Age versus ageing as a cause of dementia.
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Biomedical subjects
C Bouras
Publications and source records attributed to C Bouras.
Vasopressin binding in the cerebral cortex of the Mongolian gerbil is reduced by transient cerebral ischemia.
In Mongolian gerbils, the content of vasopressin in the cerebral cortex, the striatum, and the hypothalamus is increased after induction of acute cerebral ischemia. We used an iodinated vasopressin analogue and light microscopic autoradiography to study the distribution of vasopressin V1 receptors in the brain of adult male gerbils and to evaluate the effects of a transient bilateral cerebral ischemia (6 minutes) on the density of this receptor population. The animals were killed immediately or 10, 30, or 100 hours after transient bilateral occlusion of the common carotid arteries. In control animals, specific [125I]-VPA binding sites were present in various structures of the brain (olfactory bulb, anterior olfactory nucleus, lateral septum, bed nucleus of the stria terminalis, median preoptic area, ventral pallidum, substantia innominata, amygdala, thalamus, hypothalamic mammillary nuclei, superior colliculus, subiculum, central gray, nucleus of the solitary tract, hypoglossal nucleus). The strongest labeling was detected in the cerebral cortex, layers 5-6. After 30-100 hours of survival time following ischemia there was a marked decrease in [125I]-VPA binding site density in these cerebral cortex layers. To a lesser degree, a decrease was also detected in the lateral septal nucleus. In contrast, labeling in other noncortical structures remained unchanged. All animals with 100 hours recovery showed a loss of cells in hippocampus (CA1 layer) and striatum. In addition, ischemia induced concomitant and proliferative changes in cortical and hippocampal astrocytes assessed by glial fibrillary acid protein immunoreactivity. These observations indicate a role for vasopressin in the cerebral cortex either on neurons or on glial cells and the modulation of vasopressin receptor expression by transient cerebral ischemia.
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Localization of noradrenaline transporter mRNA expression in the human locus coeruleus.
The distribution of the noradrenaline transporter mRNA was examined in the human dorsolateral pontine tegmentum, using in situ hybridization histochemistry with 35S-labeled oligonucleotide probes. Analysis of film autoradiograms showed that noradrenaline transporter mRNA was expressed through the whole extent of the locus coeruleus complex. The largest population of labeled cells was seen in the nucleus locus coeruleus proper whereas few scattered labeled cells were visualized in its ventral subdivision, namely the locus subcoeruleus area. Thus, these anatomical findings suggest that cells expressing noradrenaline transporter mRNA in the human brainstem are predominantly, if not exclusively, concentrated within areas known to contain the largest collections of noradrenergic neurons.
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Age-related distribution of neuropathologic changes in the cerebral cortex of patients with Down's syndrome. Quantitative regional analysis and comparison with Alzheimer's disease.
OBJECTIVE: To investigate whether changes in the cerebral cortex exhibit similar distribution patterns in both disorders of Down's syndrome and Alzheimer's disease, we performed a comparative neuropathologic study of patients with these disorders to further clarify the possible relationships between these dementing conditions. DESIGN: The regional and laminar distribution and density of neurofibrillary tangles and senile plaques were analyzed in the cerebral cortex of a series of 16 patients (aged 6 to 74 years) with Down's syndrome and in 10 elderly individuals with Alzheimer's disease. RESULTS: Quantitative analyses revealed that the time course of neurofibrillary tangle formation in Down's syndrome displays regional patterns comparable with those observed in aging and Alzheimer's disease with layer II of the entorhinal cortex being affected first in Down's syndrome, followed by the hippocampus proper and neocortex. The oldest patients with Down's syndrome had neurofibrillary tangle densities sometimes higher than in patients with Alzheimer's disease. At variance with Alzheimer's disease, amyloid deposition was widespread in all of the cortical areas investigated and was observed much earlier than neurofibrillary tangle formation. Patients with Down's syndrome also frequently had higher senile plaque densities than patients with Alzheimer's disease. CONCLUSIONS: These results indicate that the development of pathologic changes in patients with Down's syndrome does not parallel that observed in elderly individuals and patients with Alzheimer's disease in all respects. However, the comparable development patterns of neurofibrillary tangle formation suggest that detailed analysis of patients with Down's syndrome may be useful to further our knowledge of the mechanisms underlying the installation of the neuropathologic alterations leading to the demonstrated loss of select neuronal populations in Alzheimer's disease.
