A comparative study of histological and immunohistochemical methods for neurofibrillary tangles and senile plaques in Alzheimer's disease.

Several studies have demonstrated that the accurate visualization and quantification of pathological lesions in neurodegenerative disorders depend on the reliability of staining methods. In an attempt to gain a better assessment of the density and distribution of the neuropathological markers of Alzheimer's disease, we compared the staining efficiency of a modified thioflavine S protocol for neurofibrillary tangles (NFT) and senile plaques (SP) to different argentic impregnation techniques (Bielchowsky, Gallyas, Globus, Campbell-Switzer-Martin) and to immunohistochemical stainings obtained with two different antibodies against the amyloid beta protein A4 and the microtubule-associated tau protein. The modified thioflavine S technique (MTST) detects up to 60% more SP and up to 50% more NFT than the Bielschowsky and Globus methods, respectively.

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.

Asymmetric increase in substance P immunoreactivity in the rat and guinea pig substantia nigra after unilateral neocortical ablation.

Substance P was visualized in the rat and the guinea pig basal ganglia, mesencephalon and spinal cord after surgical unilateral cortical ablation. An increased density in substance P-like immunoreactive patterns in the substantia nigra was observed ipsilaterally to the lesioned hemisphere. These results, together with previous observations in cases of Alzheimer's disease presenting with asymmetric cortical atrophy, suggest an influence of the corticostriatal pathway on substance P-like immunoreactivity in these subcortical structures.

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.

Parvalbumin in the monkey striate cortex: a quantitative immunoelectron-microscopy study.

Parvalbumin (PV) is present in a subpopulation of interneurons in the visual cortex, and also in thalamic afferents to the neocortex of primates. The object of this study is to confirm by immunoelectron-microscopy the presence of intrinsic and extrinsic connections containing parvalbumin in the monkey visual cortex, by the demonstration of parvalbumin-immunoreactivity in symmetric and asymmetric synapses. We analyzed the distribution of parvalbumin-immunoreactive profiles at the ultrastructural level in the primary visual cortex of old world monkeys (Macaca fascicularis).

Parvalbumin-immunoreactive neurons in the neocortex are resistant to degeneration in Alzheimer's disease.

Recent studies have stressed the fact that specific neuronal subtypes may display a differential sensitivity to degeneration in Alzheimer's disease. For example, large pyramidal neurons have been shown to be vulnerable, whereas smaller neurons are resistant to pathology. Using a monoclonal antibody against the calcium-binding protein parvalbumin, we investigated the possible changes in a subpopulation of interneurons in two cortical areas known to be strongly damaged in Alzheimer's disease.

Vasoactive intestinal peptide binding sites and fibers in the brain of the pigeon Columba livia: an autoradiographic and immunohistochemical study.

The distribution of vasoactive intestinal peptide (VIP) binding sites in the pigeon brain was examined by in vitro autoradiography on slide-mounted sections. A fully characterized monoiodinated form of VIP, which maintains the biological activity of the native peptide, was used throughout this study. The highest densities of binding sites were observed in the hyperstriatum dorsale, archistriatum, auditory field L of neostriatum, area corticoidea dorsolateralis and temporo-parieto-occipitalis, area parahippocampalis, tectum opticum, nucleus dorsomedialis anterior thalami, and in the periventricular area of the hypothalamus.

Neocortical neuronal subpopulations labeled by a monoclonal antibody to calbindin exhibit differential vulnerability in Alzheimer's disease.

Numerous studies have demonstrated that specific neuronal subtypes display a differential vulnerability to the pathological process in Alzheimer's disease. Large pyramidal neurons are likely to be highly vulnerable, whereas smaller neurons are more resistant to pathology. Using a monoclonal antibody to the calcium-binding protein calbindin, we observed in the human prefrontal cortex distinct populations of labeled cells.

A subpopulation of primate corticocortical neurons is distinguished by somatodendritic distribution of neurofilament protein.

In recent immunohistochemical studies of human and monkey neocortex we observed that the somatodendritic distribution of neurofilament protein appears to be restricted to a subpopulation of pyramidal neurons. To further characterize this apparent specificity in cytoskeletal organization, combined retrograde tract tracing and immunohistochemical methods were used to examine the extent to which neurons from different cortical areas providing a projection to prefrontal cortex have a somatodendritic distribution of neurofilament proteins. These studies revealed that the proportion of neurons providing a projection from different cortical areas to prefrontal cortex varied from nearly 30% to 90%, and appeared to be related to the functional nature of the projection.

Object recognition deficit in Alzheimer's disease: possible disconnection of the occipito-temporal component of the visual system.

An early object recognition impairment was observed in a patient presenting with a slowly progressive Alzheimer's disease. At autopsy, the cerebral cortex showed increased neuritic plaque and neurofibrillary tangle counts, particularly in the occipital and temporal lobes as compared to Alzheimer's disease cases with the usual clinical presentation and distribution of the neuropathological lesions (i.e.

