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T G Beach

Publications and source records attributed to T G Beach.

14 recordsLinked to original sources

Cholinergic fiber loss occurs in the absence of synaptophysin depletion in Alzheimer's disease primary visual cortex.

The significance of cholinergic degeneration in Alzheimer's disease (AD) depends, in part, on whether it is an early event, possibly integral to the progression of the disease, or a late event, occurring only as a secondary effect of cortical degeneration. We have been studying the primary visual cortex in AD cases, on the assumption that the disease process may be retarded in this relatively-spared area, thus providing a 'window' on early AD. In this work, we have quantified acetylcholinesterase fiber density and the density of an immunohistochemical reaction for synaptophysin as measures of cholinergic and total synaptic loss, respectively, in the primary visual cortex of AD and control cases. Cholinergic fibers were depleted to 15% of control values, while synaptophysin density was not significantly altered. Cholinergic degeneration thus appears to occur in the absence of generalized synaptic loss in this area.

Acetylcholinesterase

Senile plaques, amyloid beta-protein, and acetylcholinesterase fibres: laminar distributions in Alzheimer's disease striate cortex.

The laminar distributions of senile plaques and amyloid beta-protein (A beta P) within the striate cortex of patients with Alzheimer's disease (AD) were studied with enhanced Bielschowsky (roughly equivalent to the Campbell technique) and immunohistochemical methods. The laminar distribution of acetylcholinesterase (AChE) fibres within the striate cortex of both AD patients and control patients was studied with an enzyme histochemical method. Quantification of Bielschowsky-stained plaque numbers along intersect lines drawn parallel to laminar boundaries revealed a significant aggregation of plaques at the interface of layers IVc and V. Lines drawn through layer VI intersected significantly fewer plaques than lines through other laminae. Immunoperoxidase staining for A beta P revealed a similar distribution of senile plaques, and addition, prominent, diffuse deposits of A beta P within layers I and IVc. AChE fibres were markedly depleted in the striate cortex of AD cases. In control cases, AChE fibres were, like A beta P immunoreactivity, concentrated within layer I and IVc. The results indicate that enhanced silver methods may not reveal the complete distribution of A beta P. The codistribution of A beta P-immunoreactive diffuse amyloid deposits and AChE fibres to the same cortical laminae is consistent with the possibility that these deposits may be formed from degenerating cholinergic elements. The formation of a line of senile plaques at the interface of two cortical laminae within the striate cortex, in an anatomically analogous situation to a similar line of plaques within the dentate gyrus, suggests that formation of well-defined plaques may be accelerated by the interaction of specific neuronal systems.

Acetylcholinesterase

An animal model of prophylactic cranial irradiation: histologic effects at acute, early and delayed stages.

Wistar rats (body wt. 200 g) were subjected to a fractionated course of radiation similar to that used in prophylactic brain irradiation for small cell carcinoma of the lung (2000 cGy in 5 fractions over 5 days with 60Co). Effects of this regimen were assessed by histologic examination of brain sections at 1 week, 1 month and 6 months post-irradiation. With conventional stains there were no apparent differences between control and irradiated brains at any of the post-irradiation intervals. Immunohistochemistry for neurotransmitter synthetic enzymes tyrosine hydroxylase and glutamate decarboxylase, as well as histochemistry for acetylcholinesterase, failed to uncover any changes in the irradiated animals. Immunohistochemistry for glial fibrillary acidic protein, an astrocyte marker, also showed no differences in the irradiated groups. However, an antibody against a major histocompatibility complex, class II antigen (OX-6) revealed a microglial response in grey and white matter beginning at 1 month and increasing up to the 6 month post-irradiation interval. The neuroanatomical basis for this microglial response was suggested by the results of silver stains for nerve axons, which revealed axonal loss in striatal white matter bundles in a pattern implicating vascular insufficiency.

Acetylcholinesterase

Lamina-selective A68 immunoreactivity in primary visual cortex of Alzheimer's disease patients.

Sections of area 17 from 9 Alzheimer's disease (AD) and 13 control cases were stained using the monoclonal antibody, Alz-50, which identifies pathologically-involved neuronal systems in AD patients. Strong positive staining was seen only in AD cases. The pattern of staining was highly lamina-selective; laminae I-IVa and V were intensely stained and lamina VI staining was moderately intense, while laminae IVb and IVc were relatively unstained. The results support the growing consensus that cortical pathology in AD is not generalized, but affects specific neuronal populations. The specific anatomical distribution of degenerative change suggests that there may be a specific set of visual deficits in AD patients.

Adolescent

Patterns of gliosis in Alzheimer's disease and aging cerebrum.

The distribution of astrocytic gliosis in Alzheimer's disease (AD) and aging cerebrum, as marked by immunoperoxidase staining for glial fibrillary acidic protein (GFAP), was examined in whole-hemisphere coronal sections. Cortical gliosis in AD had an obvious laminar pattern. There were two heavy bands of staining, one in layers II-III and another in layer V. Normal aging cases sometimes displayed considerable cortical gliosis, but no specific patterns were apparent. Most AD cases, and some normal aging cases, displayed hypertrophy of immunoreactive astrocytes at grey matter-white matter interfaces, especially the cortico-medullary junction. Subcortical grey matter gliosis was common in both normal aging and AD, but there was no consistent pattern in either group. The deep cerebral white matter, which is stained evenly and heavily in young, healthy individuals, showed uneven staining in both normal elderly and AD brains. In both AD and aging, perivascular gliosis was prominent throughout the cerebrum and especially in the putamen. In conclusion, both AD and aging cerebri show extensive gliosis: AD cortical gliosis has a specific laminar pattern, but there does not appear to be an AD-specific pattern of subcortical gliosis.

