1,721,277 research outputs found
Multimorbidity patterns and blood biomarkers of Alzheimer's disease in community-dwelling cognitively unimpaired older adults
No full textINTRODUCTION: Alzheimer's disease (AD) blood biomarkers hold clinical potential but their concentration may vary with somatic conditions. METHODS: We investigated the concentration of six AD blood biomarkers in relation to multimorbidity as disease count and four multimorbidity patterns in 2290 cognitively unimpaired older adults. RESULTS: Levels of phosphorylated tau (p-tau)181, p-tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) increased with increasing number of diseases. In multi-adjusted regressions, compared to individuals without multimorbidity, the anemia/sensory impairment pattern was associated with altered levels of all biomarkers except amyloid beta (Aβ)42/40, GFAP, and total tau (p-tau181: β = 0.18, 95% confidence interval [CI]: 0.08, 0.28; p-tau217: β = 0.11, 95% CI: 0.03, 0.18; NfL: β = 0.14, 95% CI: 0.06, 0.21) and the cardiometabolic/inflammatory pattern was associated with altered levels of all biomarkers except Aβ42/40 and GFAP (p-tau181: β = 0.24, 95% CI: 0.12, 0.36; p-tau217: β = 0.23, 95% CI: 0.14, 0.32; NfL: β = 0.32, 95% CI: 0.23, 0.40; total tau: β = 0.23, 95% CI: 0.07, 0.39). Results remained unchanged after excluding those who developed dementia in 15 years. DISCUSSION: More diseases and specific multimorbidity patterns altered the levels of several AD blood biomarkers, highlighting caution when using them in adults with complex health profiles. Highlights: In cognitively unimpaired older adults blood biomarkers of Alzheimer's disease varied depending on the number of chronic diseases and specific patterns of multimorbidity. Phosphorylated tau (p-tau)181, p-tau217, neurofilament light chain (NfL), and glial fibrillary acidic protein levels increased along with increasing numbers of chronic diseases. P-tau181, p-tau217, and NfL levels were significantly higher in individuals in the anemia/sensory impairment and cardiometabolic/inflammatory multimorbidity patterns compared to those without multimorbidity. Results remained unchanged after excluding participants who developed dementia during 15-year follow-up
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Evidence for the derivation of a peptide ligand from the amyloid β-protein precursor of Alzheimer's disease
No full textA monoclonal antibody to a synthetic peptide consisting of residues 8-17 of amyloid beta-protein was used in immunohistochemical studies to reveal binding sites for this peptide in cytoplasmic vesicles in cells of the adrenal zona reticularis and the islets of Langerhans of the pancreas. These binding sites showed some specificity for this peptide and so may represent a membrane receptor. These results suggest that the membrane bound beta-protein precursor may be processed by limited extracellular proteolysis to release a peptide ligand containing the 8-17 sequence. It has been reported recently that the core protein of a heparin sulphate proteoglycan (HSPG) secreted by PC12 cells shows some homology with the beta-protein precursor. This suggests that the binding sites might be due to the presence of a HSPG core protein receptor. Further studies should be carried out to find out if receptors to beta-protein peptides are present in brain tissue, since these might play a role in the catabolism of the beta-protein precursor, and in the formation of cerebral amyloid in Alzheimer's disease (AD)
Phosphorylation of protein tau and rescue of protein tau-induced axonopathy by GSK-3 beta in GSK-3 beta xhtau40 double transgenic mice
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A Genomic Search for Alzheimer's Disease Genes
No full textAlzheimer's disease is the leading cause of dementia in the elderly and the most common form of dementia occurring after the age of 40. Alzheimer's disease has a complex genetic etiology with a strong genetic component that likely involves both gene–gene and gene–environment interactions.
We have identified 16 potential genomic regions of interest in theses data using a genomic screening strategy of our large (n=466) family dataset.
Approaches such as those we have used here, together with new statistical methodologies such as conditional linkage analysis, generalized family‐based association tests such as the Pedigree Disequilibrium Test, and the use of new molecular technologies such as single nucleotide repeat polymorphisms, open the door for additional Alzheimer's disease gene discovery
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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