Dispersion of classic beta-amyloid deposits around blood vessels in Alzheimer’s disease

The spatial pattern of the classic (‘cored’) type of beta-amyloid (Abeta) deposit was studied in the upper laminae of the superior temporal gyrus in 9 cases of sporadic Alzheimer’s disease (SAD). Abeta stained tissue was counterstained with collagen IV to study the relationships between the spatial distribution of the classic deposits and the blood vessel profiles. Both the classic deposits and blood vessel profiles were distributed in clusters. In all cases, there was a spatial correlation between the clusters of the classic deposits and the larger diameter (>10 micron) blood vessel profiles and especially the vertically penetrating arterioles. In only 1 case, was there a significant spatial correlation between the clusters of the classic deposits and the smaller diameter (<10 micron) capillaries. In 9/11 cases, the clusters of the classic deposits were significantly larger than those of the clusters of the larger blood vessels. In addition, the density of the classic deposits declined as a negative exponential function with distance from the vertically penetrating arterioles. These results suggest that the classic Abeta deposits cluster around the larger blood vessels in the frontal cortex and that diffusion of proteins from these blood vessels could be involved in the pathogenesis of the classic deposits in SAD.

Degeneration of cortical neurons associated with diffuse beta-amyloid (Abeta) deposits in Alzheimer’s disease

The frequency of morphological abnormalities in neuronal perikarya which were in contact with diffuse beta-amyloid (Abeta) deposits in patients with Alzheimer’s disease (AD) was compared with neurons located adjacent to the deposits. Morphological abnormalities were also studied in elderly, non-demented (ND) cases with and without diffuse Abeta deposits. In AD and ND cases with Abeta deposits, an increased proportion of neurons in contact with diffuse deposits exhibited at least one abnormality compared with neurons located adjacent to the deposits. Neurons in contact with diffuse deposits exhibited a greater frequency of abnormalities of shape, nuclei, nissl substance and had a higher frequency of cytoplasmic vacuoles compared with adjacent neurons. A greater frequency of abnormalities of shape, nissl substance and in the frequency of displaced nuclei were also observed in neurons adjacent to diffuse deposits in AD compared with ND cases. With the exception of absent nuclei, morphological abnormalities adjacent to diffuse deposits in ND cases were similar to those of ND cases without Abeta deposits. These results suggest that neuronal degeneration is associated with the earliest stages of Abeta deposit formation and is not specifically related to the formation of mature senile plaques.

The spatial pattern of beta-amyloid (Abeta) deposits in Alzheimer’s disease patients is related to apolipoprotein genotype

The spatial patterns of the diffuse, primitive, and classic beta-amyloid (Abeta) deposits was studied in the frontal and temporal cortex in cases of Alzheimer’s disease (AD) expressing different apolipoprotein (Apo E) genotypes. No significant differences in the density of the three Abeta deposit subtypes were observed in individuals expressing genotypes e2/3 and e3/3 compared with those expressing e3/4 and e4/4. In all patients, Abeta deposit subtypes occurred in the tissue in clusters. Chi-square contingency analyses of the data suggested that the cluster size of the diffuse and classic Abeta deposits was unrelated to Apo E genotype. However, the primitive (‘neuritic’) type Abeta deposits occurred more frequently in smaller, denser clusters in individuals expressing genotypes e3/4 and e4/4 compared with those expressing e2/3 and e3/3. Hence, the presence of the e4 allele may be associated with a more specific pattern of neuronal degeneration in the frontal and temporal cortex in AD.

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.

