bluuebunny/crossref_metadata_2025_split huggingface dataset:
Usability evaluation of a knowledge graph‐based dementia care intelligent recommender system: A mixed‐methods study
Authors: Leng Minmin 
Published: December 2023

AbstractBackgroundKnowledge graph‐based recommender systems offer the possibility of meeting the personalized needs of people with dementia and their caregivers. However, the usability of such a recommender system remains unknown.ObjectiveThis study aimed to evaluate the usability of a knowledge graph‐based dementia care intelligent recommender system (DCIRS).MethodsA convergent mixed‐methods design was employed to conduct the usability evaluation, including the collection of quantitative and qualitative data. Participants were recruited via social media advertisements. After two weeks of DCIRS use, feedback was collected with the Computer System Usability Questionnaire and semi‐structured interviews. Descriptive statistics were used to describe sociodemographic characteristics and questionnaire scores. Qualitative data were analyzed systematically using inductive thematic analysis.ResultsA total of 56 caregivers were recruited. Quantitative data suggested that the DCIRS was easy for caregivers to use, and the mean questionnaire score was 2.14. Qualitative data showed that caregivers generally believed that the content of the DCIRS was professional, easy to understand, instructive and could meet users’ personalized needs; they were willing to continue to use it. However, the DCIRS also had some shortcomings. Functions that enable interactions between professionals and caregivers and that provide caregiver support and resource recommendations might be added to improve the system’s usability.ConclusionsThe recommender system provides a solution to meet the personalized needs of people with dementia and their caregivers and has the potential to substantially improve health outcomes. The next step will be to optimize and update the recommender system based on caregivers' suggestions and evaluate the effect of the application.
P‐tau217 is the earliest plasma marker of dementia of the Alzheimer’s type in older primary care patients
Authors: Kleineidam Luca , Oezdemir Selçuk , Martino‐Adami Pamela , Weinhold Leonie , Koehler David , Chatterjee Madhurima , Pentzek Michael , Weyerer Siegfried , Bickel Horst , Wiese Birgitt , Riedel‐Heller Steffi G. , Scherer Martin , Blennow Kaj , Zetterberg Henrik , Schmid Matthias , Ruiz Agustin , Peters Oliver , Jeromin Andreas , Wagner Michael , Ramirez Alfredo , Schneider Anja 
Published: December 2023

AbstractBackgroundBlood‐based biomarkers of Alzheimer’s disease (AD) may provide an avenue for early identification of individuals at risk for AD dementia, which is a crucial task for implementing upcoming disease‐modifying therapies in clinical practice. Among blood‐based biomarkers, P‐tau217 has shown a particular sensitivity to amyloid pathology and utility for differential diagnosis of AD. However, less is known about the association of P‐tau217 with dementia risk in older primary care patients.MethodTo address this question in an extreme phenotype design, we measured plasma P‐tau217 using the validated ALZPath pTau217 assay developed on the Single molecule array (Simoa) technology in 184 patients (median age = 83 years) free of dementia at blood draw who converted to clinically diagnosed dementia of the Alzheimer’s type (DAT) during up to eight years of follow‐up. Furthermore, P‐tau217 was measured in 184 age‐ and sex‐matched cognitively normal controls that stayed free of any cognitive impairment during follow‐up. All participants were derived from the primary care‐based AgeCoDe‐cohort. In addition, Aβ42/Aβ40, P‐tau181, NfL, and GFAP were quantified using Simoa technology.Associations between P‐tau217 and conversion to DAT were assessed using conditional logistic regression and compared to associations of conversion to DAT with Aβ42/Aβ40, P‐tau181, NfL, and GFAP. The influence of time to DAT diagnosis on the associations was assessed by generalized additive models.ResultP‐tau217 was strongly associated with conversion to DAT (ORper‐1SD‐increase [95%‐CI] = 10.29 [5.16‐20.41], p = 2.0*10−11, N = 368). This association was present irrespective of whether DAT‐converter showed MCI (ORper‐1SD‐increase [95%‐CI] = 3.49 [1.34‐9.12], p = 1.1*10−2) or no MCI (ORper‐1SD‐increase[95%‐CI] = 16.07[6.54‐39.71], p = 1.3*10−9) at blood draw. No other marker showed a similarly strong association with conversion (second‐best performance: GFAP; ORper‐1SD‐increase [95%‐CI] = 1.36 [1.19‐1.54], p = 2.15*10−2).Patients converting to DAT eight years after blood draw already presented with elevated P‐tau217 levels compared to their matched controls. Other markers (GFAP, P‐tau181) started to show differences in individuals converting to DAT four years after blood draw.ConclusionP‐tau217 is the most sensitive plasma marker for risk of conversion to DAT in older patients from primary care patients in comparison to plasma P‐tau181, Aβ42/Aβ40, NfL, and GFAP.
