Laminar distribution of neurofilament inclusions and swollen achromatic neurons in neurofilament inclusion disease (NID)

The laminar distribution of the neurofilament inclusions (NI) and swollen achromatic neurons (SN) was studied in gyri of the temporal cortex in four patients with neurofilament inclusion disease (NID). In 84% of gyri analysed, the density of the NI was maximal in the lower cortical laminae. The distribution of the SN was more variable than the NI. Density was maximal in the lower cortex in 46% of gyri, in the upper cortical laminae in 8% of gyri, and a bimodal distribution in 15% of gyri. In the remaining gyri, there was a more even distribution of SN with cortical depth. In 31% of gyri, the vertical density of the NI was positively correlated with that of the SN. The data suggest that cortical degeneration in the temporal lobe of NID initially affects neurons in the lower laminae. Subsequently, the pathology may spread to affect much of the cortical profile, the SN preceding the appearance of the NI.

Laminar distribution of the pathological changes in frontal and temporal cortex in 8 patients with progressive supranuclear palsy

OBJECTIVE: To determine the laminar distribution of the pathological changes in the cerebral cortex in progressive supranuclear palsy (PSP). METHOD: The distribution of the abnormally enlarged neurons (EN), surviving neurons, neurofibrillary tangles (NFT), glial inclusions (GI), tufted astrocytes (TA), and neuritic plaques (NP) were studied across the cortex in tau immunolabeled sections of frontal and temporal cortex in 8 cases of PSP. RESULTS: The distribution of the NFT was highly variable with no consistent pattern of laminar distribution. The GI were distributed either in the lower laminae or uniformly across the cortex. Surviving neurons exhibited either a density peak in the upper laminae or a bimodal distribution was present with density peaks in the upper and lower laminae. The EN and glial cell nuclei were distributed primarily in the lower cortical laminae. There were positive correlations between the densities of the EN and glial cell nuclei and negative correlations between the surviving neurons and glial cells. No correlations were present between the densities of the NFT and GI. CONCLUSION: Cortical pathology in PSP predominantly affects the lower laminae but may spread to affect the upper laminae in some cases. The NFT and GI may have different laminar distributions and gliosis occurs concurrently with neuronal enlargement.

Laminar distribution of β-amyloid deposits in dementia with Lewy bodies and in Alzheimer's disease

This study tested whether the laminar distribution of the β-amyloid (Aβ) deposits in dementia with Lewy bodies (DLB) cases with significant Alzheimer's disease (AD) pathology (DLB/AD) was similar to "pure" AD. In DLB/AD, the maximum density of the diffuse and primitive deposits occurred either in the upper laminae or a bimodal distribution was present with density peaks in the upper and lower laminae. A bimodal distribution of the classic Aβ deposits was also observed. Compared with AD, DLB/AD cases had fewer primitive deposits relative to the diffuse and classic deposits; the primitive deposits exhibited a bimodal distribution more frequently, and the diffuse deposits occurred more often in the upper laminae. These results suggest that Aβ pathology in DLB/AD may not simply represent the presence of associated AD. © 2006 Sage Publications.

Multiple system atrophy: laminar distribution of the pathological changes in frontal and temporal neocortex--a study in ten patients

OBJECTIVE: To determine the distribution of the pathological changes in the neocortex in multiple-system atrophy (MSA). METHOD: The vertical distribution of the abnormal neurons (neurons with enlarged or atrophic perikarya), surviving neurons, glial cytoplasmic inclusions (GCI) and neuronal cytoplasmic inclusions (NI) were studied in alpha-synuclein-stained material of frontal and temporal cortex in ten cases of MSA. RESULTS: Abnormal neurons exhibited two common patterns of distribution, viz., density was either maximal in the upper cortex or a bimodal distribution was present with a density peak in the upper and lower cortex. The NI were either located in the lower cortex or were more uniformly distributed down the cortical profile. The distribution of the GCI varied considerably between gyri and cases. The density of the glial cell nuclei was maximal in the lower cortex in the majority of gyri. In a number of gyri, there was a positive correlation between the vertical densities of the abnormal neurons, the total number of surviving neurons, and the glial cell nuclei. The vertical densities of the GCI were not correlated with those of the surviving neurons or glial cells but the GCI and NI were positively correlated in a small number of gyri. CONCLUSION: The data suggest that there is significant degeneration of the frontal and temporal lobes in MSA, the lower laminae being affected more significantly than the upper laminae. Cortical degeneration in MSA is likely to be secondary to pathological changes occurring within subcortical areas.

Quantification of the pathological changes with laminar depth in the cortex in sporadic Creutzfeldt-Jakob disease

The laminar distribution of the vacuolation ('spongiform change'), surviving neurons, glial cell nuclei, and prion protein (PrP) deposits was studied in the frontal, parietal and temporal cortex in 11 cases of sporadic Creutzfeldt-Jakob disease (CJD). The distribution of the vacuolation was mainly bimodal with peaks of density in the upper and lower cortical laminae. The density of surviving neurons was greatest in the upper cortex while glial cell nuclei were distributed largely in the lower cortex. PrP deposits exhibited either a bimodal distribution or reached a maximum density in the lower cortex. The vertical density of the vacuoles was positively correlated with the surviving neurons in 12/44 of cortical areas studied, with glial cell nuclei in 16/44 areas and with PrP deposition in 15/28 areas. PrP deposits were positively correlated with glial cell nuclei in 12/31 areas. These results suggest that in sporadic CJD: (1) the lower cortical laminae are the most affected by the pathological changes; (2) the development of the vacuolation may precede that of the extracellular PrP deposits and the glial cell reaction; and (3) the pathological changes may develop initially in the lower cortical laminae and spread to affect the upper cortical laminae. © 2001 Elsevier Science Ireland Ltd. All rights reserved.

Laminar degeneration of the frontal and temporal cortex in neuronal intermediate filament inclusion disease (NIFID): a study using a-internexin immunohistochemistry

Objective: To determine the laminar distribution of the pathological changes in the frontal and temporal lobe in neuronal intermediate filament inclusion disease (NIFID). Method: The distribution of the alpha-intenexin-positive neuronal cytoplasmic inclusions (NCI), surviving neurons, swollen achromatic neurons (SN) and glial cell nuclei was studied across the cortex in gyri of the frontal and temporal lobe in 10 cases of NIFID. Results: The distribution of the NCI was highly variable within different gyri, a peak in the upper cortex, a bimodal distribution with peaks of density in the upper and lower laminae, or no significant variation in density across the cortex. The surviving neurons were either bimodally distributed or exhibited no significant change in density across the cortex. The SN and glial cell nuclei were most abundant in the lower cortical laminae. In half of the gyri, variations in density of the NCI across the cortex were positively correlated with the SN. In some gyri, the surviving neurons were positively correlated with the SN and negatively correlated with the glial cell nuclei. In addition, the SN and glial cell nuclei were positively correlated in over half the gyri studied. Conclusion: The data suggest that frontal and temporal lobe degeneration in NIFID characterized by NCI, SN, neuronal loss and gliosis extends across the cortical laminae with considerable variation between cases and gyri. alpha-internexin-positive neurons in the upper laminae appear to be particularly vulnerable. The gliosis appears to be largely correlated with the appearance of SN and with neuronal loss and not related to the NCI.

Laminar distribution of the pathological changes in the cerebral cortex in variant Creutzfeldt-Jakob disease (vCJD)

To determine the pattern of cortical degeneration in cases of variant Creutzfeldt-Jakob disease (vCJD), the laminar distribution of the vacuolation ("spongiform change"), surviving neurones, glial cell nuclei, and prion protein (PrP) deposits was studied in the frontal, parietal and temporal lobes. The vacuolation exhibited two common patterns of distribution: either the vacuoles were present throughout the cortex or a bimodal distribution was present with peaks of density in the upper and lower cortical laminae. The distribution of the surviving neurones was highly variable in different regions; the commonest pattern being a uniform distribution with cortical depth. Glial cell nuclei were distributed largely in the lower cortical laminae. The non-florid PrP deposits exhibited either a bimodal distribution or exhibited a peak of density in the upper cortex while the florid deposits were either uniformly distributed down the cortex or were present in the upper cortical laminae. In a significant proportion of areas, the density of the vacuoles was positively correlated with either the surviving neurones or with the glial cell nuclei. These results suggest similarities and differences in the laminar distributions of the pathogenic changes in vCJD compared with cases of sporadic CJD (sCJD). The laminar distribution of vacuoles was more extensive in vCJD than in sCJD whereas the distribution of the glial cell nuclei was similar in the two disorders. In addition, PrP deposits in sCJD were localised mainly in the lower cortical laminae while in vCJD, PrP deposits were either present in all laminae or restricted to the upper cortical laminae. These patterns of laminar distribution suggest that the process of cortical degeneration may be distinctly different in vCJD compared with sCJD.

Laminar distribution of the pathological changes in sporadic and variant Creutzfeldt-Jakob disease

The laminar distributions of the pathological changes in the cerebral cortex were compared in the prion diseases sporadic Creutzfeldt-Jakob disease (sCJD) and variant CJD (vCJD). First, in some cortical regions the vacuolation (‘spongiform change’) was more generally distributed across the cortex in sCJD. Second, there was greater neuronal loss in the upper cortex in vCJD and in the lower cortex in sCJD. Third, the ‘diffuse’ and ‘florid’ prion protein (PrPsc) deposits were more frequently distributed in the upper cortex in vCJD and the ‘synaptic’ deposits in the lower cortex in sCJD. Fourth, there was a significant gliosis mainly affecting the lower cortex of both disorders. The data suggest that the pattern of cortical degeneration is different in sCJD and vCJD which may reflect differences in aetiology and the subsequent spread of prion pathology in the brain.

Laminar distribution of Pick bodies, Pick cells and Alzheimer disease pathology in the frontal and temporal cortex in Pick's disease

Lesions in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) have distinct laminar distributions in the cortex. The objective of the present study was to test the hypothesis that the lesions characteristic of Pick's disease (PD) and AD have distinctly different laminar distributions in cases of PD. Hence, the laminar distribution of Pick bodies (PB), Pick cells (PC), senile plaques (SP) and neurofibrillary tangles (NFT) was studied in the frontal and temporal cortex in nine patients with PD. In 57% of analyses of individual cortical areas, the density of PB was maximal in the upper cortex while in 25% of analyses, the distribution of PB was bimodal with density peaks in the upper and lower cortex. The density of PC was maximal in the lower cortex in 77% of analyses while a bimodal distribution was present in 5% of analyses. The density of NFT was maximal in the upper cortex in 50% of analyses, in the lower cortex in 15% of analyses, with a bimodal distribution in 4% of analyses. The density of SP did not vary significantly with cortical depth in 86% of analyses. The vertical densities of PB and PC were negatively correlated in 12/21 (57%) of brain areas. The maximum density of PB in the upper cortex was positively correlated with the maximum density of PC in the lower cortex. In 17/25 (68%) of brain areas, there was no significant correlation between the vertical densities of PB and NFT. The data suggest that the pathogenesis of PB may be related to that of the PC. In addition, although in many areas PB and NFT occur predominantly in the upper cortex, the two lesions appeared to affect different neuronal populations.

Laminar distribution of amyloid-beta (Abeta) deposits in dementia with Lewy bodies: comparison with Alzheimer's disease

Significant amyloid-beta (Abeta) deposition in cases of dementia with Lewy bodies (DLB) may represent concurrent Alzheimer's disease (AD). To test this hypothesis, the laminar distribution of the diffuse, primitive, and classic Abeta deposits was studied in the frontal and temporal cortex in cases of DLB and were compared with AD. In DLB, the diffuse and primitive deposits exhibited two common patterns of distribution; either maximum density occurred in the upper cortical laminae or a bimodal distribution was present with density peaks in the upper and lower laminae. In addition, a bimodal distribution of the classic deposits was observed in approximately half of the cortical areas analysed. A number of differences in the laminar distributions of Abeta deposits were observed in DLB and AD. First, the proportion of the primitive relative to the diffuse and classic deposits present was lower in DLB compared with AD. Second, the primitive deposits were more frequently bimodally distributed in DLB. Third, the density of the diffuse deposits reached a maximum lower in the cortical profile in AD. These data suggest differences in the pattern of cortical degeneration in the two disorders and therefore, DLB cases with significant Abeta pathology may not represent the coexistence of DLB and AD.

Laminar distribution of ballooned neurons and tau positive neurons with inclusions in patients with corticobasal degeneration

The laminar distribution of ballooned neurons (BN) and tau positive neurons with inclusions (tau+ neurons) was studied in the frontal and temporal cortex in twelve patients with corticobasal degeneration (CBD). In the majority of brain areas, the density of BN and tau+ neurons was maximal in the lower and upper cortical laminae respectively. The densities of tau+ neurons in the upper and lower cortex were positively correlated. In the majority of brain areas, however, no correlations were observed between the densities of BN and tau+ neurons. The laminar distribution of the BN may reflect the degeneration of the feedback cortico-cortical and/or the efferent cortical pathways. By contrast, the distribution of the tau+ neurons may reflect the degeneration of the feed-forward cortico-cortical pathways. In addition, BN and tau+ neurons may arise as a result of distinct pathological processes.

Laminar distribution of cortical Lewy bodies and neurofibrillary tangles in dementia with Lewy bodies

The laminar distribution of Lewy bodies (LB) and neurofibrillary tangles (NFT) was studied in twelve cases of dementia with Lewy bodies (DLB). LB density was maximal in the lower cortex in 59% of cortical areas, in the upper cortex in 31% of areas while densities were similar in the upper and lower cortex in 9% of areas. The distribution of LB was either unimodal with a lower cortical peak, or bimodal with density peaks in the upper and lower cortex. The density of NFT was maximal in the upper cortex in all tissues. The distributions of LB and NFT were similar in temporal and frontal cortex and in cases with and without Alzheimer’s disease (AD). The vertical densities of LB and NFT were not significantly correlated. LB formation may affect the feedback cortico-cortical pathway and the efferent cortical projections whereas NFT formation may affect the feedforward cortico-cortical pathway.

Beta-amyloid (Abeta) deposits and blood vessels: laminar distribution in the frontal cortex of patients with Alzheimer’s disease

The laminar distribution of diffuse, primitive and classic beta-amyloid (Abeta) deposits and blood vessels was studied in the frontal cortex of patients with Alzheimer’s disease (AD). In most patients, the density of the diffuse and primitive Abeta deposits was greatest in the upper cortical layers and the classic deposits in the deeper cortical layers. The distribution of the larger blood vessels (>10 micron in diameter) was often bimodal with peaks in the upper and deeper cortical layers. The incidence of capillaries (<10 micron) was significantly higher in the deeper cortical layers in most patients. Multiple regression analysis selected vertical distance below the pia mater as the most significant factor correlated with the Abeta deposit density. With the exception of the classic deposits in two patients, there was no evidence that these vertical distributions were related to laminar variations in the incidence of large or small blood vessels.

Investigation of chaotic mixing in laminar fluid systems by the use of computational fluid dynamics

This work presents significant development into chaotic mixing induced through periodic boundaries and twisting flows. Three-dimensional closed and throughput domains are shown to exhibit chaotic motion under both time periodic and time independent boundary motions, A property is developed originating from a signature of chaos, sensitive dependence to initial conditions, which successfully quantifies the degree of disorder withjn the mixing systems presented and enables comparisons of the disorder throughout ranges of operating parameters, This work omits physical experimental results but presents significant computational investigation into chaotic systems using commercial computational fluid dynamics techniques. Physical experiments with chaotic mixing systems are, by their very nature, difficult to extract information beyond the recognition that disorder does, does not of partially occurs. The initial aim of this work is to observe whether it is possible to accurately simulate previously published physical experimental results through using commercial CFD techniques. This is shown to be possible for simple two-dimensional systems with time periodic wall movements. From this, and subsequent macro and microscopic observations of flow regimes, a simple explanation is developed for how boundary operating parameters affect the system disorder. Consider the classic two-dimensional rectangular cavity with time periodic velocity of the upper and lower walls, causing two opposing streamline motions. The degree of disorder within the system is related to the magnitude of displacement of individual particles within these opposing streamlines. The rationale is then employed in this work to develop and investigate more complex three-dimensional mixing systems that exhibit throughputs and time independence and are therefore more realistic and a significant advance towards designing chaotic mixers for process industries. Domains inducing chaotic motion through twisting flows are also briefly considered. This work concludes by offering possible advancements to the property developed to quantify disorder and suggestions of domains and associated boundary conditions that are expected to produce chaotic mixing.