The spatial patterns of beta-amyloid (Abeta) deposits in elderly non-demented patients and patients with Alzheimer’s disease

The spatial patterns of diffuse, primitive, classic and compact beta-amyloid (Abeta) deposits were studied in the medial temporal lobe in 14 elderly, non-demented patients (ND) and in nine patients with Alzheimer’s disease (AD). In both patient groups, Abeta deposits were clustered and in a number of tissues, a regular periodicity of Abeta deposit clusters was observed parallel to the tissue boundary. The primitive deposit clusters were significantly larger in the AD cases but there were no differences in the sizes of the diffuse and classic deposit clusters between patient groups. In AD, the relationship between Abeta deposit cluster size and density in the tissue was non-linear. This suggested that cluster size increased with increasing Abeta deposit density in some tissues while in others, Abeta deposit density was high but contained within smaller clusters. It was concluded that the formation of large clusters of primitive deposits could be a factor in the development of AD.

The relationship between senile plaques, neurofibrillary tangles and amyloid (A4) deposits in Alzheimer’s disease: A Principal Components Analysis

A Principal Components Analysis (PCA) was carried out on the density of lesions revealed by different stains in a total of 47 brain regions from six elderly patients with Alzheimer’s disease (AD). The aim was to determine the relationships between the density of senile plaques (SP) revealed by the Glees and Gallyas stains and A4 deposits and between the plaques and neurofibrillary tangles (NFT) in the same brain region. The analysis indicated that the populations of plaques revealed by the Glees and Gallyas stains were closely related to the A4 protein deposits but none of the lesions were related to NFT. The data suggest: 1) that neocortical regions differ from the hippocampus in the relative development of A4 and NFT; the former having more A4 deposits and the latter more NFT and 2) that the processes that lead to the formation of SP and NFT occur independently of each other in the same brain region.

The density of mature beta/A4 deposits is enhanced in Alzheimer's disease cases with pronounced congophilic angiopathy

The density of diffuse, primitive, classic and compact beta/A4 deposits was estimated in the cortex and hippocampus in Alzheimer's disease (AD) cases with pronounced congophilic angiopathy (CA). The total density of beta/A4 deposits in a brain region was similar in cases with and without CA. Significantly fewer diffuse deposits and more primitive/classic deposits were found in the cases with CA. The density of the primitive, classic and compact deposits were positively correlated in the cases without CA. However, no correlations were observed between the density of the mature subtypes and the diffuse deposits in these cases. In cases with CA, the density of the primitive deposits was positively correlated with the diffuse deposits but not with the classic deposits. The data suggest that the mature beta/A4 deposits are derived from the diffuse deposits and that the presence of pronounced CA enhances their formation.

Relationships between beta-amyloid (Abeta) deposits and blood vessels in familial and sporadic Alzheimer's disease

Introduction: The density of diffuse, primitive and classic beta-amyloid (Abeta) deposits and blood vessels was studied in nine cases of sporadic Alzheimer's disease (SAD) and 10 cases of familial Alzheimer's disease (FAD) including two cases with amyloid precursor protein (APP) mutations (APP717, Val - Ile). Materials and Methods: Sections of frontal cortex stained for Abeta12-28 counterstained with collagen type IV antiserum. Densities measured along the upper cortex in 64-128, 1000 x 200 micron continuous sample fields. Results: The density of diffuse and primitive deposits was not correlated with blood vessels in FAD or SAD. The density of the classic deposits was positively correlated with the larger diameter (> 10 micron) blood vessels in all SAD cases and weakly correlated with blood vessel in three non-APP FAD cases. Conclusions: Blood vessels are less important in the formation of classic Abeta deposits in FAD compared with SAD.

Dispersion of prion protein deposits around blood vessels in variant Creutzfeldt-Jakob disease

In variant Creutzfeldt-Jakob disease (vCJD), a disease linked to bovine spongiform encephalopathy (BSE), florid-type prion protein (PrP(sc)) deposits are aggregated around the larger diameter (> 10 µm) cerebral microvessels. Clustering of PrP(sc) deposits around blood vessels may result from blood-borne prions or be a consequence of the cerebral vasculature influencing the development of the florid deposits. To clarify the factors involved, the dispersion of the florid PrP(sc) deposits was studied around the larger diameter microvessels in the neocortex, hippocampus, and cerebellum of ten cases of vCJD. In the majority of brain regions, florid deposits were clustered around the larger diameter vessels with a mean cluster size of between 50 µm and 628 µm. With the exception of the molecular layer of the dentate gyrus, the density of the florid deposits declined as a negative exponential function of distance from a blood vessel profile suggesting that diffusion of molecules from blood vessels is a factor in the formation of the florid deposits. Diffusion of PrP(sc) directly into the brain via the microvasculature has been demonstrated in vCJD in a small number of cases. However, the distribution of the prion deposits in vCJD is more likely to reflect molecular 'chaperones' diffusing from vessels and promoting the aggregation of pre-existing PrP(sc) in the vicinity of the vessels to form florid deposits.