The involvement of GLP1 signaling with the effect of oral galactose in the hypothalamus of sporadic Alzheimer’s disease rat model
Authors: Knezovic Ana , Barilar Jelena Osmanovic , Homolak Jan , Perhoc Ana Babic , Salkovic‐Petrisic Melita 
Published: December 2023

AbstractBackgroundIntracerebroventricular (icv) application of streptozotocin (STZ) causes mytochondrial dysfunction, oxidative stress and other metabolic effects, which leads to accumulation of τ‐protein and Aß plaques that makes it suitable for animal model of sporadic Alzheimer’s disease (sAD). We aimed to explore whether acute effect of single oral galactose dose is mediated by glucagon‐like peptide‐1 (GLP‐1) in sAD rat model.MethodWistar rats were injected icv with STZ (3 mg/kg) or vehicle only (CTR). One month after the injection, animals were divided into three experiments. First experiment: 200 mg/kg galactose was given orally and CTR animals were sacrificed 30, 60 and 120 min after administration. Second experiment: GLP‐1R antagonist (Exendin 9‐39, 85 µg/kg; GLP1Ra) was administered icv in both groups and animals were sacrificed 30 min after the injection. Third experiment: 30 min prior to oral galactose, rats were injected icv with GLP‐1Ra, and animals were sacrificed 120 min after galactose load. PDH, COXIV, CytC and Casp‐3 levels were measured by Western blot method and lactate, ATP and SOD were measured by ELISA in HPT. Glucose, galactose and GLP‐1 levels were measured in plasma and CSF. Data were analyzed by principal component analysis and Spearman rank correlation.ResultMetabolic changes were found more pronounced 120 min after single galactose load: reduced levels of Casp‐3 and PDH and increased SOD levels in HPT; increased CSF glucose. GLP1Ra decreased the levels of lactate, COXIV and CytC and increased PDH and Casp‐3 levels in HPT, only in STZ treated animals. CytC was found negatively correlated with ATP and PDH levels in HPT. GLP1Ra decreased the levels of CytC and SOD and increased PDH levels in CTR only after oral galactose.ConclusionGLP1Ra might inhibit decreased PDH levels caused by single galactose load. GLP1R central inhibition has more pronounced effect in STZ‐icv treated rats suggesting the involvement of GLP1 signaling in model pathogenesis.
Supported by Croatian Science Foundation and co‐financed by the Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience (project “Experimental and clinical research of hypoxic‐ischemic damage in perinatal and adult brain”; GA KK01.1.1.01.0007 funded by the European Union through the European Regional Development Fund).
Clinical proteomic analysis across the Alzheimer’s disease continuum
Authors: Weiner Sophia , Sauer Mathias , Ashton Nicholas J. , Benedet Andrea Lessa , Rosa‐Neto Pedro , Blennow Kaj , Zetterberg Henrik , Gobom Johan 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD), defined by amyloid‐β (Aβ) and neurofibrillary tau tangles, can be viewed as a continuum, starting with an asymptomatic “pre‐clinical” phase that progresses to a symptomatic clinical stage characterized as mild cognitive impairment (MCI), and finally, AD dementia. Identifying biomarkers reflective of the different disease stages is important to detect individuals at risk of developing AD, to monitor disease progression and the effect of treatments, as well as to determine new therapeutic targets.MethodWe present data from a cross‐sectional tandem mass tag (TMT) proteomic study of cerebrospinal fluid (CSF) samples from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort (young adults (n = 22), cognitively unimpaired (n = 54), cognitively impaired (n = 26), MCI (n = 19), AD (n = 19), non‐AD (n = 16), frontotemporal dementia (n = 9); total n = 214); a highly profiled cohort across the AD continuum with clinical and neuropsychological assessments, MRI, and Aβ and tau positron emission tomography (PET). To enhance detection of brain‐derived proteins, we evaluated the use of a TMT booster channel consisting of brain protein extract. Planned statistical analyses include linear regression modelling to compare biomarker distributions across groups, covariating for sex and age where appropriate as well as correlation analyses of biomarker levels with Aβ and tau PET measurements.ResultOur preliminary data analysis suggests that a set of proteins differed with high significance between amyloid PET negative and positive individuals (Fig. 1), including proteins that showed changes already at the pre‐clinical stage of AD. We will explore the correlation of the identified biomarker candidates with pathological process and disease progression, as well as with Aβ‐ and tau‐PET measurements. Also, protein changes associated with aging and other neurodegenerative disorders will be evaluated. Finally, the use of a TMT booster based on brain protein extract to enhance identification of CSF biomarkers will be assessed.ConclusionThis study describes the most extensive unbiased proteomic profiling in CSF across the AD continuum, identifying proteins that may serve as novel therapeutic targets and fluid biomarkers for the disease. Additionally, the use of a TMT booster to enhance the detection of brain‐derived proteins was evaluated.