Adult

Lamina-specific arrangement of astrocytic gliosis and senile plaques in Alzheimer's disease visual cortex.

Alzheimer's disease (AD) visual cortex (area 17) was investigated using stains for plaques and tangles (Bielschowsky, thioflavine S) and gliosis (GFAP immunoperoxidase). Pathology was heaviest in layers II, III, IVa and IVc. Of especial interest was a thin line of plaques and astrocytic gliosis at the lower margin of layer IVc. These results could provide an insight into the pathogenesis of AD, and suggest that patients with AD may have specific visual deficits.

Aged

Retrograde filling of pyramidal neurons in postmortem human cerebral cortex using horseradish peroxidase.

A method for retrograde filling of neurons in the postmortem human brain is described. Fresh human brains with minimal postmortem delay (3-11 h) were used. Horseradish peroxidase (HRP) crystals were applied directly to white matter underlying the cerebral cortex. After 5 min, the HRP was washed off and the tissue incubated in the cold for 24-48 h prior to frozen sectioning and development with 3,3'-diaminobenzidine. Reaction product filled pyramidal neurons and fibers in laminae V and VI. The method appears to be useful for labelling cortical projection neurons and cortical afferent fibers and should be applicable to other brain areas.

Aged

Tract-tracing with horseradish peroxidase in the postmortem human brain.

A method for tracing central nervous system fiber tracts in the postmortem human brain is described. Fresh human brains with minimal postmortem delay (3-7 h) were used. Horseradish peroxidase (HRP) crystals were applied directly to the cross-sectioned face of the left dorsal columns at cervical spinal cord or caudal medullary levels. After 5 min, the HRP was washed off and the brainstem incubated in the cold for 24-48 h prior to sectioning and developing with diaminobenzidine. Reaction product was observed in nerve fibers of the ipsilateral dorsal columns, dorsal horn and the nuclei cuneatus and gracilis, up to 2.0 cm from the application point. The method should be useful for tract-tracing throughout the human brain.

3,3'-Diaminobenzidine

Light microscopic evidence for a substance P-containing innervation of the human nucleus basalis of Meynert.

A two color histochemical/immunohistochemical method was used to demonstrate substance P and acetylcholinesterase in sections of the human nucleus basalis of Meynert (nbM). Substance P-immunoreactive terminal-like structures were found to make contact with magnocellular, acetylcholinesterase-positive perikarya and primary dendrites throughout all subdivisions of the nbM. This apparent innervation of nbM neurons was in most cases a relatively sparse one, but a small percentage of these neurons appeared to be recipients of a very heavy innervation which covered their perikarya and primary dendrites.

Acetylcholinesterase

Perfusion-fixation of the human brain for immunohistochemistry: comparison with immersion-fixation.

A method of perfusion-fixation of the human brain is described and compared with immersion-fixation by immunoperoxidase staining for several substances (tyrosine hydroxylase, substance P, choline acetyltransferase, glutamate decarboxylase, Met-enkephalin, and neuron-specific enolase) in human striatum. Results from 1-cm slices fixed by immersion for 1, 2, 4 and 8 days were compared with results from slices of perfused brain postfixed for the same time periods. The fixative used in all steps was 4% paraformaldehyde at 4 degrees C. In the immersion-fixed brains, optimal immunoreaction for tyrosine hydroxylase and glutamate decarboxylase was limited to a depth of 1-2 mm from the surface of the brain slice. In contrast, staining density in perfusion-fixed brains was relatively homogeneous and of high quality. The other antigens studied displayed more uniform staining throughout the section with both perfused and immersed brains. Investigators intending to study human brain immunohistochemistry using immersion-fixation should be aware of the possibility of depth-related variations in staining intensity and would be wise to determine whether this effect is significant for the antigens they choose to study.

Aged

The distribution of substance P in the primate basal ganglia: an immunohistochemical study of baboon and human brain.

Using immunohistochemical methods we have studied the distribution of substance P fibers, terminals and perikarya throughout the basal ganglia of baboons and at selected levels of the human brain. Immunoreactivity in the substantia nigra pars reticulata, internal segment of the globus pallidus and ventral pallidum was dense and of a characteristic, "woolly-fiber" morphology. The caudate nucleus and putamen contained sharply circumscribed patches of dense immunoreactivity superimposed on a moderately stained background. The external division of the globus pallidus displayed very little immunoreactivity. Two morphological types of immunoreactive cell bodies were present in the caudate nucleus, putamen and nucleus accumbens, and were clustered within the dense patches. The distribution of immunoreactive perikarya within the striatum differed from that reported for rats, as immunoreactive neurons were distributed evenly throughout the rostrocaudal extent rather than being concentrated in the rostral portions.

Animals

Neocortical substance P neurons in the baboon: an immunohistochemical finding.

Substance P-like immunoreactive (SP-LI) neurons have been demonstrated, by an avidin-biotin immunohistochemical method, in several neocortical areas in the brains of baboons. These neurons are mostly small in size, and are of many different somatic shapes, including bipolar and multipolar types. They occur in laminae III-VI but are most common in laminae V and VI. It is postulated that these neurons could contribute to previously-described cortical SP-LI fiber networks.

Animals