Palaeozoic volcanogenic mineral deposits at Parys Mountain, Avoca, and S.E. Canada: a comparative study. Available in 2 volumes.

The sulphide mineralisation at Avoca and Parys Mountain is intimately related to volcanism and is of volcanogenic sedimentary type. The associated volcanics are predominantly pyroclastics of rhyodacitic composition and of Upper Ordovician age. They were erupted from discrete small volcanic centres, products of single local volcanic events, whose spatial distribution was related to fractures in the sialic basement of the paratectonic Caledonides of the British Isles. These fractures resulted in linear controls on volcanic, plutonic and tectonic features; they are the result of predominantly strikeslip stresses generated in this part of the European plate during closure of the Iapetus ocean. The mineralisation, predominantly pyritic, consists of a siliceous footwall zone containing bedded and cross-cutting sulphides and an overlying non-siliceous zone of bedded sulphides which may show vertical zoning of metal ratios. The sulphides are associated with chert and iron formation and have been affected by slumping. Mineralisation developed near the vents during intense fumarolic activity accompanying strong volcanism; at Parys Mountain, fumarolic activity commenced prior to, and continued after, the rnain volcanic event. Comparison with similar deposits in Newfoundland and at Bathurst, in the Canadian Appalachians, shows that mineralisation can be associated with any discrete pulse of acid magmatism in shallow subaqueous conditions. Local features of the sulphides and associated sediments are similar, although in more distal deposits (with respect to a volcanic centre) footwall alteration and mineralisation are less well developed. The nature of the basement and the presence or absence of earlier volcanics are not critical, although establishment of a local tensional regime at the time of ore formation may be important. The volcanics hosting mineralisation are rhyodacitic pyroclastics, generally related to a small centre and representing a single episode of volcanism.

Textural and microstructural studies of zinc sulfide and associated phases in certain base metal deposits

A textural and microstructural study of a variety of zinc sulfide-containing ores has been undertaken, and the possible depositional and deformational controls of textural and microstructural development considered. Samples for the study were taken from both deformed and undeformed zinc ores of the Central U.S. Appalachians, and deformed zinc ores of the English Pennines. A variety of mineralogical techniques were employed, including transmitted and reflected light microscopy of etched and unetched material, transmission electron microscopy and electron microprobe analysis. For the Pennine zinc sulfides, spectroscopic, x-ray diffraction and fluid inclusion studies were also undertaken. Optical and electron optical examination of the Appalachian material confirmed the suitability of zinc sulfide for detailed study with such techniques. Growth and deformation-related microstructures could be distinguished from specimen-preparation induced artifacts. A deformationally-mduced lamelliform optical anisotropy is seen to be developed in areas hosting a dense planar microstructure of {111} twin- and slip-planes. The Pennine zinc sulfide texturally records a changing depositional environment. Thus, for example, delicately growth- zoned crystals are truncated and cross-cut by solution disconformities. Fluid inclusion studies indicate a highly saline (20-25 wt. % equiv. NaCl), low temperature (100-150°C.) fluid. Texturally, two varieties of zinc sulfide can be recognised; a widely developed, iron- banded variety, and a paragenetically early variety, banded due to horizons rich in crystal defects and microscopic inclusions. The zinc sulfide takes the form of a disordered 3C-polytype, with much of the disorder being deformational in origin. Twin- and slip-plane fabrics are developed . A deformation-related optical anisotropy is seen to overprint growth-related anisotropy, along with cuprian alteration of certain {111} deformation planes.

