Amyloid and tau in the brain in sporadic Alzheimer's disease: defining the chicken and the egg

In the October 2013 issue of Acta Neuropathologica there were three very interesting articles on: Amyloid or tau: the chicken or the egg? In the first article, David Mann and John Hardy argued that the deposition of aggregated amyloid β (Aβ) protein in the brain is a primary driving force behind the pathogenesis of Alzheimer’s disease with tau pathology following as a consequential or at least a secondary event. In the communication that followed, Braak and Del Tredici presented the contrary argument with accumulation of tau protein as the primary event in sporadic Alzheimer’s disease. Attems and Jellinger questioned the concept of a chicken and egg and suggested that the majority of cases of age-associated dementia are not caused by one single primary pathological mechanism

Increased Aβ pathology in aged Tg2576 mice born to mothers fed a high fat diet

Maternal obesity is associated with increased risk of developing diabetes, obesity and premature death in adult offspring. Mid-life diabetes, hypertension and hypercholesterolaemia are risk factors for the development of sporadic Alzheimer's disease (AD). A key pathogenic feature of AD is the accumulation of β-amyloid (Aβ) in the brain. The purpose of this study was to investigate the effect of high fat diet feeding during early life on Aβ pathology in the Tg2576 mouse model of AD. Female mice were fed a standard (C) or high fat (HF) diet before mating and during gestation and lactation. At weaning, male offspring were fed a C diet. Significantly higher levels of guanidine-soluble Aβ and plaque loads were observed in the hippocampi of 11-month old Tg2576 mice born to mothers fed a HF diet. Changes in the extracellular matrix led to increased retention of Aβ within the parenchyma. These data support a role for maternal and gestational health on the health of the aged brain and pathologies associated with AD and may provide a novel target for both the prevention and treatment of AD

Evaluating the relationship between amyloid-β and α-synuclein phosphorylated at Ser129 in dementia with Lewy bodies and Parkinson’s disease

INTRODUCTION: Lewy body and Alzheimer-type pathologies often co-exist. Several studies suggest a synergistic relationship between amyloid-β (Aβ) and α-synuclein (α-syn) accumulation. We have explored the relationship between Aβ accumulation and the phosphorylation of α-syn at serine-129 (pSer129 α-syn), in post-mortem human brain tissue and in SH-SY5Y neuroblastoma cells transfected to overexpress human α-syn. METHODS: We measured levels of Aβ40, Aβ42, α-syn and pSer129 α-syn by sandwich enzyme-linked immunosorbent assay, in soluble and insoluble fractions of midfrontal, cingulate and parahippocampal cortex and thalamus, from cases of Parkinson’s disease (PD) with (PDD; n = 12) and without dementia (PDND; n = 23), dementia with Lewy bodies (DLB; n = 10) and age-matched controls (n = 17). We also examined the relationship of these measurements to cognitive decline, as measured by time-to-dementia and the mini-mental state examination (MMSE) score in the PD patients, and to Braak tangle stage. RESULTS: In most brain regions, the concentration of insoluble pSer129 α-syn correlated positively, and soluble pSer129 α-syn negatively, with the levels of soluble and insoluble Aβ. Insoluble pSer129 α-syn also correlated positively with Braak stage. In most regions, the levels of insoluble and soluble Aβ and the proportion of insoluble α-syn that was phosphorylated at Ser129 were significantly higher in the PD and DLB groups than the controls, and higher in the PDD and DLB groups than the PDND brains. In PD, the MMSE score correlated negatively with the level of insoluble pSer129 α-syn. Exposure of SH-SY5Y cells to aggregated Aβ42 significantly increased the proportion of α-syn that was phosphorylated at Ser129 (aggregated Aβ40 exposure had a smaller, non-significant effect). CONCLUSIONS: Together, these data show that the concentration of pSer129 α-syn in brain tissue homogenates is directly related to the level of Aβ and Braak tangle stage, and predicts cognitive status in Lewy body diseases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-014-0077-y) contains supplementary material, which is available to authorized users

Initial assessment of triplex PCR assay application for detection of toxic dinoflagellates, Alexandrium species (Dinophyceae), in environmental samples

Includes bibliographical references (leaves. 23-28).The frequency and geographical range of hannful algal blooms (HABs) are believed to be on the increase, with adverse affects on marine and human health making the implementation of stringent controls governmg monitoring programmes commonplace. The South African monitoring programme was established in 1989 and relies upon microscopic identification of HAB species. Microscopic identification is labour-intensive, requiring a high level of taxonomic expertise, and could be considered impractical for routine monitoring where analysis of large numbers of samples is required. Novel monitoring techniques, focusing mainly on probe technology, are being developed for rapid, unequivocal identification and enumeration of HAB species. In this study, a triplex peR assay, incorporating a genus-specific ribosomal DNA primer designed from phylogenetic studies on local Alexandrium populations, was optimised for application to environmental samples and tested against natural assemblages containing Alexandrium minutum. Specific positive results were consistently generated for samples containing A. minutum. Samples absent of A. minuturn cells did not generate the Alexandrium-specific amplicon. The absolute detection limit of 440 A. minutum cells r1 for this assay was established. Effects of non-target cells on the sensitivity of the assay were also investigated: although a decrease in sensitivity was found, A. minutum cells could still be detected in the presence of 100 times more non-target cells. This assay has been shown to be a useful tool for unequivocal identification of A. minutum cells within local environmental samples

A Pilot Study Comparing Aortic Valve Area Estimates Derived from Fick Cardiac Output with Estimates Based on Cheetah-NICOM Cardiac Output.

Contains fulltext : 221539.pdf (publisher's version ) (Open Access)Cardiac output during cardiac catheterization is often estimated using the modified Fick method (CO(Fick)). In this proof-of-concept, prospective non-randomized study carried out in a single academic healthcare centre, we examined whether replacing CO(Fick) in the Gorlin formula with Cheetah-NICOM monitor cardiac output (CO(Cheetah)) could produce an accurate and precise estimate of aortic valve area in patients with severe aortic stenosis. In twenty-six subjects, CO(Fick) and CO(Cheetah) were obtained concurrently. A spot and 3-minute running average of CO(Cheetah) was used. Bland and Altman analysis was used to derive bias, 95% limits of agreement (LOA) and confidence intervals (CI). The mean difference (bias) between AVA(Cheetah) (average) and AVA(Fick) was 0.11 cm(2) and the 95% LOA were ±0.42 cm(2). The 95% CI of the bias was 0.02-0.2 cm(2). The bias and 95% LOA of AVA(Cheetah) (spot value) were 0.14 ± 0.42cm(2), with a 95% CI of 0.06-0.23 cm(2). No proportional bias was present. AVA(Cheetah) thus appears to be a reasonably accurate measure of AVA in patients with severe aortic stenosis compared to AVA(Fick) measured using a modified Fick CO. However, the limits of agreement were not narrow enough to consider AVA(Cheetah) and AVA(Fick) interchangeable