Plasma phosphorylated-tau181 as a predictive biomarker for Alzheimer’s amyloid, tau and FDG PET status

Plasma phosphorylated-tau181 (p-tau181) showed the potential for Alzheimer’s diagnosis and prognosis, but its role in detecting cerebral pathologies is unclear. We aimed to evaluate whether it could serve as a marker for Alzheimer’s pathology in the brain. A total of 1189 participants with plasma p-tau181 and PET data of amyloid, tau or FDG PET were included from ADNI. Cross-sectional relationships of plasma p-tau181 with PET biomarkers were tested. Longitudinally, we further investigated whether different p-tau181 levels at baseline predicted different progression of Alzheimer’s pathological changes in the brain. We found plasma p-tau181 significantly correlated with brain amyloid (Spearman ρ = 0.45, P 18.85 pg/ml) at baseline had a higher risk of pathological progression in brain amyloid (HR: 2.32, 95%CI 1.32–4.08) and FDG PET (3.21, 95%CI 2.06–5.01) status. Plasma p-tau181 may be a sensitive screening test for detecting brain pathologies, and serve as a predictive biomarker for Alzheimer’s pathophysiology

Quality indicators of nutritional care practice in elderly care

Objectives: The aim is to explore the effects of antecedent, structural and process quality indicators of nutritional care practice on meal satisfaction and screened nutritional status among older adults in residential care homes. Design: Data for this Swedish cross-sectional study regarding older adults living in residential care homes were collected by i) a national questionnaire, ii) records from the quality registry Senior Alert, iii) data from an Open Comparison survey of elderly care in 2013/2014. The data represented 1154 individuals in 117 of 290 Swedish municipalities. Measurements: Meal satisfaction (%) and adequate nutritional status, screened by the Mini Nutritional Assessment Short Form (MNA-SF), were the two outcome variables assessed through their association with population density of municipalities and residents' age, together with 12 quality indicators pertaining to structure and process domains in the Donabedian model of care. Results: Meal satisfaction was associated with rural and urban municipalities, with the structure quality indicators: local food policies, private meal providers, on-site cooking, availability of clinical/community dietitians, food service dietitians, and with the process quality indicators: meal choice, satisfaction surveys, and 'meal councils'. Adequate nutritional status was positively associated with availability of clinical/community dietitians, and energy and nutrient calculated menus, and negatively associated with chilled food production systems. Conclusion: Municipality characteristics and structure quality indicators had the strongest associations with meal satisfaction, and quality indicators with local characteristics emerge as important for meal satisfaction. Nutritional competence appears vital for residents to be well-nourished

The use of small Bloodstains in Blood Source Area of Origin Determinations

Due to the increased likelihood of manual measurement error, small bloodstains (≤ 3.0mm long) have rarely been used in three-dimensional blood source area of origin determinations. The advent of computer assisted measurement methods, offering improved levels of accuracy and precision, broadens the range of bloodstain sizes available for selection to determine a blood source area of origin. With inertia, viscosity and surface tension playing important, yet competing, roles in bloodstain formation, the power law relationships that exist between droplet volumes, droplet diameter, and bloodstain width suggest possible non-agreement between experimentally calculated angle of impact values when compared against those values theoretically expected. In order to compare experimental angle of impact calculation trends with angle of impact calculation theory, this preliminary study examines small bloodstains created by blood drops falling vertically onto surfaces offset from the vertical and small bloodstains generated by impact events subsequently deposited on adjacent vertical surfaces. This study shows that an apparent power law relationship may exist between the size of a parent blood droplet and the role of viscous and surface tension forces on subsequent bloodstain formation, particularly on those bloodstains caused by small droplets impacting obliquely with planar surfaces

The Polygenic Risk Score Knowledge Base offers a centralized online repository for calculating and contextualizing polygenic risk scores

The process of identifying suitable genome-wide association (GWA) studies and formatting the data to calculate multiple polygenic risk scores on a single genome can be laborious. Here, we present a centralized polygenic risk score calculator currently containing over 250,000 genetic variant associations from the NHGRI-EBI GWAS Catalog for users to easily calculate sample-specific polygenic risk scores with comparable results to other available tools. Polygenic risk scores are calculated either online through the Polygenic Risk Score Knowledge Base (PRSKB; https://prs.byu.edu ) or via a command-line interface. We report study-specific polygenic risk scores across the UK Biobank, 1000 Genomes, and the Alzheimer's Disease Neuroimaging Initiative (ADNI), contextualize computed scores, and identify potentially confounding genetic risk factors in ADNI. We introduce a streamlined analysis tool and web interface to calculate and contextualize polygenic risk scores across various studies, which we anticipate will facilitate a wider adaptation of polygenic risk scores in future disease research

Genetic associations with dementia‐related proteinopathy: Application of item response theory

IntroductionAlthough dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete.MethodsWe applied multidimensional generalized partial credit modeling (GPCM) to test genetic associations with dementia-related proteinopathies. Data were analyzed to identify candidate single nucleotide variants for the following proteinopathies: Aβ, tau, α-synuclein, and TDP-43.ResultsFinal included data comprised 966 participants with neuropathologic and WGS data. Three continuous latent outcomes were constructed, corresponding to TDP-43-, Aβ/Tau-, and α-synuclein-related neuropathology endophenotype scores. This approach helped validate known genotype/phenotype associations: for example, TMEM106B and GRN were risk alleles for TDP-43 pathology; and GBA for α-synuclein/Lewy bodies. Novel suggestive proteinopathy-linked alleles were also discovered, including several (SDHAF1, TMEM68, and ARHGEF28) with colocalization analyses and/or high degrees of biologic credibility.DiscussionA novel methodology using GPCM enabled insights into gene candidates for driving misfolded proteinopathies.HighlightsLatent factor scores for proteinopathies were estimated using a generalized partial credit model. The three latent continuous scores corresponded well with proteinopathy severity. Novel genes associated with proteinopathies were identified. Several genes had high degrees of biologic credibility for dementia risk factors