On POD analysis of PIV measurements applied to mixing in a stirred vessel with a shear thinning fluid

P.O.D. technique is applied to 2D P.I.V. data in the field of hydrodynamics in a mixing tank with a Rushton turbine and a shear thinning fluid. Classical eigen-value spectrum is presented and phase portrait of P.O.D. coefficients are plotted and analyzed in terms of trailing vortices. A spectrum of dissipation rate of kinetic energy is introduced and discussed. Length scales associated to each P.O.D. modes are proposed

MAPT R406W increases tau T217 phosphorylation in absence of amyloid pathology

OBJECTIVE: Tau hyperphosphorylation at threonine 217 (pT217) in cerebrospinal fluid (CSF) has recently been linked to early amyloidosis and could serve as a highly sensitive biomarker for Alzheimer\u27s disease (AD). However, it remains unclear whether other tauopathies induce pT217 modifications. To determine if pT217 modification is specific to AD, CSF pT217 was measured in AD and other tauopathies. METHODS: Using immunoprecipitation and mass spectrometry methods, we compared CSF T217 phosphorylation occupancy (pT217/T217) and amyloid-beta (Aβ) 42/40 ratio in cognitively normal individuals and those with symptomatic AD, progressive supranuclear palsy, corticobasal syndrome, and sporadic and familial frontotemporal dementia. RESULTS: Individuals with AD had high CSF pT217/T217 and low Aβ42/40. In contrast, cognitively normal individuals and the majority of those with 4R tauopathies had low CSF pT217/T217 and normal Aβ 42/40. We identified a subgroup of individuals with increased CSF pT217/T217 and normal Aβ 42/40 ratio, most of whom were MAPT R406W mutation carriers. Diagnostic accuracies of CSF Aβ 42/40 and CSF pT217/T217, alone and in combination were compared. We show that CSF pT217/T217 × CSF Aβ 42/40 is a sensitive composite biomarker that can separate MAPT R406W carriers from cognitively normal individuals and those with other tauopathies. INTERPRETATION: MAPT R406W is a tau mutation that leads to 3R+4R tauopathy similar to AD, but without amyloid neuropathology. These findings suggest that change in CSF pT217/T217 ratio is not specific to AD and might reflect common downstream tau pathophysiology common to 3R+4R tauopathies

Front Neurosci

Background: Anxiety is common in patients with cognitive impairment and dementia. However, whether anxiety is a risk factor for dementia is still not known. We aimed to examine the association between trait anxiety at baseline and the 10-year risk of incident dementia to determine to which extent depressive symptoms influence this relationship in the general population. Methods: Data came from 5,234 community-dwelling participants from the Three-City prospective cohort study, aged 65 years at baseline and followed over 10 years. At baseline, anxiety trait was assessed using the Spielberger State-Trait Anxiety Inventory (STAI), and depressive symptoms using Center for Epidemiologic Studies-Depression Scale (CESD). Use of anxiolytic drugs was also considered. Diagnoses of dementia were made at baseline and every 2 years. To examine the relationship between anxiety exposures and risk of incident dementia, Cox proportional hazard regression models were performed. Results: Taking anxiolytic drugs or having high trait anxiety (STAI score >/= 44) increased the risk of dementia assessed over 10 years of follow-up [Hazard Ratio (HR) = 1.39, 95%CI: 1.08-1.80, p = 0.01 and HR = 1.26, 95%CI: 1.01-1.57, p = 0.04, respectively], independently of a large panel of socio-demographic variables, health behaviors, cardio-metabolic disorders, and additional age-related disorders such as cardiovascular diseases, activity limitations, and cognitive deficit. However, the associations were substantially attenuated after further adjustment for depressive symptoms. Conclusion: Our findings suggest that depressive symptoms shape the association between anxiety trait and dementia. Further research is needed to replicate our findings and extrapolate our results to anxiety disorders

Decreased sAβPPβ, Aβ38, and Aβ40 Cerebrospinal Fluid Levels in Frontotemporal Dementia.