An anatomic substrate for visual disconnection in Alzheimer's disease.

During a recent clinical and neuropathologic evaluation of a large population of brains collected at autopsy, attention was drawn to a subset of Alzheimer's disease (AD) patients presenting with prominent visual symptomatology as the first sign of the disease. In this population, a shift in the distribution of pathologic profiles had occurred such that the primary visual areas and the visual association areas 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 neuropathologic hallmarks of the disease, neurofibrillary tangles and neuritic plaques.

Neuropathological observations in a case of autism presenting with self-injury behavior.

We report the neuropathological evaluation of a 24-year-old autistic woman suffering from a residual state of infantile autism and presenting with self-injury behavior since childhood. Her behavior included head-banging, eye-gouging and self-biting. All intended therapeutic measures remained without effect, including high doses of psychotropic drugs.

Distribution of parvalbumin immunoreactivity in the visual cortex of Old World monkeys and humans.

The macaque visual system has been frequently used as a model for understanding functional aspects of human vision. There are, however, few studies directly comparing biochemically defined neuronal populations in the visual cortex of the two species. In this study we compared the distribution and morphological features of the parvalbumin-immunoreactive neuronal subpopulation within humans and Old World monkeys (Macaca fascicularis and Macaca mulatta) by using monoclonal antibodies against the Ca2(+)-binding protein parvalbumin (PV), a neuronal marker in the vertebrate cerebral cortex.

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.

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.

Autoradiographic analysis of the distribution of vasoactive intestinal peptide binding sites in the vertebrate central nervous system: a phylogenetic study.

The distribution of vasoactive intestinal peptide (VIP) binding sites in the brain of several vertebrate species was examined by in vitro autoradiography on slide-mounted sections. This study included fish, frog, snake, pigeon, rat, mouse, guinea pig, cat and monkey brain. A fully characterized, monoiodinated form of vasoactive intestinal peptide (M-125I-VIP), which maintains the biological activity of the native peptide in the central nervous system (CNS), was used throughout the study.

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.

Substance P immunoreactivity in Alzheimer disease: a study in cases presenting symmetric or asymmetric cortical atrophy.

Substance P-like immunoreactivity was visualized by immunohistochemical methods in 20 postmortem brains: 6 senile, 4 presenile Alzheimer dementia (AD), 3 AD with interhemispheric asymmetric cortical atrophy, and 7 control cases. For all pathological cases, the SP-like immunoreactivity was significantly reduced in the neocortical areas and in the hippocampus. This contrasted with an enhanced SP-like immunoreactivity in the pallidum and the substantia nigra in AD brains and a more pronounced SP-like immunoreactivity in the more atrophic side in the asymmetrically atrophied brains.

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.

Age-dependent supersensitivity to the glycogenolytic effect of K+ in the cerebral cortex of the spontaneously epileptic quaking mouse mutant.

K+, at concentrations reached in the extracellular space during neuronal activity (5-10 mM), promotes a time- and concentration-dependent hydrolysis of [3H]glycogen newly synthesized by mouse cerebral cortical slices. In the present study, the glycogenolytic action of K+ was examined in the neocortex of the quaking mouse, a spontaneously epileptic mutant characterized by deficient myelination of the CNS. The potency and efficacy of K+ in eliciting glycogen hydrolysis was greatly enhanced in cerebral cortical slices prepared from homozygous quaking mice (qk/qk) older than 7 weeks of age, indicating a supersensitive response to a metabolic action of the ion.

High- and low-affinity binding sites for vasoactive intestinal peptide (VIP) in the rat kidney revealed by light microscopic autoradiography.

The distribution of VIP binding sites in rat kidney and adrenal gland has been examined by light microscopic autoradiography. A fully characterized mono-iodinated molecular form of VIP (M-125-I-VIP) which maintains the biological activity of the native peptide, was used for this study. Two types of VIP binding sites, with high and low affinity, have been identified.

K+ at concentrations reached in the extracellular space during neuronal activity promotes a Ca2+-dependent glycogen hydrolysis in mouse cerebral cortex.

The effect of increasing [K+]0 on 3H-glycogen levels was examined in mouse cerebral cortical slices. K+ stimulates in a time- and concentration-dependent manner the hydrolysis of 3H-glycogen. Over 70% of the maximal effect is reached within 30 sec and the EC50 for the glycogenolytic action of K+ is 11 mM.

Autoradiographic mapping of [mono[125I]iodo-Tyr10, MetO17]vasoactive intestinal peptide binding sites in the rat brain.

The distribution of vasoactive intestinal peptide binding sites in the rat brain was examined by in vitro autoradiography on slide-mounted sections. A fully characterized monoiodinated form of vasoactive intestinal peptide (M-[125I]VIP) previously shown to maintain in the central nervous system the full biological activity of native vasoactive intestinal peptide was used for this study. In initial kinetic and pharmacological experiments the binding of M-[125I]vasoactive intestinal peptide to slide-mounted sections was shown to be time-dependent, saturable and reversible.