Study of the deposition, properties and applications of electroless deposits containing particles

The deposition efficiencies of a number of electroless nickel and cobalt plating solutions were studied and in the case of nickel compared with a commercial plating solution Nifoss 80. At the optimum plating conditions (92ºC and pH 4.5) Nifoss 80 produced nickel layers most efficiently, the alkaline cobalt solution operated most efficiently at 90ºC and pH 9. The methods of producing compostte layers containing 2-3 µm carbide particles and chromium powder is described. Nickel and cobalt layers containing approximately 27% carbide particles, or 40% (Ni) and 30% (Co) chromium particles by volume were obtained. This value is independent of the particle concentration in the plating solution within the range (20~200 g/l). Hardness of the nickel. as deposited was 515 Hv, this was increased to a maximum of 1155 Hv by heat treatment at 200ºC for 5 hours in vacuum. Incorporation. of .chromium carbide particles resulted in a maximum hardness of 1225 Hv after heating at 500ºC for 5 hours in vacuum and chromium particles resulted in a maximum hardness of 16S0 Hv after heat treatment at 400ºC for 2 hours in vacuum. Similarly the hardness of cobalt as deposited was 600 Hv, this was increased to a maximum of 1300 Hv after heat treatment at 400ºC for 1 hour. Incorporation of chromium carbide particles resulted jn a maximum hardness of 1405 Hv after heating at 400ºC for 5 hours in vacuum and chromium particles resulted in a maximum hardness of 1440 Hv after. heat treating for 2 hours at 400ºC in vacuum. The structure of the deposits was studied by optical and scanning electron microscopy. The wear rate and coefficient of friction was determined by a pin and disc method. Wear rate and coefficient of friction decreased with increase in hardness. The wear resistance of the materials was also determined using a simulated forging test. Dies made of standard die steel were coated and the wear rates of the layers as deposited and after heat treatment were compared with those of uncoated tools. The wear resistance generally increased with hardness, it was 50-75% more than the uncoated die steel. Acetic acid salt spray test and outdoor exposure for six months was used to study the corrosion behaviour of the deposits and potentiodynamic curves plotted to find their corrosion potential. Nickel deposit exhibited less staining than carbide composite deposits and nickel-chromium deposits had the most noble corrosion potential.

Density and spatial pattern of β-amyloid (Aβ) deposits in corticobasal degeneration

Corticobasal degeneration (CBD) is a rare, progressive movement disorder characterized neuropathologically by widespread neuronal and glial pathology including tau-immunoreactive neuronal cytoplasmic inclusions (NCI), oligodendroglial inclusions (GI), and astrocytic plaques (AP). However, ß -amyloid (A ß) deposits have been observed in the cerebral cortex and/or hippocampus in some cases of CBD. To clarify the role of Aß deposition in CBD, the densities and spatial patterns of the Aß deposits were studied in three cases. In two cases, expressing apolipoprotein E (APOE) genotypes 2/3 or 3/3, the densities of the Aß deposits were similar to those in normal elderly brain. In the remaining case, expressing APOE genotype 3/4, Aß deposition was observed throughout the cerebral cortex, sectors CA1 and CA2 of the hippocampus, and the molecular layer of the dentate gyrus. The densities of the Aß deposits in this case were typical of those observed in Alzheimer's disease (AD). In the three cases, clustering of Aß deposits, with clusters ranging in size from 200 to >6400 µm in diameter, was evident in 25/27 (93%) of analyses. In addition, the clusters of Aß deposits were regularly distributed parallel to the tissue boundary in 52% of analyses, a spatial pattern similar to that observed in AD. These results suggest: (1) in some CBD cases, Aß pathology is age-related, (2) more extensive Aß deposition is observed in some cases, the density and spatial patterns of the Aß deposits being similar to AD, and (3) extensive deposition of Aß in CBD may be associated with APOE allele e4.