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Regional distribution of neurofibrillary tangles and senile plaques in the cerebral cortex of very old patients.
OBJECTIVES: To examine the correlations between senile lesion densities and development of dementia symptoms in very old people. To perform a quantitative neuropathologic evaluation of several cortical and subcortical areas in a series of 29 nonagenarians and centenarians. PATIENTS: Ten patients with no cognitive impairment and 19 patients with clinically overt Alzheimer's disease. DESIGN: Neuropathologic case series. Severity of Alzheimer's disease was assessed with the Mini-Mental State examination and by postmortem chart review using the extended Clinical Dementia Rating Scale. Comparisons between neurofibrillary tangle and senile plaque densities in demented and nondemented individuals were performed by analysis of covariance controlling for age at the time of death. SETTING: Studies were conducted at the Psychiatric and Geriatric hospitals of the University of Geneva School of Medicine in Geneva, Switzerland. MAIN OUTCOME MEASURE: Correlations between clinical diagnosis and severity of Alzheimer's disease and neuropathologic change densities. RESULTS: Statistically significant differences were found in neurofibrillary tangle densities in the superior parietal, superior temporal, anterior and posterior cingulate cortex, and nucleus basalis of Meynert between nondemented and Alzheimer's disease cases. The superior parietal and posterior cingulate cortex contained significantly higher senile plaque counts in demented compared with nondemented cases. In contrast to younger demented cases, the number of senile plaques in the neocortex was correlated with the severity of dementia in centenarians. CONCLUSIONS: These results indicate that the neuronal degeneration in very old demented patients involves cortical areas usually preserved at the early stages of the dementing process. Senile plaque formation in certain neocortical areas may be a pathologic hallmark of the severity of dementia in this particular age group.
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Dementia lacking distinctive histopathology: clinicopathological evaluation of 32 cases.
We report the neuropathological findings in 32 patients, aged 46-86 years, with dementia lacking distinctive histopathology. All of the patients were classified clinically as having Pick's or atypical Pick's disease, but the routine neuropathological evaluation showed no specific histopathological changes such as Pick bodies, senile plaques, neurofibrillary tangles or Lewy bodies. In 50% of the cases the first symptoms appeared before 65 years of age. However, there were 9 patients with onset in the eighth decade. Positive family history was found only in 6 presenile cases. The retrospective evaluation of the clinical records revealed the consistent presence of "frontal" symptomatology, including loss of personal awareness, inappropriate euphoria and stereotyped behavior. Speech disorders were observed in 80% of the cases, whereas temporospatial disorientation and memory impairment were less frequent. Praxis and gnosis were strikingly preserved in most of the cases. The macroscopic neuropathological examination revealed frontal or temporopolar atrophy in 97% of the cases, while the hippocampus and subcortical structures were relatively spared in the majority of the cases. Histologically, four groups were recognized. Group A showed moderate to severe neuron loss and gliosis in the frontal and/or temporopolar cortex without subcortical involvement. In group B, the neocortical cell loss was widespread, and the striatum and substantia nigra displayed differential degrees of gliosis but no neuron loss. Group C patients showed a lesion distribution comparable to that observed in group B but with severe neuron loss in at least one subcortical region. Four cases formed group D, which was characterized by the preservation of the pyramidal neurons in the neocortex and variable subcortical changes. Despite these differences in the topography of pathological changes, all of the cases shared a similar clinical profile. These findings further demonstrate the epidemiological and neuropathological heterogeneity of dementia lacking distinctive histopathology. Furthermore, they suggest that the same clinical manifestations may correspond to several distinct pathological processes in this condition.
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Quantitative analysis of neuropathologic changes in the cerebral cortex of centenarians.
