Injuries and Illnesses, 1973 through 1984.

The overall incidence rates, numbers, and proportions of occupational skin diseases recorded in the Bureau of Labor Statistics Annual Survey of Occupational Injuries and Illnesses, from 1973 through 1984, were reviewed, and a detailed analysis of occupational skin diseases recorded in the 1984 Annual Survey was performed. Overall incidence rates and numbers of cases declined from 1973 through 1983, but increased slightly in 1984. The major industrial divisions of agriculture and manufacturing have consistently had the highest rates and numbers of cases, respectively; skin diseases have accounted for almost two thirds of all occupational illnesses within agriculture. In the 1984 Annual Survey, 11 industries were ranked in the "Top 15" for both incidence rates and numbers of cases, at the two-digit Standard Industrial Classification level. At the four-digit level for manufacturing, four industries were also ranked in the "Top 15" for both indexes. This analysis has identified industries toward which research efforts should be directed to characterize those occupational activities or exposures most responsible for these higher risks.

Absenteeism↗

PubMed1988

Noradrenaline- and vasoactive intestinal peptide-containing neuronal systems in neocortex: functional convergence with contrasting morphology.

Neurotransmitter-specific anatomical techniques have provided a tool to define the morphological constraints within which a given neurotransmitter will exert its cellular actions. Biochemical and electrophysiological approaches have revealed the nature of these cellular actions for several neurotransmitters. Furthermore, by using purified preparations and tissue cultures a certain degree of resolution has been achieved by which the cell type, where a neurotransmitter's effect takes place, can be determined. In this article we review these aspects for noradrenaline and vasoactive intestinal peptide, two neurotransmitters of the cerebral cortex contained within neuronal systems that present strikingly different morphologies. Nevertheless, noradrenaline and vasoactive intestinal peptide share certain cellular actions and can interact synergistically. The experimental evidence accumulated to date indicates that noradrenaline- and vasoactive intestinal peptide-containing neurons can influence three general cell types of the cerebral cortex, i.e. (i) other neurons, (ii) astrocytes and (iii) cells of the vasculature. This diversity in cellular partners supports the notion that noradrenaline and vasoactive intestinal peptide can be released from neurons at conventional synapses as well as at extrasynaptic sites, thus suggesting the co-existence of two modes of release within the same neuron.

Cerebral Cortex↗

PubMed1988

Differential regulation of amyloid-beta-protein mRNA expression within hippocampal neuronal subpopulations in Alzheimer disease.

We have mapped the neuroanatomical distribution of amyloid-beta-protein mRNA within neuronal subpopulations of the hippocampal formation in the cynomolgus monkey (Macaca fascicularis), normal aged human, and patients with Alzheimer disease. Amyloid-beta-protein mRNA appears to be expressed in all hippocampal neurons, but at different levels of abundance. In the central nervous system of monkey and normal aged human, image analysis shows that neurons of the dentate gyrus and cornu Ammonis fields contain a 2.5-times-greater hybridization signal than is present in neurons of the subiculum and entorhinal cortex. In contrast, in the Alzheimer disease hippocampal formation, the levels of amyloid-beta-protein mRNA in the cornu Ammonis field 3 and parasubiculum are equivalent. These findings suggest that within certain neuronal subpopulations cell type-specific regulation of amyloid-beta-protein gene expression may be altered in Alzheimer disease.

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PubMed1988

Distribution of precursor amyloid-beta-protein messenger RNA in human cerebral cortex: relationship to neurofibrillary tangles and neuritic plaques.

Neurofibrillary tangles (NFT) and neuritic plaques (NP), two neuropathological markers of Alzheimer disease, may both contain peptide fragments derived from the human amyloid beta protein. However, the nature of the relationship between NFT and NP and the source of the amyloid beta proteins found in each have remained unclear. We used in situ hybridization techniques to map the anatomical distribution of precursor amyloid-beta-protein mRNA in the neocortex of brains from three subjects with no known neurologic disease and from five patients with Alzheimer disease. In brains from control subjects, positively hybridizing neurons were present in cortical regions and layers that contain a high density of neuropathological markers in Alzheimer disease, as well as in those loci that contain NP but few NFT. Quantitative analyses of in situ hybridization patterns within layers III and V of the superior frontal cortex revealed that the presence of high numbers of NFT in Alzheimer-diseased brains was associated with a decrease in the number of positively hybridizing neurons compared to controls and Alzheimer-diseased brains with few NFT. In contrast, no correlation was found between the densities of NP and neurons containing precursor amyloid-beta-protein mRNA transcripts. These findings suggest that the expression of precursor amyloid-beta-protein mRNA may be a necessary but is clearly not a sufficient prerequisite for NFT formation. In addition, these results may indicate that the amyloid beta protein, present in NP in a given region or layer of cortex, is not derived from the resident neuronal cell bodies that express the mRNA for the precursor protein.

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