Alzheimer's disease is the most common form of dementia in elderly individuals. Approximately 11% of the population older than 65, and up to 50% of individuals over 85 qualify as having "probable... more
Alzheimer's disease is the most common form of dementia in elderly individuals. Approximately 11% of the population older than 65, and up to 50% of individuals over 85 qualify as having "probable Alzheimer's disease" on the basis of clinical evaluation. Since the early description of the clinical symptoms and neuropathologic features of Alzheimer's disease, there has been an extraordinary growth in the knowledge of the morphologic and molecular characteristics of Alzheimer's disease. Although the pathogenetic events that lead to dementia are not yet fully understood, several hypotheses regarding the formation of the hallmark pathologic structures of Alzheimer's disease have been proposed. In this context, the use of specific histochemical techniques in the primate brain has greatly expanded our understanding of neuron typology, connectivity and circuit distribution in relation to neurochemical identity. In this respect, very specific subsets of cortical neurons and cortical afferents can be identified by their particular content of certain neurotransmitters and structural proteins. In this article, we discuss the possible relationships between the distribution of pathologic changes in aging, Alzheimer's disease, and possibly related dementing conditions, in the context of the specific elements of the cortical circuitry that are affected by these alterations. Also, evidence for links between the neurochemical phenotype of a given neuron and its relative vulnerability or resistance to the degenerative process are presented in order to correlate the distribution of cellular pathologic changes, neurochemical characteristics related to vulnerability, and affected cortical circuits.
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This article reviews the possible relationships between the localization of cellular pathologic changes in Alzheimer's disease (AD), and the distribution of neuronal components of the neocortical circuitry that are... more
This article reviews the possible relationships between the localization of cellular pathologic changes in Alzheimer's disease (AD), and the distribution of neuronal components of the neocortical circuitry that are affected by these alterations. In particular, evidence from the study of large autopsy series supporting the role of the inferior temporal cortex as a key area in the progression of the dementing process is presented. The notion of selective vulnerability in AD at the level of affected neocortical association areas, layers, and specific cell populations is discussed to provide insight into the molecular background of the development of neurofibrillary tangles within the cerebral cortex. Moreover, recent data on pathological correlates of apraxia in AD are examined in the light of the hypothesis of global corticocortical disconnection in this disorder.
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Research Interests: Cognitive Science, Neurogenesis, Biology, Immunohistochemistry, Apoptosis, and 15 moreNeural stem cell, Brain, Mutation, Mice, Animals, Embryonic Stem Cell, Astrocytes, Dentate Gyrus, Neuronal Differentiation, Embryonic Development, Embryos, Alzheimer Disease, Neurite Outgrowth, Cell count, and neuronal morphology
The term frontotemporal dementia has been used to classify several clinical syndromes previously described based on a relatively homogeneous symptomatology. Patients in this diagnostic group present with an insidious and gradual change in... more
The term frontotemporal dementia has been used to classify several clinical syndromes previously described based on a relatively homogeneous symptomatology. Patients in this diagnostic group present with an insidious and gradual change in personality and social conduct, early deficits of mental manipulation, sequencing and hierarchical organization processes, frontal-type amnesia, contrasting with preserved orientation, visuoconstructive and visuospatial abilities. Frontotemporal dementia may represent more than 20% of degenerative dementias and is currently considered as the third most common cause of dementia after Alzheimer's disease and Lewy body dementia. Biochemical and molecular genetic studies have made it possible to identify at least three biologically homogeneous subgroups of frontotemporal dementias: typical frontotemporal dementia cases with no tau or ubiquitin-positive neuronal and glial inclusions, two tauopathies, namely Pick's disease and frontotemporal dementia with parkinsonism linked to chromosome 17, and one ubiquitin-related disorder, the frontotemporal dementia with motor neuron disease. We provide here a detailed overview of current concepts regarding the clinical characteristics and etiopathogenesis of these conditions.