The ABOARD Cohort Panel: public involvement in a Dutch Cohort study on a personalized medicine approach for Alzheimer’s disease
Authors: de Rijke Tanja J. , Smeitink Marlon , Beusink Miriam , Van der Rhee Els , Saaltink Dirk‐Jan , van der Landen Sophie M. , Smets Ellen M.A. , Handgraaf Dédé , de Boer Casper , Meester Hanneke F.M. Rhodius‐ , Schaaij‐Visser Tieneke B.M. , van der Flier Wiesje M. , Visser Leonie N.C. 
Published: December 2023

AbstractBackgroundABOARD is a Dutch public‐private partnership aiming for a personalized medicine approach for Alzheimer’s disease. Within this project, the ABOARD Cohort is initiated: a national prospective data infrastructure with the objective to study the AD disease trajectory using PROMS and linked clinical data. The ABOARD Cohort Panel has been installed to provide advice on the design, execution, and direction of the study. By incorporating the perspective of potential participants the meaningfulness and accessibility of the ABOARD Cohort is ensured.MethodRecruitment for the panel has been initiated by the Dutch Brain Foundation via social media and newsletters, and approximately 300 people responded with potential interest. To further inform them, we hosted a webinar explaining the ABOARD Cohort Panel. Hereafter, respondents received an official Panel invitation and initial survey (including principles for collaboration), resulting in 59 people signing up as panellists.ResultPanel members are on average 62 years old, 78% is female, 96% has no migration background, and 52% participated in a panel before. Panellists vary in education level and geographic distribution. The majority has a personal interest in dementia (64%) and/or friends/family with dementia (62%). When asked how they would like to be involved, they indicated wanting to be involved in online questionnaires (100%), online focus groups (56%), and in‐person focus groups (36%). The majority preferred monthly questionnaires (50%) with a duration of 10‐20 minutes (52%). In the first months, panellists provided feedback in online surveys on the ABOARD Cohort information letter and informed consent form. They considered these lengthy, too difficult, and raising questions. An in‐depth live session was held with panellists to test subsequent adjustments, resulting in higher agreement rates on the informed consent procedure of the ABOARD Cohort. Panellists also advised on the communication strategy of the national ABOARD Cohort campaign, which is currently being implemented. In the coming months, panel members will test the usability of the ABOARD Cohort portal and an online cognitive test and advice on dissemination and variables that are being collected.ConclusionThe ABOARD Cohort Panel incorporates the perspective of potential participants and aims to ensure the meaningfulness and accessibility of the ABOARD Cohort.
Chromosome Y‐haplotype mediates cognitive resilience and differential expression of transposable elements in 5xFAD‐carrying AD‐BXD males
Authors: Boas Stephanie M. , Saul Michael C. , Anderson David , Philip Vivek M. , Ramirez Paulino , Frost Bess , Beck Christine R. , Kaczorowski Catherine C. 
Published: December 2023

AbstractBackgroundIn Alzheimer’s disease (AD), risk factors and clinical progression differ between sexes. Men have lower post‐diagnosis life‐expectancies 1,2, while women display worsened cognitive decline than men with similar neuropathology3‐5 or shared genetic risk6,7. Investigation of sex‐specific genetic contributions to AD has largely focused on the X‐chromosome, but emerging evidence has also linked somatic Y‐chromosomal instability to age‐linked disease outcomes, including AD8‐10. Notably, the Y‐chromosome contains few coding genes, but is enriched with transposable elements (TEs)11, enigmatic DNA sequences capable of introducing variation into the genome12. Differential expression of TEs has recently been reported in AD13‐15. We hypothesize that TEs could contribute to sex‐specific variation observed in AD onset and progression.MethodHere, we utilized bulk hippocampal RNAseq and contextual fear memory (CFM) data from a 28‐strain AD‐BXD dataset comprised of male and female 5xFAD‐carrying animals and non‐transgenic (Ntg) littermates to investigate whether expression of coding genes and/or TEs contribute to AD‐relevant sex differences and cognitive outcomes. Data were stratified by sex and Y‐chromosome haplotype (C57BL/6J‐type vs. DBA/2J‐type). TEs were quantified in RNAseq data using TETranscripts16. For each TE, we predicted genomic localization using DFAM17, and calculated sex‐specific heritability.ResultIn 5xFAD animals, C57BL/6J‐type males significantly out‐performed both DBA/2J‐type males and females on a CFM task (Fig.1). TEs identified in this dataset were differentially expressed due to both sex and Y‐chromosome haplotype in 5xFAD animals (Fig.2). Interestingly, Y‐haplotype did not affect Y‐chromosome coding gene expression. We calculated that a large portion of TEs identified in our dataset are highly heritable, with differential heritability associated with sex and 5xFAD‐transgene status (Fig.3)ConclusionWe report that the C57BL/6J Y‐chromosome confers cognitive resilience in 5xFAD males, which may undermine the utility of models maintained on a homogenous C57BL/6J background as tools for investigating age‐related cognitive decline. We speculate that differential TE expression/activity between Y‐haplotypes and between sexes may account for differential resilience, but further investigation is needed to establish this link directly. Finally, our data suggest that not only are TEs likely influencers of AD risk and disease progression, but that TE expression in disease states may be heritable, rather than stochastically induced.
