Spatial correlations between beta-amyloid (Abeta) deposits and blood vessels in early-onset Alzheimer's disease

In cases of late-onset Alzheimer’s disease (AD), there is a spatial correlation between the classsic ‘cored’ type of Beta-amyloid (Abeta) deposit and the large vertically penetrating arterioles in the cerebral cortex suggesting that blood vessels are involved in the pathogenesis of the classic deposits. In this chapter, the spatial correlations between the diffuse, primitive, and classic Abeta deposits and blood vessels were studied in 10 cases of early-onset AD in the age range 40 – 65 years. Sections of frontal cortex were immunostained with antibodies against Abeta?and with collagen IV to reveal the Abeta deposits and blood vessel profiles. In the early-onset cases as a whole, all types of Abeta? deposit and blood vessel profiles were distributed in clusters. There was a positive spatial correlation between the clusters of the diffuse Abeta deposits and the larger (>10µm) and smaller diameter (<10?m) blood vessel profiles in one and three cases respectively. The primitive and classic Abeta deposits were spatially correlated with larger and smaller blood vessels both in three and four cases respectively. Spatial correlations between the Abeta deposits and blood vessels may be more prevalent in cases expressing amyloid precursor protein (APP) than presenilin 1 (PSEN1) mutations. Apolipoprotein E (Apo E) genotype of the patient did not appear to influence the spatial correlation with blood vessel profiles. The data suggest that the larger diameter blood vessels are less important in the pathogenesis of the classic Abeta deposits in early-onset compared with late-onset AD.

The spatial patterns of pathological brain lesions in 12 patients with corticobasal degeneration

Corticobasal degeneration (CBD) is a rare and progressive neurological disorder characterised by the presence of ballooned neurons (BN) and tau positive inclusions in neurons and glial cells. We studied the spatial patterns of the BN, tau positive neurons with inclusions (tau + neurons), and tau positive plaques in the neocortex and hippocampus in 12 cases of CBD. All lesions were aggregated into clusters and in many brain areas, the clusters were distributed in a regular pattern parallel to the tissue boundary. In the majority of cortical areas, the clusters of BN were larger in the lower compared with the upper laminae while the clusters of tau + neurons were larger in the upper laminae. Clusters of BN and tau + neurons were either negatively correlated or not significantly correlated in the upper and lower cortical laminae. Hence, BN and tau + lesions in CBD exhibit similar spatial patterns as lesions in Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Pick's disease (PD). The location, sizes and distribution of the clusters in the neocortex suggest that the tau + lesions may be associated with the degeneration of the feedforward and the BN the feedback cortico-cortical and/or the efferent cortical pathways. © 2001 Elsevier Science Ireland Ltd. All rights reserved.

The spatial patterns of prion protein deposits in Creutzfeldt-Jakob disease:Comparison with β-amyloid deposits in Alzheimer's disease

Similar pathological processes may be involved in the deposition of extracellular proteins in the brains of patients with Creutzfeldt-Jakob disease (CJD) and Alzheimer's disease (AD). Hence, this study compared the spatial patterns of prion protein (PrP) deposits in the cerebral cortex and hippocampus in cases of sporadic CJD with those of β-amyloid (Aβ) deposits in sporadic AD. PrP and Aβ deposits were aggregated into clusters and, in 90% of brain areas in CJD and 57% in AD, the clusters were regularly distributed parallel to the tissue boundary. In a significant proportion of cortical analyses, the mean diameter of the clusters of PrP and Aβ deposits were similar to those of the cells of origin of the cortico-cortical pathways. Aβ deposits in AD were distributed more frequently in larger-sized clusters than PrP deposits in CJD. In addition, in the hippocampus and dentate gyrus, clustering of Aβ deposits was observed in AD but PrP deposits were rare in these regions in CJD. The size, location and distribution of the extracellular protein deposits within the cortex of both disorders was consistent with the degeneration of the cortico-cortical pathways. Furthermore, spread of the pathology along these pathways may be a pathogenic feature common to CJD and AD. © 2001 Elsevier Science Ireland Ltd.

Spatial aspects of MRSA epidemiology:A case study using stochastic simulation, kernel estimation and SaTScan

The identification of disease clusters in space or space-time is of vital importance for public health policy and action. In the case of methicillin-resistant Staphylococcus aureus (MRSA), it is particularly important to distinguish between community and health care-associated infections, and to identify reservoirs of infection. 832 cases of MRSA in the West Midlands (UK) were tested for clustering and evidence of community transmission, after being geo-located to the centroids of UK unit postcodes (postal areas roughly equivalent to Zip+4 zip code areas). An age-stratified analysis was also carried out at the coarser spatial resolution of UK Census Output Areas. Stochastic simulation and kernel density estimation were combined to identify significant local clusters of MRSA (p<0.025), which were supported by SaTScan spatial and spatio-temporal scan. In order to investigate local sampling effort, a spatial 'random labelling' approach was used, with MRSA as cases and MSSA (methicillin-sensitive S. aureus) as controls. Heavy sampling in general was a response to MRSA outbreaks, which in turn appeared to be associated with medical care environments. The significance of clusters identified by kernel estimation was independently supported by information on the locations and client groups of nursing homes, and by preliminary molecular typing of isolates. In the absence of occupational/ lifestyle data on patients, the assumption was made that an individual's location and consequent risk is adequately represented by their residential postcode. The problems of this assumption are discussed, with recommendations for future data collection.