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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... more
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. Furthermore, the distribution of pathologic lesions in the AD cases with visual symptomatology revealed the disruption of specific visual association pathways, which are normally affected to a lesser degree in AD. These data suggest that in some cases of AD, the particular psychologic and neurologic symptomatology may be caused by the selective loss of specific corticocortical systems, as reflected by a differential distribution of the neuropathologic markers of the disease.
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The purpose of this study is to report a case of a very large arachnoid cyst in a patient having spent a very active life and who had never presented any neurological or psychiatric symptomatology beside a dementia in the last years of... more
The purpose of this study is to report a case of a very large arachnoid cyst in a patient having spent a very active life and who had never presented any neurological or psychiatric symptomatology beside a dementia in the last years of her life. The gross examination of the brain revealed the presence of a voluminous frontal bilateral cyst, located in the midline and displacing laterally the frontal lobes, so they displayed a foliated aspect. Microscopically, the examination of the cyst walls confirmed its arachnoid origin and the cerebral cortex contained lesions typical for senile dementia. This case exemplifies the histological nature and the pathogeny of arachnoid cysts, in particular of congenital origin. This also shows that the very early occurrence of such a malformation does not prevent the development of functional neuronal pathways, owing to the important plasticity of the central nervous system.
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Recent accumulated evidence indicates that episodic memory impairments could be part of the initial clinical expression of frontotemporal dementia (FTD). An early study on this issue was carried out by Constantinidis and colleagues in... more
Recent accumulated evidence indicates that episodic memory impairments could be part of the initial clinical expression of frontotemporal dementia (FTD). An early study on this issue was carried out by Constantinidis and colleagues in 1974, but it was subsequently overlooked for a long period of time. The scope of the present research was: (a) to explore the presence of early episodic memory impairments in the entire population of neuropathologically confirmed FTD patients from the Geneva brain collection; and (b) to expand the present insight on the association between the initial symptomatology and various characteristics, namely gender, age at onset, disease duration, and presence of Pick body neuropathology. A careful review of the records of 50 FTD patients hospitalized at the Department of Psychiatry of the Bel-Air Hospital, Geneva, Switzerland, from 1929 to 1999, was conducted. Further in-depth neuropathological analysis with novel immunohistological methods was carried out i...
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ABSTRACT
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Braak's neurofibrillary tangle (NFT) pathology staging system of Alzheimer disease (AD) correlates generally with clinical data. Recently, Braak's group proposed an Aß-protein staging based on the progression of amyloid deposition... more
Braak's neurofibrillary tangle (NFT) pathology staging system of Alzheimer disease (AD) correlates generally with clinical data. Recently, Braak's group proposed an Aß-protein staging based on the progression of amyloid deposition in the medial temporal lobe. To examine its clinical validity and evaluate whether it adds predictive power to NFT-based staging, we performed a study comparing both neuropathological classifications with clinical dementia rating scale (CDR) scores in a large autopsy series. The 2 neuropathological staging systems were strongly correlated. Their association with clinical severity was highly significant. However, the strength of the relationship was greater for NFT-based staging. It accounted for 26.5% of the variability in clinical severity, Aß-protein-based staging for 13.0%, and age for 4.4%. Compared to NFT-based staging, the Aß-protein-based system was less able to distinguish mild cognitive changes from dementia and showed marked overlap among...
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In the present study, we analyzed the distribution of lactoferrin by immunohistochemistry in the cerebral cortex of patients presenting with Alzheimer’s disease (AD), Down’s syndrome, amyotrophic lateral sclerosis/parkinsonism-dementia... more
In the present study, we analyzed the distribution of lactoferrin by immunohistochemistry in the cerebral cortex of patients presenting with Alzheimer’s disease (AD), Down’s syndrome, amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam (ALS/PDC), sporadic ALS, or Pick’s disease. The results show that lactoferrin accumulates in the typical lesions of each pathologic condition investigated. For instance, in AD and Guamanian cases, a subpopulation of neurofibrillary tangles was intensely labeled in the hippocampal formation (up to 100 and 180/mm2, respectively) and inferior temporal cortex (up to 20 and 120/mm2, respectively). 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 to amyloid sA4 protein, although fewer neurofibrillary tangles were positive for lactoferrin than for tau protein in neocortical areas. Neuronal cytoplasmic staining 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’s syndrome. Lactoferrin was also strongly associated with Betz cells and motoneurons in the primary motor cortex, and these same lactoferrin-immunoreactive motoneurons were severely affected in the cases with ALS. The upregulation and the cellular distribution of lactoferrin observed in these neurodegenerative disorders may be key factors in the mechanisms of iron and aluminum transport and delivery into neurons potentially more vulnerable to the degenerative process. Through this specific mechanism, iron and aluminum may accumulate within select neuron populations and exert cytotoxic effects, which may result in the formation of intracellular lesions and neuronal death.
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Betz cells are giant motoneurons located in layer Vb of the primate primary motor cortex. We conducted stereological analyses of Betz cells and neighboring pyramidal cells from the brains of six neurologically normal elderly humans to... more
Betz cells are giant motoneurons located in layer Vb of the primate primary motor cortex. We conducted stereological analyses of Betz cells and neighboring pyramidal cells from the brains of six neurologically normal elderly humans to determine their volume, total number, and spatial distribution, and to relate these data to functional localization. The distribution of cellular volumes exhibits a bimodal pattern, delineating two different subpopulations. Betz cell volumes follow a mediolateral gradient, the largest Betz cells being located on the most medial part of the motor cortex. Additionally, the shape of Betz cells varies between the rostral and caudal parts of the primary motor cortex, supporting the notion that there are anatomically distinct zones in primary motor cortex. The total number of Betz cells per hemisphere accounts for about one-tenth of the total number of pyramidal cells in layer Vb. Analysis of spatial distribution using Voronoi tessellation revealed maximal c...
Research Interests: Dementia, Progressive Supranuclear Palsy, Amyotrophic Lateral Sclerosis, Biological Sciences, Humans, and 15 moreFemale, Functional Imaging, Male, Motor Cortex, Neurons, Spatial Distribution, Aged, Neurodegenerative Disease, Cytoarchitecture, Primary Motor Cortex, Cell Volume, Cell Size, pyramidal cells, parkinsonian disorders, and Medical and Health Sciences
Alzheimer disease is characterized by cognitive decline, senile plaques of β-amyloid (Aβ) peptides, neurofibrillary tangles composed of hyperphosphorylated τ proteins and neuronal loss. Aβ and τ are useful markers in the cerebrospinal... more
Alzheimer disease is characterized by cognitive decline, senile plaques of β-amyloid (Aβ) peptides, neurofibrillary tangles composed of hyperphosphorylated τ proteins and neuronal loss. Aβ and τ are useful markers in the cerebrospinal fluid (CSF). C-Jun N-terminal kinases (JNKs) are serine-threonine protein kinases activated by phosphorylation and involved in neuronal death. In this study, Western blots, enzyme-linked immunosorbent assay and histological approaches were used to assess the concentrations of Aβ, τ and JNK isoforms in postmortem brain tissue samples (10 Alzheimer disease and 10 control) and in CSF samples from 30 living patients with Alzheimer disease and 27 controls with neurologic disease excluding Alzheimer disease. Patients with Alzheimer disease were followed for 1-3 years and assessed using Mini-Mental State Examination scores. The biochemical and morphological results showed a significant increase of JNK3 and phosphorylated JNK levels in patients with Alzheimer ...
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ABSTRACT In cognitively intact individuals and patients with Alzheimer’s disease (AD) the formation of neurofibrillary tangles (NFTs), senile plaques (SPs), and the synaptic loss characterizes the neuropathology of brain aging. There is a... more
ABSTRACT In cognitively intact individuals and patients with Alzheimer’s disease (AD) the formation of neurofibrillary tangles (NFTs), senile plaques (SPs), and the synaptic loss characterizes the neuropathology of brain aging. There is a differential cortical vulnerability to the degenerative process in extreme brain aging. In the oldest-old population the distribution and the severity of NFTs and SPs could be different compared to younger persons.