Concordance between APOE genotyping and proteotyping using the novel Lumipulse G Pan‐ApoE and Lumipulse G ApoE4 RUO assays
Authors: Degrieck Rosina , Denoyette Mario , Delanote Jarne , De Jonge Maarten , Umeda Kazuyuki , Yuri Tatsushi , Umeda Dagmara Minczakiewicz , Bastard Nathalie Le , Sato Hideo , Nojima Hisashi , Aoyagi Katsumi , Vandenbroucke Ina 
Published: December 2023

AbstractBackgroundThe APOE gene has three different alleles that encode for three different ApoE protein isoforms (APOE2, APOE3, and APOE4), resulting in 6 different phenotypes. Nucleic acid amplification test remains the gold standard for APOE genotyping, however quantification of the ApoE proteins using immunoassays could provide another piece of information, related to the expression levels of the proteins. In this regard, ApoE as a protein biomarker can be used in research to determine its value alone or as part of a panel of plasma biomarkers.MethodThe LUMIPULSE G System is a chemiluminescent enzyme immunoassay platform enabling fully automated processing of samples using ready‐to‐use immunoreaction cartridges. Time to result in these single use test cartridges takes about 30 minutes. The analytical performance of the newly developed Lumipulse G Pan‐ApoE and Lumipulse G ApoE4 RUO assays was determined. Parameters analyzed were precision, sensitivity, linearity, prozone and potential impact of interfering substances. Proof of concept of these novel assays was verified with a set of 230 genotyped plasma samples.ResultThe total within‐lab variability of both assays was ≤8% CV confirming high precision of the LUMIPULSE G system. Using low ApoE concentrated plasma samples, the observed LoD and LoQ (@20% CV) was 0.072 µg/mL (Pan‐ApoE) and 0.152 µg/mL (ApoE4). Linearity was shown across the assay range (0 – 100 µg/mL) for both assays. Neither prozone effect nor significant impact (recovery within 100±10%) of commonly tested endogenous substances (bilirubin, haemoglobin, low and high Protein content, and human anti‐mouse antibodies (HAMA)) was observed. Potential interference was observed for triglycerides and rheumatoid factor (RF) with observed recovery within 100±20%. ApoE proteotyping based on the novel assays resulted in a 99.8% concordance with APOE genotyping (1 discordant result). Moreover, applying the ratio ApoE4/Pan‐ApoE with the measurement values of respective assays, classified correctly between hetero‐ and homozygous E4 carrier status.ConclusionThe analytical performance studies demonstrate low variability and high sensitivity enabling measurement of pan‐ApoE and ApoE4 in plasma. Pan‐apoE and apoE4 quantification can offer relevant insights into the assessment of subjects at risk for AD or adverse events following anti‐amyloid treatments and should be studied further.
