Do β-amyloid (Aβ) deposits in patients with Alzheimer's disease and Down's syndrome grow according to the log-normal model?

The size frequency distributions of diffuse, primitive and classic β- amyloid (Aβ) deposits were studied in single sections of cortical tissue from patients with Alzheimer's disease (AD) and Down's syndrome (DS) and compared with those predicted by the log-normal model. In a sample of brain regions, these size distributions were compared with those obtained by serial reconstruction through the tissue and the data used to adjust the size distributions obtained in single sections. The adjusted size distributions of the diffuse, primitive and classic deposits deviated significantly from a log-normal model in AD and DS, the greatest deviations from the model being observed in AD. More Aβ deposits were observed close to the mean and fewer in the larger size classes than predicted by the model. Hence, the growth of Aβ deposits in AD and DS does not strictly follow the log-normal model, deposits growing to within a more restricted size range than predicted. However, Aβ deposits grow to a larger size in DS compared with AD which may reflect differences in the mechanism of Aβ formation.

The levels of neopterin, biopterin and the neopterin/biopterin ratio in urine from control subjects and patients with Alzheimer’s disease and Down’s syndrome

The levels of neopterin, biopterin and the neopterin/biopterin ratio (N/B) were measured in urine samples taken from normal young and elderly control subjects, exceptionally healthy elderly control subjects classified according to the ‘Senieur’ protocol and patients with Down’s syndrome (DS) or Alzheimer’s disease (AD). The N/B ratio was approximately unity in control groups with the exception of the normal elderly controls. The levels of neopterin and biopterin declined with age in the exceptionally healthy ‘Senieur’ control group. The N/B ratio was elevated in young and old DS patients as a result of the significant increase in neopterin. Neopterin levels were significantly elevated in AD patients compared with the healthy elderly controls, but this did not result in a significant increase in the N/B ratio in these patients. The N/B ratio increased with age in AD patients as a result of a decline in biopterin. These results suggested that there is a cellular immune reponse in DS and AD patients which in DS, may precede the formation of beta-amyloid deposits in the brain. In addition, there may be a deficiency in tetrahydrobiopterin biosynthesis in AD which becomes more marked with age.

A comparison of βamyloid (aβ deposition in the medial temporal lobe in late-onset sporadic Alzheimer's disease, and down's syndrome

The density of diffuse, primitive, classic and compact βamyloid (Aβ deposits was estimated in regions of the medial temporal lobe (MTL) in 15 cases of late-onset sporadic Alzheimer's disease (AD) and 12 cases of Down's syndrome (DS). A similar pattern of Aβ deposition was observed in the MTL in the AD and DS cases with a reduced density of deposits in the hippocampus compared with the adjacent cortical regions. Total Aβ deposit density was greater in DS than in AD in all brain regions examined. This could be attributable to overexpression of the amyloid precursor protein gene. The ratio of the primitive to the diffuse Aβ deposits was greater in DS than in AD which suggests that the formation of mature amyloid deposits is enhanced in DS. The diffuse deposits exhibited a parabolic and the primitive deposits an inverted parabolic response with age in the DS cases. This suggests either that the diffuse and primitive deposits are sequentially related or that there are alternate pathways of Aβ deposition. © 1995 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

Elevated urinary neopterin suggests immune activation in Alzheimer’s disease and Down’s syndrome

Neopterin, an unconjugated pteridine, is secreted in large quantities by activated macrophages and can be used as a clinical marker of activated cellular immunity in a patient. Hence, neopterin levels were measured in urine samples taken from patients with Down’s syndrome (DS), non-hospitalized and hospitalized Alzheimer’s disease (AD) and age and sex matched controls. All subjects and patients were free from infectious and malignant disease. A significant effect of age on urinary neopterin levels was found in control subjects, levels being greater in younger and older subjects. No significant trends with age were found in AD and DS patients. The mean level of neopterin was significantly increased in DS and AD compared with age matched controls suggesting immune activation in these patients. In DS, elevated neopterin levels were present in individuals at least 17yrs old suggesting that immune activation could be associated with the initial deposition of beta/A4 in the brain.

Alzheimer's disease and vision: a proposed new diagnostic test

A potential non-invasive neurobiological test for Alzheimer's disease has been recently proposed and published. This test is likely to be of considerable interest to optometrists as it involves measurements of pupil dilation. This article decsribes some of the controversial issues surrounding the clinical diagnosis of Alzheimer's disease and discusses the advantages, limitations, and implications of the new test.

Creutzfeldt-Jakob disease and vision

This article describes the symptoms and pathology associated with Creutzfeldt-Jakob disease and prion disease, how prion protein may cause disease and the visual aspects of prion diseases.