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About one third of Alzheimer's disease (AD) patients develop some parkinsonian features, yet half of them do not have Lewy body pathology at autopsy. The neuropathological substrate of parkinsonism in AD is still unclear. In the... more
About one third of Alzheimer's disease (AD) patients develop some parkinsonian features, yet half of them do not have Lewy body pathology at autopsy. The neuropathological substrate of parkinsonism in AD is still unclear. In the present study, we measured neuronal and neurofibrillary tangles (NFTs) densities in the substantia nigra pars compacta (SN) and in the putamen of 22 AD patients, 11 with and 11 without parkinsonism, here defined as the presence of bradykinesia and at least one of resting tremor, rigidity, or gait disorders. Our study showed that parkinsonism associated with AD was related to a significant loss of neurons both in the SN and in the putamen, suggesting pre-and postsynaptic alterations of the nigrostriatal pathway. Neuronal tau deposition was a less important factor as density of NFTs correlated with parkinsonism only in the SN but not in the putamen. We propose that a subgroup of pure AD patients develop parkinsonian symptoms as a result of neuronal loss in...
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The occurrence of microvascular and small macrovascular lesions and Alzheimer's disease (AD)-related pathology in the aging human brain is a well-described phenomenon. Although there is a wide consensus about the relationship between... more
The occurrence of microvascular and small macrovascular lesions and Alzheimer's disease (AD)-related pathology in the aging human brain is a well-described phenomenon. Although there is a wide consensus about the relationship between macroscopic vascular lesions and incident dementia, the cognitive consequences of the progressive accumulation of these small vascular lesions in the human brain are still a matter of debate. Among the vast group of small vessel-related forms of ischemic brain injuries, the present review discusses the cognitive impact of cortical microinfarcts, subcortical gray matter and deep white matter lacunes, periventricular and diffuse white matter demyelinations, and focal or diffuse gliosis in old age. A special focus will be on the sub-types of microvascular lesions not detected by currently available neuroimaging studies in routine clinical settings. After providing a critical overview of in vivo data on white matter demyelinations and lacunes, we summar...
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Neuronal death is a pathological hallmark of Alzheimer's disease. We have shown previously that phosphorylated double-stranded RNA-dependent protein kinase is present in degenerating hippocampal neurons and in senile plaques of... more
Neuronal death is a pathological hallmark of Alzheimer's disease. We have shown previously that phosphorylated double-stranded RNA-dependent protein kinase is present in degenerating hippocampal neurons and in senile plaques of Alzheimer's disease brains and that genetically down-regulating double-stranded RNA-dependent protein kinase activity protects against in vitro beta-amyloid peptide neurotoxicity. In this report, we showed that two double-stranded RNA-dependent protein kinase blockers attenuate, in human neuroblastoma cells, beta-amyloid peptide toxicity evaluated by caspase 3 assessment. In addition, we have used the newly engineered APP(SL)/presenilin 1 knock-in transgenic mice, which display a severe neuronal loss in hippocampal regions, to analyze the activation of double-stranded RNA-dependent protein kinase. Western blots revealed the increased levels of activated double-stranded RNA-dependent protein kinase and the inhibition of eukaryotic initiation factor 2 a...
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Previous studies reported an association between cortical Lewy body (LB) formation and dementia in Parkinson's disease (PD). However, it is unclear whether cognitive decline in this disorder is related to specific patterns of LB... more
Previous studies reported an association between cortical Lewy body (LB) formation and dementia in Parkinson's disease (PD). However, it is unclear whether cognitive decline in this disorder is related to specific patterns of LB distribution within the cerebral cortex. Moreover, the prediction of cognitive status based on concomitant assessment of LB and Alzheimer's disease lesions has led to conflicting results. We performed a clinicopathological study in 22 elderly PD patients in whom parkinsonism preceded cognitive decline by at least 3 years. Cognitive status was assessed prospectively using the clinical dementia rating scale (CDR); quantitative assessment of LB, neurofibrillary tangles (NFT), and senile plaques (SP) was performed in Brodmann areas 9, 21, 24, 40 and the entorhinal cortex. Statistical analysis was performed using both correlation coefficients and logistic regression models. There was a highly significant correlation between CDR scores and regional LB scor...
Research Interests: Cognition, Immunohistochemistry, Medicine, Humans, Cerebral Cortex, and 15 moreFemale, Male, Clinical Sciences, Aged, Middle Aged, Entorhinal Cortex, ACTA, Disease Progression, Correlation coefficient, Cognitive Decline, Logistic Regression Model, Cognition disorders, Anterior cingulate cortex, Cell count, and Lewy bodies
The influence of human immunoglobulins (Ig) in neuronal cytoskeleton stability was studied in vitro. Here we show that human Ig and Fc fragments stimulate animal and human microtubule assembly by binding to microtubules via tau isoforms.... more
The influence of human immunoglobulins (Ig) in neuronal cytoskeleton stability was studied in vitro. Here we show that human Ig and Fc fragments stimulate animal and human microtubule assembly by binding to microtubules via tau isoforms. In presence of Ig, microtubules show increased aggregation, twisting and rigidity. Non-immune Ig and Fc fragments promote microtubule assembly in temperature-dependent manner and stabilize microtubules at a molecular ratio of 1 Ig per 4 tubulin dimers. These in vitro data provide an experimental support for an immuno-mediated modulation of the cytoskeleton. In conjunction with previous neuropathological data, they suggest that Ig could participate in early stages of neurodegeneration by affecting the microtubule stability in vivo.
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Cornelia de Lange syndrome (CDLS) is a rare multisystemic malformative syndrome of uncertain etiology characterized by severe psychomotor and mental retardation. Here we report the neuropathological analysis of a 35-year-old patient who... more
Cornelia de Lange syndrome (CDLS) is a rare multisystemic malformative syndrome of uncertain etiology characterized by severe psychomotor and mental retardation. Here we report the neuropathological analysis of a 35-year-old patient who displayed the classical clinical symptomatology of CDLS. A congenital dysgenesis of the brain was evident including abnormal convolution patterns of the cerebral gyri, frontal lobe hypoplasia and focal lack of myelination in layers V and VI of the left temporal cortex. In addition, there were vascular scars in the CA2-3 region of the left hippocampus and in the right parietal cortex as well as a few neurofibrillary tangles in the CA fields of the hippocampus and in the entorhinal cortex. In contrast to previous reports, there were no midline cerebral dysgenesis and no ectopic neuron formations in the present case. Neuronal loss and gliosis were also absent in all cortical and subcortical areas. Our observations suggest that the main neurodevelopmenta...
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The morphological characteristics and distribution patterns of neurons immunoreactive for antisera against six biologically active peptides were examined by indirect immunofluorescence in the human brain. The peptides studied were:... more
The morphological characteristics and distribution patterns of neurons immunoreactive for antisera against six biologically active peptides were examined by indirect immunofluorescence in the human brain. The peptides studied were: met-enkephalin, leu-enkephalin, substance P, somatostatin, cholecystokinin and vasoactive intestinal peptide. The tissue samples for this study were removed, dissected and placed into fixative within 4 h post-mortem. Regional differences throughout the entire neuraxis were observed in the localization of cell bodies, fibers and terminals for the various peptides. The observations reported in this article demonstrate certain distribution patterns for peptide immunoreactivities that appear to be specific to the human brain when compared to other species. These morphologic studies establish a valuable framework for the further analysis of the role of peptide-containing neuronal circuits in normal and diseased human brain.
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Neuropathological hallmarks of... more
Neuropathological hallmarks of Alzheimer's disease (AD) include tangles (NFT) and beta amyloid (Aβ) plaques. Despite numerous neuropathological studies that assessed the relationship of cognitive decline with neuropathologic lesions, their correlation still remains unclear. NFTs and Aβ plaques have been widely implicated and described in normal aging. The number of NFTs in the CA1 and the entorhinal cortex seems to be more closely related to cognitive status, compared to the amyloid load whose role still remains controversial in the AD. In this review, we refer to our main studies performed in Geneva during the past two decades attempting to assess the correlation of pathology with clinical expression. The theory of cognitive reserve has been proposed for further understanding of interindividual differences in terms of compensation despite the presence of pathological lesions. The increasing prevalence of the AD, the limitations of actual treatments, as well as the high public cost reflect the imperative need for better therapeutic and early diagnosis strategies in the future.
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The progressive development of Alzheimer's disease (AD)-related lesions such as neurofibrillary tangles,amyloid... more
The progressive development of Alzheimer's disease (AD)-related lesions such as neurofibrillary tangles,amyloid deposits and synaptic loss within the cerebral cortex is a main event of brain aging.Recent neuropathologic studies strongly suggested that the clinical diagnosis of dementia depends more on the severity and topography of pathologic changes than on the presence of a qualitative marker. However, several methodological problems such as selection biases, case-control design,density-based measures, and masking effects of concomitant pathologies should be taken into account when interpreting these data. In last years, the use of stereologic counting permitted to define reliably the cognitive impact of AD lesions in the human brain. Unlike fibrillar amyloid deposits that are poorly or not related to the dementia severity, the use of this method documented that total neurofibrillary tangles and neuron numbers in the CA1 field are the best correlates of cognitive deterioration in brain aging. Loss of dendritic spines in neocortical but not hippocampal areas has a modest but independent contribution to dementia. In contrast, the importance of early dendritic and axonal tau-related pathologic changes such as neuropil threads remains doubtful. Despite these progresses, neuronal pathology and synaptic loss in cases with pure AD pathology cannot explain more than 50% of clinical severity. The present review discusses the complex structure/function relationships in brain aging and AD within the theoretical framework of the functional neuropathology of brain aging.
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Direct force measurements of lift and drag for a three-dimensional wing with a lambda-shaped planform are made in the Fejer Wind Tunnel at IIT using high angles of attack with and without various unsteady forcing conditions through a... more
Direct force measurements of lift and drag for a three-dimensional wing with a lambda-shaped planform are made in the Fejer Wind Tunnel at IIT using high angles of attack with and without various unsteady forcing conditions through a leading-edge slot. In addition to changing the pulsation frequency in the range of 2--200 Hz, the waveform was varied between sinusoidal, triangular
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Lipofuscin pigment accumulation is among the most prominent markers of cellular aging in postmitotic cells. The formation of lipofuscin is related to oxidative enzymatic activity and free radical-induced lipid peroxidation. In various... more
Lipofuscin pigment accumulation is among the most prominent markers of cellular aging in postmitotic cells. The formation of lipofuscin is related to oxidative enzymatic activity and free radical-induced lipid peroxidation. In various mammals such as rat, dog, macaque as well as in cheirogaleid primates, most of the large neurons, such as cerebellar Purkinje cells and neocortical pyramidal cells, show heavy lipofuscin accumulation in adulthood. In contrast, a well-known yet poorly studied feature of the aging human brain is that although lipofuscin accumulation is most marked in large neurons of the cerebral cortex, the large neurons of the cerebellar cortex-the Purkinje cells-appear to remain free of lipofuscin accumulation. It is however, not known whether this characteristic of human Purkinje cells is shared with other primates or other mammals. This study reports results from histological observation of Purkinje cells in humans, non-human primates, and other mammals. Procedures include histochemistry, immunocytochemistry, and fluorescence microscopy. Abundant lipofuscin deposition was observed in Purkinje cells of all the species we examined except Homo sapiens (including Alzheimer's disease cases) and Pan troglodytes. In contrast, lipofuscin deposition was observed in neurons of the dentate nucleus. Our findings suggest that when compared with other primates, Purkinje cells in chimpanzees and humans might share a common aging pattern that involves mechanisms for neuroprotection. This observation is important when considering animal models of aging.