Analysis of spatial patterns in histological sections of brain tissue using a method based on regression

A method of determining the spatial pattern of any histological feature in sections of brain tissue which can be measured quantitatively is described and compared with a previously described method. A measurement of a histological feature such as density, area, amount or load is obtained for a series of contiguous sample fields. The regression coefficient (β) is calculated from the measurements taken in pairs, first in pairs of adjacent samples and then in pairs of samples taken at increasing degrees of separation between them, i.e. separated by 2, 3, 4,..., n units. A plot of β versus the degree of separation between the pairs of sample fields reveals whether the histological feature is distributed randomly, uniformly or in clusters. If the feature is clustered, the analysis determines whether the clusters are randomly or regularly distributed, the mean size of the clusters and the spacing of the clusters. The method is simple to apply and interpret and is illustrated using simulated data and studies of the spatial patterns of blood vessels in the cerebral cortex of normal brain, the degree of vacuolation of the cortex in patients with Creutzfeldt-Jacob disease (CJD) and the characteristic lesions present in Alzheimer's disease (AD). Copyright (C) 2000 Elsevier Science B.V.

The spatial pattern of the vacuolation in patients with sporadic Creutzfeldt-Jakob disease

The spatial pattern of the vacuolation ('spongiform change') was studied in the upper and lower laminae of the cerebral cortex, the CA1/CA2 sectors of the hippocampus and the molecular layer of the cerebellum in 11 cases of sporadic Creutzfeldt-Jakob disease (CJD). Individual vacuoles were grouped into clusters, 50 to >1600 μm in diameter and, in the majority of tissue sections, the vacuole clusters were distributed with regular periodicity parallel to the tissue boundary. The size of the vacuole clusters was positively correlated with patient age in the lower laminae of the occipital cortex and the inferior temporal gyrus (ITG) and negatively correlated with age in the hippocampus. In addition, the size of the vacuole clusters was positively correlated with disease duration in the upper laminae of the ITG. The size and distribution of the vacuole clusters suggests that the vacuolation in CJD reflects the degeneration of specific brain pathways and supports the hypothesis that prion pathology may spread through the brain along well defined anatomical pathways. (C) 2000 Elsevier Science Ireland Ltd.

The spatial patterns of the tau immunopositive neuronal cytoplasmic inclusions (NCI) in the tauopathies

Tau positive neuronal cytoplasmic inclusions (NCI) are the ‘hallmark’ pathological feature of several neurodegenerative diseases collectively known as the tauopathies. This study compared the spatial patterns of various types of NCI in selected tauopathies including the neurofibrillary tangles (NFT) in Alzheimer's disease (AD) and progressive supranuclear palsy (PSP), Pick bodies (PB) in Pick’s disease (PiD), and the tau positive (tau+) neurons in corticobasal degeneration (CBD). In the cerebral cortex of these disorders, the tau+ NCI were distributed in clusters and in a significant proportion of analyses, the clusters were distributed with a regular periodicity parallel to the pia mater. The inclusions in AD, PiD and CBD exhibited a similar range of spatial patterns but in PSP were less frequently clustered and more frequently randomly distributed. In gyri where the NCI were clustered, there was a significant difference in mean cluster size between disorders. Hence, clusters of NFT in AD were larger than those in PSP and the tau+ neurons in CBD and clusters of PB in PiD were larger than the tau+ neurons in CBD and the NFT in PSP. The cluster size of the tau+ neurons in CBD was similar to the NFT in PSP. The data suggest that the formation of clusters of NCI, regularly distributed parallel to the pia mater, is a common feature of the tauopathies indicating similar patterns of cortical degeneration and pathogenic mechanisms across different diseases. Furthermore, the data suggest that cortical degeneration affecting the short and long cortico-cortical pathways may be a characteristic of the tauopathies.

Density and spatial pattern of the neuropathological changes in the cerebellum in the prion disease variant Creutzfeldt-Jakob disease (vCJD)

The objective of this chapter is to quantify the neuropathology of the cerebellar cortex in cases of the prion disease variant Creutzfeldt-Jakob disease (vCJD). Hence, sequential sections of the cerebellum of 15 cases of vCJD were stained with H/E, or immunolabelled with a monoclonal antibody 12F10 against prion protein (PrP) and studied using quantitative techniques and spatial pattern analysis. A significant loss of Purkinje cells was evident in all cases. Densities of the vacuolation and the protease resistant form of prion protein (PrPSc) in the form of diffuse and florid plaques were greater in the granule cell layer (GL) than the molecular layer (ML). In the ML, vacuoles and PrPSc plaques, occurred in clusters which were regularly distributed along the folia, larger clusters of vacuoles and diffuse plaques being present in the GL. There was a negative spatial correlation between the vacuoles and the surviving Purkinje cells in the ML and a positive spatial correlation between the clusters of vacuoles and the diffuse PrPSc plaques in the ML and GL in five and six cases respectively. A canonical variate analysis (CVA) suggested a negative correlation between the densities of the vacuolation in the GL and the diffuse PrPSc plaques in the ML. The data suggest: 1) all laminae of the cerebellar cortex were affected by the pathology of vCJD, the GL more severely than the ML, 2) the pathology was topographically distributed especially in the Purkinje cell layer and GL, 3) pathological spread may occur in relation to a loop of anatomical projections connecting the cerebellum, thalamus, cerebral cortex, and pons, and 4) there are differences in the pathology of the cerebellum in vCJD compared with the M/M1 subtype of sporadic CJD (sCJD).

Advanced data driven visualisation for geo-spatial data

Most current 3D landscape visualisation systems either use bespoke hardware solutions, or offer a limited amount of interaction and detail when used in realtime mode. We are developing a modular, data driven 3D visualisation system that can be readily customised to specific requirements. By utilising the latest software engineering methods and bringing a dynamic data driven approach to geo-spatial data visualisation we will deliver an unparalleled level of customisation in near-photo realistic, realtime 3D landscape visualisation. In this paper we show the system framework and describe how this employs data driven techniques. In particular we discuss how data driven approaches are applied to the spatiotemporal management aspect of the application framework, and describe the advantages these convey. © Springer-Verlag Berlin Heidelberg 2006.

The spatial patterns of β-amyloid (Aβ) deposits and neurofibrillary tangles (NFT) in late-onset sporadic Alzheimer's disease

The spatial patterns of β-amyloid (Aβ) deposits and neurofibrillary tangles (NFT) were studied in areas of the cerebral cortex in 16 patients with the late-onset, sporadic form of Alzheimer's disease (AD). Diffuse, primitive, and classic Aβ deposits and NFT were aggregated into clusters; the clusters being regularly distributed parallel to the pia mater in many areas. In a significant proportion of regions, the sizes of the regularly distributed clusters approximated to those of the cells of origin of the cortico-cortical projections. The diffuse and primitive Aβ deposits exhibited a similar range of spatial patterns but the classic Aβ deposits occurred less frequently in large clusters >6400m. In addition, the NFT often occurred in larger regularly distributed clusters than the Aβ deposits. The location, size, and distribution of the clusters of Aβ deposits and NFT supports the hypothesis that AD is a 'disconnection syndrome' in which degeneration of specific cortico-cortical and cortico-hippocampal pathways results in synaptic disconnection and the formation of clusters of NFT and Aβ deposits. © 2011 Nova Science Publishers, Inc.

Crowdsourcing, citizen science or volunteered geographic information? The current state of crowdsourced geographic information

Citizens are increasingly becoming an important source of geographic information, sometimes entering domains that had until recently been the exclusive realm of authoritative agencies. This activity has a very diverse character as it can, amongst other things, be active or passive, involve spatial or aspatial data and the data provided can be variable in terms of key attributes such as format, description and quality. Unsurprisingly, therefore, there are a variety of terms used to describe data arising from citizens. In this article, the expressions used to describe citizen sensing of geographic information are reviewed and their use over time explored, prior to categorizing them and highlighting key issues in the current state of the subject. The latter involved a review of 100 Internet sites with particular focus on their thematic topic, the nature of the data and issues such as incentives for contributors. This review suggests that most sites involve active rather than passive contribution, with citizens typically motivated by the desire to aid a worthy cause, often receiving little training. As such, this article provides a snapshot of the role of citizens in crowdsourcing geographic information and a guide to the current status of this rapidly emerging and evolving subject.

Spatial patterns of neuronal cytoplasmic inclusions in the tauopathies: A comparative study of five disorders

The tauopathies are a major molecular group of neurodegenerative disorders characterised by the deposition of abnormal cellular aggregates of the microtubule associated protein (MAP) tau in the form of neuronal cytoplasmic inclusions (NCI). Recent research suggests that cell to cell propagation of pathogenic tau may be involved in the neurodegeneration of these disorders. If pathogenic tau spreads along anatomical pathways it may give rise to specific spatial patterns of the NCI in brain tissue. To test this hypothesis, the spatial patterns of NCI in cerebral cortical regions were compared in tissue sections taken from five major tauopathies: (1) argyrophilic grain disease (AGD), (2) Alzheimer's disease (AD), (3) corticobasal degeneration (CBD), (4) Pick's disease (PiD), and (5) progressive supranuclear palsy (PSP). In the cerebral cortex of these disorders, NCI were frequently aggregated into clusters and the clusters were regularly distributed parallel to the pia mater. In a significant proportion of regions, the mean size of the regularly distributed clusters of NCI was in the range 400 – 800 m, measured parallel to the pia mater, approximating to the dimension of cell columns associated with the cortico-cortical anatomical pathways. Hence, the data suggest that cortical NCI in the tauopathies exhibit a spatial pattern in the cortex which could result from the spread of pathogenic tau along anatomical pathways. Treatments designed to protect the cortex from tau propagation may therefore be applicable across several different disorders within this molecular group.