International audienceTo improve the etiological diagnosis of neurodegenerative dementias like Alzheimer's disease (AD) or frontotemporal dementia (FTD), we evaluated the value of individual and combined measurements of the following relevant cerebrospinal fluid (CSF) biomarkers: Tau, 181p-Tau, Aβ38, Aβ40, Aβ42, sAβPPα, and sAβPPβ. This study conducted in two centers included patients with FTD (n = 34), AD (n = 52), as well as a control group of persons without dementia (CTRL, n = 42). Identical clinical criteria and pre-analytical conditions were used while CSF biomarkers were measured using commercial single and multiplex quantitative immunoassays. Thorough statistical analyses, including ROC curves, logistic regressions, and decision trees, were performed. We validated in AD the specific increase of p-Tau levels and the decrease of Aβ42 levels, two biological hallmarks of this disease. Tau concentrations were highest in AD and intermediate in FTD when compared to CTRL. The most interesting results were obtained by focusing on amyloid biomarkers as we found out in FTD a significant decrease of sAβPPβ, Aβ38, and Aβ40 levels. Aβ38 in particular was the most useful biomarker to differentiate FTD subjects from the CTRL population. Combining p-Tau and Aβ38 led us to correctly classifying FTD patients with sensitivity at 85% and specificity at 82%. Significant changes in amyloid biomarkers, particularly for Aβ38, are therefore seen in FTD. This could be quite useful for diagnosis purposes and it might provide additional evidence on the interrelationship between Tau and AβPP biology which understanding is essential to progress towards optimal therapeutic and diagnostic approaches of dementia

Association of long-term diet quality with hippocampal volume: longitudinal cohort study

BACKGROUND: Diet quality is associated with brain aging outcomes. However, few studies have explored in humans the brain structures potentially affected by long-term diet quality. We examined whether cumulative average of Alternative Healthy Eating Index 2010 (AHEI-2010) score during adult life (an 11-year exposure period) is associated with hippocampal volume. METHODS: Analyses were based on 459 participants of the Whitehall Brain Imaging substudy (mean age 59.6[SD=5.3] years in 2002/04, 19.2% women). Multimodal magnetic resonance imaging examination was performed at the end of follow-up (2015-16). Structural images were acquired using a high-resolution 3-dimensional T1-weighted sequence and processed with Functional Magnetic Resonance Imaging of the Brain Software Library (FSL) tools. An automated model-based segmentation/registration tool was applied to extract hippocampal volumes. RESULTS: Higher AHEI-2010 cumulative average score (reflecting long-term healthy diet quality) was associated with a larger total hippocampus volume. For each 1 standard deviation (SD, 8.7 points) increment in AHEI-2010, an increase of 92.5mm3 (SE=42.0mm3) in total hippocampal volume was observed. This association was independent of socio-demographic factors, smoking habits, physical activity, cardio-metabolic health factors, cognitive impairment and depressive symptoms, and was more pronounced in left hippocampus than in right hippocampus . Of the AHEI-2010 components, no or light alcohol consumption was independently associated with larger hippocampus volume. CONCLUSIONS: Higher long-term AHEI-2010 scores were associated with larger hippocampal volumes. Accounting for the importance of hippocampal structures in several neuropsychiatric diseases, our findings reaffirm the need to consider adherence to healthy dietary recommendation in multi-interventional programs to promote healthy brain aging

CSF tau microtubule-binding region identifies pathological changes in primary tauopathies

Despite recent advances in fluid biomarker research in Alzheimer's disease (AD), there are no fluid biomarkers or imaging tracers with utility for diagnosis and/or theragnosis available for other tauopathies. Using immunoprecipitation and mass spectrometry, we show that 4 repeat (4R) isoform-specific tau species from microtubule-binding region (MTBR-tau275 and MTBR-tau282) increase in the brains of corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), frontotemporal lobar degeneration (FTLD)-MAPT and AD but decrease inversely in the cerebrospinal fluid (CSF) of CBD, FTLD-MAPT and AD compared to control and other FTLD-tau (for example, Pick's disease). CSF MTBR-tau measures are reproducible in repeated lumbar punctures and can be used to distinguish CBD from control (receiver operating characteristic area under the curve (AUC) = 0.889) and other FTLD-tau, such as PSP (AUC = 0.886). CSF MTBR-tau275 and MTBR-tau282 may represent the first affirmative biomarkers to aid in the diagnosis of primary tauopathies and facilitate clinical trial designs

Leisure craft sacrificial anodes as a source of zinc and cadmium to saline waters

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Age and the association between apolipoprotein E genotype and Alzheimer disease: A cerebrospinal fluid biomarker-based case-control study

Background: The ε4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association between APOE genotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of β-amyloid peptide (A, β-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. Methods and findings: This case–control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44–96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44–94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least one APOE ε4 allele. Compared with non-ε4 carriers, heterozygous ε4 carriers had a 4.6 (95% confidence interval 4.1–5.2; p < 0.001) and ε4/ε4 homozygotes a 25.4 (20.4–31.2; p < 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (p for interaction < 0.001). The PAF associated with carrying at least one ε4 allele was greatest in the 65–70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect of APOE ε2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD. Conclusions: In this study, we found that AD diagnosis based on biomarkers was associated with APOE ε4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65–70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE ε4 at the population level

Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview

Introduction: The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests. Methods: We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients. Results: The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis. Discussion: This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD