Les cellules de Betz du cortex moteur primaire : analyse stéréologique et fonctionnelle

Les cellules de Betz sont des motoneurones géants situés dans la cinquième couche du cortex moteur primaire des primates. Une analyse stéréologique des cellules de Betz et des neurones pyramidaux adjacents a permis d'établir leur volume, leur nombre total et leur distribution spatiale tout en corrélant ces résultats à une cartographie fonctionnelle du cortex cérébral. Les données obtenues montrent que les cellules de Betz suivent un gradient médio-latéral le long du gyrus précentral, leur forme et leur densité variant selon leur localisation. Ces résultats suggèrent que les cellules de Betz possèdent une distribution subrégionale particulière qui pourrait correspondre à certains aspects de la parcellisation fonctionnelle de l'aire 4.Cette étude établit un lien entre l'histologie et l'imagerie fonctionnelle, le vieillissement du cerveau, les pathologies neurodégénératives telles que la sclérose latérale amyotrophique et à complexes dégénératifs de Guam et la spécialisation du cortex à travers l'évolution des espèces de primates

Stereologic analysis of hippocampal Alzheimer's disease pathology in the oldest-old: evidence for sparing of the entorhinal cortex and CA1 field

Several neuropathologic analyses postulate that Alzheimer disease (AD) in the oldest-old is associated with substantial neurofibrillary tangle (NFT) formation in the CA fields of the hippocampus and neuronal loss confined to the entorhinal cortex. All of these studies have measured densities, rather than absolute numbers, and most do not take into account the potential interaction between the above pathological hallmarks in a global multivariate analysis. We present here a stereologic analysis of AD-related pathology in 12 oldest-old individuals including a complete assessment of total NFT, neuron numbers and amyloid volume in entorhinal cortex, CA fields, and dentate gyrus. The progression of NFT numbers and amyloid volume across the different Clinical Dementia Rating (CDR) groups was significantly slower in these cases compared to previously reported younger cases. Although patients with mild and moderate dementia showed significantly lower mean neuron numbers compared to CDR 0-0.5 cases, there was a marked overlap in individual values among CDR groups. A modest proportion of the variability in CDR scores was explained by NFT numbers in the CA2 field (18.1%) and the dentate gyrus (17.3%). In contrast, neither Nissl-stained neuron numbers nor total amyloid volume in the areas studied significantly predicted cognitive status. These data indicate that the occurrence and progression of AD-related pathologic changes are not an unavoidable consequence of aging. They also suggest that dementia in extreme aging depends more on the damage of hippocampal subdivisions commonly less affected than on severe NFT formation and neuronal loss in the CA1 field and entorhinal corte

Cognitive impact of neuronal pathology in the entorhinal cortex and CA1 field in Alzheimer's disease

The relative contribution of Alzheimer's disease (AD) hippocampal neuronal pathology in cognitive decline is still a matter of debate. To address this issue, we performed a stereological analysis of layer II of the entorhinal cortex and the CA1 field of the hippocampus in 34 autopsy cases covering the whole spectrum of old age and Clinical Dementia Rating (CDR) scores. In both areas, the proportion of neurofibrillary tangle (NFT)-containing neurons increased steadily as a function of the CDR score. Questionable dementia was associated with a 1.9% neuronal loss in the entorhinal cortex and 26% in the CA1 field. NFT numbers predicted only 38% of the neuron number variability in the entorhinal cortex and 55% in the CA1 field. Neuron counts in the entorhinal cortex and both neuron and NFT counts in the CA1 field were significantly associated with cognitive status explaining 25% and 44% of the CDR variability, respectively. Our data reveal a dissociation between the patterns of progression of NFT and neuronal loss in the entorhinal cortex and CA1 field. Moreover, they show that less than 50% of the cognitive variability may be attributable to AD neuronal pathology in these area

Cognitive impact of Alzheimer disease neuronal pathology: lessons from centenarians

The relative contribution of Alzheimer disease (AD) hippocampal neuronal pathology in cognitive decline is still matter of debate. To address this issue, we performed a stereologic analysis of layer II of the entorhinal cortex and the CA1 field of the hippocampus in 34 autopsy cases covering the whole spectrum of old age (with 30% of nonagenarians and centenarians) and Clinical Dementia Rating (CDR) scale scores. In both areas, the proportion of NFT-containing neurons increased steadily as a function of the CDR score. Questionable dementia was associated with a 1.9% neuronal loss in the entorhinal cortex and 26% in the CA1 field. NFT numbers predicted only 38% of the neuron number variability in the entorhinal cortex and 55% in the CA1 field. Neuron counts in the entorhinal cortex and both neuron and NFT counts in the CA1 field were significantly associated with cognitive status explaining 25% and 44% of the CDR variability, respectively. Our data reveal a dissociation between the patterns of progression of NFT and neuronal loss in the entorhinal cortex and CA1 field. Moreover, they show that less than 50% of the cognitive variability may be attributable to AD neuronal pathology in these areas

Stereologic analysis of microvascular morphology in the elderly: Alzheimer disease pathology and cognitive status

The presence of microvascular changes has been documented both in brain aging and Alzheimer disease (AD), although the relationship between the morphometry of brain capillaries and cognitive impairment is still unknown. We performed an analysis of capillary morphometric parameters and AD-related pathology in 19 elderly individuals with variable degrees of cognitive decline. Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale. Total capillary lengths and numbers as well as mean length-weighted diameter, total neurofibrillary tangle (NFT) and neuron numbers, and amyloid volume were estimated in entorhinal cortex and the CA1 field. Total capillary numbers and mean diameters explained almost 40% of the neuron number variability in both the CA1 and entorhinal cortex. Total capillary length and numbers in the CA1 and entorhinal cortex did not predict cognitive status. Mean capillary diameters in the CA1 and entorhinal cortex were significantly related to CDR scores, explaining 18.5% and 31.1% of the cognitive variability, respectively. This relationship persisted after controlling for NFT and neuron numbers in multivariate regression models. Consistent with the growing interest about microvascular pathology in brain aging, the present data indicate that changes in capillary morphometric parameters may represent independent predictors of AD-related neuronal depletion and cognitive decline

Stereologic analysis of microvascular morphology in the elderly: Alzheimer disease pathology and cognitive status

The presence of microvascular changes has been documented both in brain aging and Alzheimer disease (AD), although the relationship between the morphometry of brain capillaries and cognitive impairment is still unknown. We performed an analysis of capillary morphometric parameters and AD-related pathology in 19 elderly individuals with variable degrees of cognitive decline. Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale. Total capillary lengths and numbers as well as mean length-weighted diameter, total neurofibrillary tangle (NFT) and neuron numbers, and amyloid volume were estimated in entorhinal cortex and the CA1 field. Total capillary numbers and mean diameters explained almost 40% of the neuron number variability in both the CA1 and entorhinal cortex. Total capillary length and numbers in the CA1 and entorhinal cortex did not predict cognitive status. Mean capillary diameters in the CA1 and entorhinal cortex were significantly related to CDR scores, explaining 18.5% and 31.1% of the cognitive variability, respectively. This relationship persisted after controlling for NFT and neuron numbers in multivariate regression models. Consistent with the growing interest about microvascular pathology in brain aging, the present data indicate that changes in capillary morphometric parameters may represent independent predictors of AD-related neuronal depletion and cognitive declin

Morphological substrates of cognitive decline in nonagenarians and centenarians: A new paradigm?

Brain aging is characterized by the formation of neurofibrillary tangles (NFT) and senile plaques (SP) in both cognitively intact individuals and patients with Alzheimer's disease (AD). The ubiquitous presence of these lesions and the steady increase of the prevalence of dementia up to 85 years have strongly supported a continuum between normal brain aging and AD. In this context, the study of nonagenarians and centenarians could provide key informations about the characteristics of extreme aging. We provide here a detailed review of currently available neuropathological data in very old individuals and critically discuss the patterns of NFT, SP and neuronal loss distribution as a function of age. In younger cohorts, NFTs are usually restricted to hippocampal formation, whereas clinical signs of dementia appear when temporal neocortex is involved. SPs would not be a specific marker of cognitive impairment as no correlation was found between their quantitative distribution and AD severity. The low rate of AD lesions even in severe AD as well as the weakness of clinicopathological correlations reported in the oldest-old indicate that AD pathology is not a mandatory phenomenon of increasing chronological age. Our recent stereological observations of hippocampal microvasculature in oldest-old cases challenge the traditional lesional model by revealing that mean capillary diameters is an important structural determinant of cognition in this age group

Morphological substrates of cognitive decline in nonagenarians and centenarians: a new paradigm ?

Brain aging is characterized by the formation of neurofibrillary tangles (NFT) and senile plaques (SP) in both cognitively intact individuals and patients with Alzheimer's disease (AD). The ubiquitous presence of these lesions and the steady increase of the prevalence of dementia up to 85 years have strongly supported a continuum between normal brain aging and AD. In this context, the study of nonagenarians and centenarians could provide key informations about the characteristics of extreme aging. We provide here a detailed review of currently available neuropathological data in very old individuals and critically discuss the patterns of NFT, SP and neuronal loss distribution as a function of age. In younger cohorts, NFTs are usually restricted to hippocampal formation, whereas clinical signs of dementia appear when temporal neocortex is involved. SPs would not be a specific marker of cognitive impairment as no correlation was found between their quantitative distribution and AD severity. The low rate of AD lesions even in severe AD as well as the weakness of clinicopathological correlations reported in the oldest-old indicate that AD pathology is not a mandatory phenomenon of increasing chronological age. Our recent stereological observations of hippocampal microvasculature in oldest-old cases challenge the traditional lesional model by revealing that mean capillary diameters is an important structural determinant of cognition in this age group