Variant Creutzfeldt-Jakob disease and the eye

Variant Creutzfeldt-Jakob disease (vCJD) was first described in the UK in 1996 and is one of a group of diseases, the transmissible spongiform encephalopathies (TSEs) which affect both animals and humans. This review discusses vCJD in the context of other TSEs, considers the controversial 'prion' hypothesis as to the cause of the disease, the ocular features of vCJD, and the possible transmission of the disease via optoetric devices.

Alzheimer’s disease and the eye

Dementia, including Alzheimer’s disease (AD), is a major disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of ß-amyloid (Aß) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary response to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances of complex visual functions such as reading, visuospatial function, and in the naming and identification of objects. Many of these changes are controversial with conflicting data in the literature and no ocular or visual feature can be regarded as particularly diagnostic of AD. In addition, some pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. The optometrist has a role in helping a patient with AD, if it is believed that signs and symptoms of the disease are present, so as to optimize visual function and improve the quality of life. (J Optom 2009;2:103-111 ©2009 Spanish Council of Optometry)

Creutzfeldt-Jakob disease and the eye

This article describes: 1) the symptoms and pathology of CJD, 2) how prion proteins may cause CJD, 3) the visual signs and symptoms of CJD, and 4) the scientific evidence which supports a possible transmission of CJD via optometric devices.

Studies on the outer membrane of Pseudomonas aeruginosa and associated resistance properties

The aim of this thesis was to investigate antibacterial agents for use in disinfectant formulation in conjunction with benzalkonium chloride (BKC), and if possible, to synthesise novel agents based upon successful structures. Development of resistance to antibacterial agents following long-term exposure of P. aeruginosa to BKC was also investigated, examining cross-resistance to clinically relevant antibiotics and determining mechanisms of resistance. In this study over 50 compounds were examined for antibacterial action against P. aeruginosa, both alone and in conjunction with BKC. Successful compounds were used to design novel agents, based upon the acridine ring structure, some of which showed synergy with BKC. In 15 of the 16 strains exposed to increasing concentrations of BKC, resistance to the disinfectant arose. Strains PAO1 and OO14 were examined further, each showing stable BKC resistance and a slightly varying profile of cross-resistance. In strain PAO1 alterations in the fatty acids of the cytoplasmic membrane, increase in expression of OprG, decrease in susceptibility to EDTA as an outer membrane permeabilising agent and an increase in negativity of the cell surface charge were observed as cells became more resistant to BKC. In strain OO14 a decrease in whole cell phosphatidylcholine content, a decrease in binding/uptake of BKC and an increase in cell surface hydrophobicity were observed as cells became more resistant to BKC. Resistance to tobramycin in strain OO14 was initially high, but fell as cells were adapted to BKC, this coincided with a quantitative reduction of plasmid DNA in the cells.

Antibiotic and biocide resistance in Salmonella enterica and Escherichia coli 0157

Bacterial resistance to antibiotics and biocides is a prevalent problem, which may be exacerbated by the commonplace and often unnecessary inclusion of biocides into domestic products. Addition of antimicrobials, to domestic disinfectants has raised concern about promoting microbial resistance and potential cross-resistance to therapeutic antibiotics. This study investigated the potential for resistance in Salmonella enterica serovars Enteritidis, Typhimurium, Virchow and Escherichia call 0157 to commonly used biocides, to identify mechanisms underlying resistance and whether these provided cross-resistance to antibiotics. Salmonella enterica and E. coli 0157 strains were serially exposed to sub-inhibitory. concentrations of erythromycin (ERY), benzalkonium chloride (BKC), chlorhexidine hydrochloride (CHX)and triclosan (TLN). Once resistance was achieved permeability changes in the outer membrane, including LPS, cell surface charge and hydrophobicityand the presence of,an active efflux were investigated as possible resistance candidates. Thin layer chromatography (TLC) and Gas chromatography (GC) were carried out to examine fatty acid and lipid changes in E. coli 0157 isolates with reduced susceptibility to TLN. Cross-resistance was studied by the Stoke's method and standard microdilution assays. Examination of the outer membrane proteins and LPS did not reveal any significant changes between parent and resistant strains. The hydrophobicity of the cells increased as the cells were passaged and became less. susceptible. An active efflux system was the most likely mechanism of resistance in all strains tested and a fab1 mutation was associated with E. coli 0157 resistant to TLN isolates. In all isolates investigated the resistance was stable for over 30 passages in biocide-free media. A high degree of cross-resistance was obtained in TLN-resjstant Escherichia coli 0157 strains, which repeatedly exerted decreased susceptibility to various antimicrobials, including chloramphenicol, erythromycin, imipenem, tetracycline and trimethoprirn:, as well as to various biocides. The results of this laboratory-based investigation suggest that it is possible for microorganisms to become resistant to biocides when repeatedly exposed to sublethal concentrations. This may be especially the case in the domestic environment where administration of biocides is poorly controlled. Eventually it could lead to the undesirable situation of resident strains becoming resistant to disinfection and cross resistant to other antimicrobials.