1. The quantitative distribution of neurofibrillary tangles and senile plaques was studied in the brains of 65 elderly patients aged from 96 to 104 years by immunohistochemistry. 2. According to the clinical and neuropathological diagnoses, three groups of cases were considered: 19 patients with Alzheimer's disease, 22 patients with mixed dementia (vascular and degenerative) and 24 patients with no or very mild cognitive impairment. 3. Moderate to high neurofibrillary tangle densities were always present in the hippocampus and entorhinal cortex. The inferior temporal cortex was very frequently affected in demented and non-demented cases whereas the superior frontal cortex was spared in the majority of cases independently of the clinical diagnosis. Quantitatively, Alzheimer's disease cases showed significantly higher NFT densities than cases with no clinical findings of dementia only in the CA1 field of the hippocampus. 4. The hippocampus and entorhinal cortex were often devoid of senile plaques in non-demented cases while the vast majority of Alzheimer's disease cases had few SP in these regions. The frontal and temporal cortex were more frequently involved than the limbic structures in both non-demented and Alzheimer's disease cases. The SP densities in layers II and III of the inferior temporal and superior frontal cortex were significantly higher in Alzheimer's disease than in non-demented cases. 5. These observations suggest that the dementing process in nonagenarians and centenarians may differ to that described in younger demented individuals in that neurofibrillary tangles involve principally the hippocampal formation with relative sparing of the neocortex. Furthermore, they indicate that both the neurofibrillary tangle densities in the CA1 field and senile plaque densities in the superficial layers of the neocortex must be considered for the neuropathological diagnosis of Alzheimer's disease in this age group.
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[3H]Nisoxetine binding sites in the cat brain: an autoradiographic study.
The binding of [3H]nisoxetine, a selective inhibitor of the high-affinity noradrenaline uptake sites, was studied on frontal frozen sections of the cat brain. The highest densities in autoradiographic signal were observed in the nucleus locus coeruleus and its ascending pathways, in the area postrema and in the dorsal part of the inferior olive, the pontine nuclei, the raphe nuclei, the colliculi, the periventricular and lateral areas of the hypothalamus, the suprachiasmatic nucleus, the nucleus accumbens and the olfactory bulb. A moderately high concentration of binding sites was observed in the hippocampal formation, especially in the molecular layer of Ammon's horn, in the superficial layers of the entorhinal cortex and in the indusium griseum. Binding sites were visualized in all the subdivisions of the neocortex. The highest density of binding was generally detected in the outer edge of the superficial layer I. In some cortical areas, especially in the visual cortex, labeling with a prevalent laminar distribution in the superficial layers I-III and in the deep layers V-VI was clearly observed. Moderate to low densities of binding sites were seen in most other areas of the brain except in the white matter, the caudate nucleus and putamen, which were devoid of labeling. Overall these findings indicate a good correlation between the distribution of [3H]nisoxetine binding sites and the noradrenergic systems. Furthermore, data suggest that in several areas, high-affinity noradrenaline reuptake mechanisms could play an important role in local interactions between the noradrenergic system and the other monoaminergic systems.
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Distribution of dopaminergic fibers and neurons in visual and auditory cortices of the harbor porpoise and pilot whale.
The distribution of putative dopaminergic fibers in two sensory cortical areas in the brain of the harbor porpoise (Phocoena phocoena) and pilot whale (Globicephala melaena) was analyzed at the light and electron microscopic levels using tyrosine hydroxylase (TH) immunohistochemistry. The quantitative analysis of the distribution of labeled fibers demonstrates that the primary visual cortex located in the lateral gyrus and entolateral sulcus contains a denser dopaminergic innervation than the auditory cortex within the posterior portion of the presylvian gyrus. In both areas, TH-immunoreactive fibers are densest in layer I, while layers IIIab and VI have intermediate densities and layers II and IIIc-V have the lowest fiber counts. Layer I is characterized by the presence of very thick TH-immunoreactive fiber populations, in addition to the thin and varicose fiber plexus observed throughout the cortical layers. Electron microscopic analyses demonstrated that some of these thick fibers represent the dendrites of TH-immunoreactive neurons located in the deep portion of layer I. The patterns observed in the present study suggest that the dopaminergic projections to the neocortex in whales have a different organization than in terrestrial mammals, particularly rodents and primates. These differences may reflect the fact that during evolution, the cetacean neocortex has retained many of the cytoarchitectonic features that are usually observed only in proisocortical regions in progressive terrestrial mammals.
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The iron-binding protein lactotransferrin is present in pathologic lesions in a variety of neurodegenerative disorders: a comparative immunohistochemical analysis.
Lactotransferrin is a glycoprotein that specifically binds and transports iron. This protein is also believed to transport other metals such as aluminum. Several lines of evidence indicate that iron and aluminum are involved in the pathogenesis of many dementing diseases. In this context, the analysis of the iron-binding protein distribution in the brains of patients affected by neurodegenerative disorders is of particular interest. In the present study, the distribution of lactotransferrin was analyzed by immunohistochemistry in the cerebral cortex from patients presenting with Alzheimer's disease, Down syndrome, amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam, sporadic amyotrophic lateral sclerosis, or Pick's disease. The results show that lactotransferrin accumulates in the characteristic lesions of the different pathologic conditions investigated. For instance, in Alzheimer's disease and Guamanian cases, a subpopulation of neurofibrillary tangles was intensely labeled in the hippocampal formation and inferior temporal cortex. Senile plaques and Pick bodies were also consistently labeled. These staining patterns were comparable to those obtained with antibodies to the microtubule-associated protein tau and the amyloid beta A4 protein, although generally fewer neurofibrillary tangles were positive for lactotransferrin than for tau protein. Neuronal cytoplasmic staining with lactotransferrin antibodies, was observed in a subpopulation of pyramidal neurons in normal aging, and was more pronounced in Alzheimer's disease, Guamanian cases, Pick's disease, and particularly in Down syndrome. Lactotransferrin was also strongly associated with Betz cells and other motoneurons in the primary motor cortex of control, Alzheimer's disease, Down syndrome, Guamanian and Pick's disease cases. These same lactotransferrin-immunoreactive motoneurons were severely affected in the cases with amyotrophic lateral sclerosis. It is possible that in these neurodegenerative disorders affected neurons either take up or synthesize lactotransferrin to an abnormally elevated rate. An excessive accumulation of lactotransferrin, as well as transported iron and aluminum, may lead to a cytotoxic effect resulting in the formation of intracellular lesions and neuronal death.
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Differential expression of advanced glycosylation end-products in neurons of different species.
The developmental time course and life span of the human brain are different from those of laboratory animals. These variations may be the reflection of metabolic differences of the neurons between different species. Using immunocytochemistry, we show that pyramidal neurons accumulate advanced glycosylation end products (AGEPs) formed by the Maillard reaction. However, the patterns of AGEPs accumulation in the pyramidal neuron were quite distinct between human and the 4 different animal species (horse, calf, pig, and rat) examined. In the human pyramidal neuron, AGEPs depict a granular, perikaryonal distribution, whereas in the animal brains, AGEPs show a nuclear staining pattern. The different patterns of AGEPs distribution in the pyramidal neurons suggest that AGEPs is an in vivo biochemical marker which distinguishes human pyramidal neurons from those of animals, and may help characterise pathologies specific to human.
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Ultrastructural localization of butyrylcholinesterase on neurofibrillary degeneration sites in the brains of aged and Alzheimer's disease patients.
Butyrylcholinesterase histochemical techniques were applied to vibratome sections of several cortical areas from the brains of non-demented aged and of Alzheimer's disease patients. At the light microscope level, all the senile plaque types and all the structures with neurofibrillary degeneration showed butyrylcholinesterase reaction product, whereas nearby neuronal perikarya and axons on the same slides remained unstained. Areas containing stained elements were selected, re-sectioned, and finally observed under the electron microscope. Focusing on the sites of neurofibrillary degeneration, butyrylcholinesterase reaction product was found in both intra- and extracellular neurofibrillary tangles, in neurites associated with plaques, and in neuropil threads that were either axons or dendrites. This reaction product was exclusively located over filament bundles, and sometimes covered them so completely that they could not be identified. When the filaments were only partially covered, it was possible to identify them as either paired helical filaments or straight filaments. Occasionally, neurofibrillary tangles, neuropil threads and plaque-associated neurites, all of them containing either paired helical filaments or straight filaments, were found to be completely free of butyrylcholinesterase reaction product. The origin and possible role of butyrylcholinesterase, which is ultrastructurally localized over elements presenting neurofibrillary degeneration, is discussed.
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Neuropathological changes in the cerebral cortex of 1258 cases from a geriatric hospital: retrospective clinicopathological evaluation of a 10-year autopsy population.
To examine the neuropathological and clinical characteristics of cerebral aging, we evaluated retrospectively a non-selected autopsy population of 1258 patients from the Geriatric Hospital of the University of Geneva School of Medicine. The prevalence of Alzheimer's disease increased with age below 90 years of age. In the nonagenarians and centenarians, there was a decline in the number of affected cases. The distribution with age of neurofibrillary tangles and senile plaques varied among the cortical areas studied. The CA1 field of the hippocampus and the inferior temporal cortex displayed increasing densities of neurofibrillary tangles with age, whereas the superior frontal and the occipital cortex were relatively spared, especially in patients in their tenth and eleventh decade. The percentage of cases presenting with senile plaques in the neocortex and hippocampal structure increased with age with a marked predominance of cases with moderate to high senile plaque densities. Neurofibrillary tangles were often observed in the CA1 field and the inferior temporal cortex of non-demented individuals and were present in most cases with Alzheimer's disease. Conversely, the involvement of the superior frontal and occipital cortex was moderate even in demented patients. The distribution of senile plaques was homogeneous in all of the neocortical areas independently of the clinical diagnosis. Moreover, there was no correlation between the presence of neurofibrillary tangles and senile plaques in the cerebral regions studied. These results indicate a differential topography of neurofibrillary tangles and senile plaques, and suggest that overt clinical signs of Alzheimer's disease are linked to the progression of the neurodegenerative process in neocortical areas.
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Pathological alterations of the cerebral microvasculature in Alzheimer's disease and related dementing disorders.
Alterations of the cerebral microvasculature have been reported in aging and in neurodegenerative disorders such as Alzheimer's disease. However, the exact role of microvascular alterations in the pathogenesis of neurodegeneration remains unknown. In the present report, the cerebral cortex microvasculature was studied by immunohistochemistry using a monoclonal antibody against vascular heparan sulfate proteoglycan protein core in normal aging controls. Alzheimer's disease, Down syndrome, Guam amyotrophic lateral sclerosis/parkinsonian dementia complex, Pick's disease and dementia pugilistica. In all dementing illnesses, increased microvascular pathology was evident compared to normal controls. Decreased microvascular density and numerous atrophic vessels were the primary abnormalities observed in all dementing disorders. These microvascular abnormalities demonstrated regional and laminar selectivity, and were primarily found in layers III and V of frontal and temporal cortex. Quantitative analysis employing computer-assisted microscopy demonstrated that the decrease in microvascular density in Alzheimer's disease was statistically significant compared to age-matched controls. In addition, extracellular heparan sulfate proteoglycan deposits were observed which colocalized with thioflavine S-positive senile plaques in Alzheimer's disease, Down syndrome and selected Guam dementia cases. In some cases, heparan sulfate proteoglycan was seen in senile plaques that appeared to be diffuse or primitive plaques that stained weakly with thioflavine. Heparan sulfate proteoglycan-containing neurons were also observed in Alzheimer's disease, as well as in Down syndrome and Guam cases. Glial staining for heparan sulfate proteoglycan was never observed. Our data support previous observations that microvascular pathology is found in aging and in Alzheimer's disease. The changes in Alzheimer's disease exceed those found in normal aging controls. We also found microvascular pathology in all other dementing disorders studied. Our studies further demonstrated that the microvascular pathology displays regional and laminar patterns which parallel patterns of neuronal loss. Finally, we also found that heparan sulfate proteoglycan is present in senile plaques and neurons not only as previously reported in Alzheimer's disease, but also in Down syndrome and Guam cases. Heparan sulfate proteoglycan in senile plaques may be derived from either the degenerating microvasculature or from degenerating neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
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Quantitative neuropathologic analysis of Pick's disease cases: cortical distribution of Pick bodies and coexistence with Alzheimer's disease.
Pick's disease is characterized morphologically by severe atrophy of the frontal and temporal lobes and the presence in the cerebral cortex of degenerative neuronal lesions referred to as Pick bodies. In the present study, we analyzed the regional and laminar distribution of Pick bodies in a series of 16 Pick's disease cases. These distribution and density patterns were compared with those observed for neurofibrillary tangles in Alzheimer's disease. Very high densities of Pick bodies were observed Ammon's horn, subiculum, entorhinal cortex, and in the granule cell layer of the dentate gyrus. In the frontal and temporal neocortex, they were preferentially distributed in layers II and VI. All of the Pick's disease cases also exhibited neurofibrillary tangles in the frontal and temporal areas and in the hippocampal formation, with higher densities in layers II-III than in layers V-VI of the neocortical regions. Interestingly, this laminar distribution of neurofibrillary tangles was strikingly different from that observed in Alzheimer's disease cases, where they were more numerous in the infragranular layers than in the supragranular layers. In addition, a few Pick's disease cases also had cortical senile plaques. These results suggest that the presence of neurofibrillary tangles in Pick's disease may be more frequent than previously reported, and that Pick's disease and Alzheimer's disease may coexist in certain cases. The lesion distribution patterns suggest that different populations of cortical neurons are affected in Pick's and Alzheimer's disease, and that alterations of select corticocortical and corticosubcortical projections may distinguish these forms of dementia. It is also possible that these two disorders share certain pathogenetic mechanisms, even though both display specific patterns of regional and neuronal vulnerability to the degenerative processes.
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Alzheimer's disease with asymmetric atrophy of the cerebral hemispheres: morphometric analysis of four cases.
To examine the clinicopathological correlations in rare Alzheimer's disease patients with asymmetric cerebral atrophy and to compare their pattern of cortical involvement by senile lesions with that observed in other cases with atypical Alzheimer's disease, we performed an extensive neuropathological analysis of the cerebral cortex in four such cases. Three patients presented with severe language impairment but relatively good preservation of praxis and gnosis even after several years of clinical evolution. Cerebral autopsies of these cases revealed a predominant left hemisphere atrophy. Conversely, in one case with marked right hemisphere atrophy, all of the cognitive functions were involved early in the course of dementia. Neurofibrillary tangles and senile plaques were preferentially localized in the prefrontal, temporal and posterior parietal cortex in both hemispheres, whereas the hippocampal formation displayed lower lesion densities than neocortical areas. Significantly higher neurofibrillary tangle and senile plaque densities were found in the more atrophic side in most of the areas studied. The ratio of neurofibrillary tangle and senile plaque densities between the two hemispheres was not correlated with the number of these lesions in the cerebral cortex. These results indicate that the degenerative process in demented cases with interhemispheric asymmetric cerebral atrophy is characterized by a widespread involvement of the neocortex by senile lesions and lacks clear regional topography of neurofibrillary tangle and senile plaque distribution. Moreover, the relative sparing of the hippocampus, comparable to that found in cases with focal progressive dementia, suggests that the dementing process may involve different cortical structures in cases with asymmetric cerebral atrophy than in typical Alzheimer's disease cases.
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Neurofibrillary tangle densities in the hippocampal formation in a non-demented population define subgroups of patients with differential early pathologic changes.
Detailed analyses of the neuropathologic changes in the cerebral cortex of elderly individuals and Alzheimer's disease patients have demonstrated that certain components of the neocortical and hippocampal circuits are likely to be selectively vulnerable. In order to investigate the distribution of lesions associated with aging as well as with the earliest symptoms of Alzheimer's disease, we performed a quantitative neuropathological evaluation of sixty-one non-demented patients from a geriatric hospital. All of the cases had neurofibrillary tangles in layer II of the entorhinal cortex, and many cases had an involvement of the CA1 field of the hippocampus and the inferior temporal cortex. In all of the cases, amyloid deposition was not correlated with age or with the number of neurofibrillary tangles. In addition, eight cases showed much higher neurofibrillary tangle counts than the remainder of the cases. It is proposed that these cases may represent the neuropathological correlate of the earliest stage of Alzheimer's disease that could antedate the appearance of clinical signs of cognitive decline and memory impairment.
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Calretinin-immunoreactive neocortical interneurons are unaffected in Alzheimer's disease.
Recent studies have revealed that select neuronal populations may display a differential sensitivity to degeneration in Alzheimer's disease. For example, large pyramidal neurons have been shown to be vulnerable, whereas small, local circuit neurons appear to be resistant to the pathologic process. More significantly, interneurons that contain the calcium-binding proteins parvalbumin and calbindin are particularly resistant to degeneration in Alzheimer's disease. Using a polyclonal antibody to the calcium-binding protein calretinin, we analyzed the possible changes in the subset of interneurons containing this protein in two neocortical areas that are generally devastated in Alzheimer's disease. In the prefrontal cortex as well as in the inferior temporal cortex, we observed no difference in the density of calretinin-immunoreactive neurons in Alzheimer's disease brains as compared to control cases. Moreover, the cellular morphology of these neurons was well preserved in the Alzheimer's disease cases. These data suggest that calretinin-immunoreactive neurons, like other calcium-binding protein-containing interneurons, are resistant to degeneration in Alzheimer's disease. The results support the notion that the pathological process in Alzheimer's disease involves specific cellular populations sharing particular morphological and neurochemical characteristics. In addition, it is possible that the presence of calcium-binding proteins confers a certain degree of resistance to degeneration in specific neuronal subsets.
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