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Research Interests: Bipolar Disorder, Evidence Based Medicine, Neuropsychopharmacology, Risk assessment, Medicine, and 11 moreNeuroprotection, Humans, Animals, Neuro, Neurons, Systematic review, Reproducibility of Results, Risk Assessment, Neuroprotective Agents, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Aging, Brain, Prospective studies, Humans, Cerebral Cortex, and 15 moreFemale, Male, Regression Analysis, Brain Ischemia, Clinical Sciences, Aged, Middle Aged, Disease Progression, Neurosciences, Logistic Models, Predictive value of tests, Cognition disorders, Cerebral Infarction, Demyelinating diseases, and Cardiovascular medicine and haematology
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About 30 % of Alzheimer’s disease (AD) patients develop parkinsonian features, but Lewy body pathology is not always present at autopsy. So the neuropathological substrate of extrapyramidal signs in AD remains unclear. In the present... more
About 30 % of Alzheimer’s disease (AD) patients develop parkinsonian features, but Lewy body pathology is not always present at autopsy. So the neuropathological substrate of extrapyramidal signs in AD remains unclear. In the present study neuronal and neurofibrillary tangle (NFT) densities were counted in the substantia nigra pars compacta (SN) and in the putamen of 22 AD patients, 11 with and 11 without parkinsonism. Parkinsonism was defined as the presence of bradykinesia and at least one of resting tremor, rigidity, or gait disorders. Our results showed that parkinsonism in AD is related to a significant neuronal loss both in the SN and in the putamen, suggesting pre- and postsynaptic alterations of the nigrostriatal pathway.
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Alzheimer’s disease (AD) is characterized neuropathologically by the presence of two classical histologic hallmarks, neurofibrillary tangles (NFT) and senile plaques (SP). Recent analyses of the distribution of the pathologic changes in... more
Alzheimer’s disease (AD) is characterized neuropathologically by the presence of two classical histologic hallmarks, neurofibrillary tangles (NFT) and senile plaques (SP). Recent analyses of the distribution of the pathologic changes in AD suggest that this disease affects select populations of neurons within the cerebral cortex that are characterized by specific regional and laminar distribution and connectivity patterns, whereas other neuronal subgroups are remarkably resistant to the degenerative process. Based on the distribution of NFT and SP, it has been proposed that a global corticocortical disconnection leads to the loss of integrated functions exhibited by AD patients. Furthermore, it appears that lesion distribution follows certain organization schemes and that these regional and laminar patterns may relate cortical circuits to clinical symptoms. Several neuropathologic studies have documented the presence of NFT and SP in the cerebral cortex of non-demented elderly individuals (Mountjoy et al., 1983; Tomlinson et al., 1968). More recently, it has been shown that amyloid deposition and NFT formation are not only common features of brain aging, but that they are present within certain regions of the cerebral cortex with densities comparable to those observed in demented patients (Bouras et al., 1993; Hof et al., 1992). Thus, high NFT densities have been demonstrated in the hippocampal formation and temporal neocortex, but sparse NFT in the other neocortical regions in cases presenting with very mild signs of cognitive decline (Bouras et al., 1993; Hof et al., 1992).
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Non-insulin-dependent diabetes mellitus (NIDDM) and dementia are both characterized by high prevalence in later life (Muller, 1993). Differences in prevalence of NIDDM according to regions and races are well-known. In an industrialized... more
Non-insulin-dependent diabetes mellitus (NIDDM) and dementia are both characterized by high prevalence in later life (Muller, 1993). Differences in prevalence of NIDDM according to regions and races are well-known. In an industrialized society, with a predominantly white population, the rate of NIDDM increases linearly starting from 35 years old, reaching 15% at the age of 75 (Wilson et al., 1986) and 20% at the age of 80 (Morley and Perry, 1991). As for Alzheimer’s Disease (AD), it follows an exponential curve starting from the age of 50, reaching 30% for the 85 year-old population (Skoog et al., 1993).