Correlations of p‐tau217, p‐tau181 and tau levels between CSF and plasma that are measured by fully automated immunoassay platform
Authors: Matsumoto Kazuya , Murakami Shun , Mori Asuka , Arai Nari , Ishiki Kengo , Gupta Ishita , Watanabe Shunsuke , Yamashita Kazuto , Ishimoto Tadashi , Kurosaki Masae , Miura Masahiro , Iwanaga Shigeki , Sato Toshiyuki 
Published: December 2023

AbstractBackgroundCerebrospinal fluid (CSF)‐based ATN classification (A: β‐amyloid (Aβ) deposition, T: pathogenic tau accumulation, N: neurodegeneration) is being widely accepted for the characterization of Alzheimer’s disease (AD). However, for the implementation of ATN classification in clinical practice, blood‐based biomarker is preferable in terms of specimen collection ease. Therefore, we have developed the blood‐based biomarker assays that correlate well with CSF levels. We have previously demonstrated that the plasma tau and phosphorylated tau at threonine‐181 (p‐tau181) immunoassays can significantly differentiate between AD, mild cognitive impairment (MCI), and cognitively normal (CN) groups. Here, we evaluated the correlation of biomarker levels between CSF and plasma utilizing the biomarker panel with addition of phosphorylated tau at threonine‐217 (p‐tau217) immunoassay.MethodWe have measured p‐tau217, p‐tau181 and tau using commercially available specimens on a fully automated immunoassay platform, HISCLTM analyzer. The platform can achieve high degree of sensitivity, requires only 30 µl of sample and 17 minutes to complete the measurement per assay. The bio‐analytical performance for the immunoassays was evaluated by measuring lower limit of quantification (LLOQ). The developed immunoassays were used to measure the paired CSF and plasma specimens from AD (n = 10), MCI (n = 35) and CN (n = 9) groups.ResultThe quantitative sensitivity for p‐tau217, p‐tau181 and tau were sufficient to measure plasma specimens in all groups. The plasma biomarker levels were significantly different between the AD and CN groups for all the biomarkers. We have found good correlations of biomarker levels between CSF and plasma for p‐tau217 (rs = 0.594, p < 0.01), p‐tau181 (rs = 0.453, p < 0.01) and tau (rs = 0.326, p < 0.05).ConclusionOur results indicated the possibility of detecting plasma p‐tau217, p‐tau181 and tau levels which may reflect the CSF levels. In addition to these assays, we have also developed plasma Ab and neurofilament light chain assays that had demonstrated good correlation with CSF levels. Thus, all the plasma assays developed on the HISCL analyzer could assess ATN classification. The blood‐based biomarker panel using our fully automated assay will accelerate research in the dementia field and may help in appropriate diagnosis of patients with dementia in routine clinical practice.
Associations of 24‐h rest‐activity patterns with plasma markers of neurodegeneration and Alzheimer’s disease pathology in cognitively unimpaired individuals
Authors: Van Egroo Maxime , Beckers Elise , Ashton Nicholas J. , Blennow Kaj , Zetterberg Henrik , Jacobs Heidi I.L. 
Published: December 2023

AbstractBackgroundAltered 24‐h rest‐activity rhythms have been previously associated with higher burden of Alzheimer’s disease (AD) pathological hallmarks, as measured with positron emission tomography or cerebrospinal fluid collection. Recent developments in fluid biomarkers now allow to non‐invasively measure levels of AD‐related pathology in the plasma. Here, we examined whether actigraphy‐derived 24‐h rest‐activity patterns could be linked to plasma markers of neurodegeneration and AD pathology in a sample of cognitively unimpaired participants.MethodNinety‐three asymptomatic individuals (mean age = 59.73 ± 13.74 y., range = 30 – 85 y., 48 females, Table 1) underwent 10 days of actigraphic recordings, and blood drawing. Standard non‐parametric indices of 24‐h rest‐activity rhythm fragmentation (intradaily variability, IV) and stability (interdaily stability, IS) were extracted using the GGIR package (v2.8‐2) in R. Plasma concentrations of neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), 40 and 42 amino acid‐long amyloid‐β (Aβ40 and Aβ42, respectively), total tau, and phosphorylated tau at threonine 181 (pTau181) or threonine 231 (pTau231) were measured using Single molecule array technology.ResultMultiple linear regression models adjusted for age, sex, education, and body mass index, showed that worse rest‐activity rhythm fragmentation, as indicated by higher IV values, was strongly associated with elevated levels of plasma NfL (t = 4.53, p < .0001, Figure 1), but also with higher levels of plasma GFAP (t = 2.44, p = .02, Figure 2) and lower plasma Aβ42/40 ratio (t = ‐2.23, p = .03, Figure 2). Similarly, increased day‐to‐day rest‐activity rhythm stability, as indicated by higher IS values, was associated with lower levels of plasma NfL (t = ‐2.37, p = .02, Figure 1). By contrast, no significant relationships were found between IV or IS values and total tau or phosphorylated tau plasma biomarkers (all p > .27).ConclusionThese findings provide further evidence that disrupted rest‐activity patterns, in particular fragmentation of rest‐activity rhythms, may constitute a sensitive marker of incipient AD pathology and neurodegeneration in cognitively unimpaired individuals. Our study therefore highlights the clinical utility of monitoring rest‐activity patterns for improved detection of individuals at‐risk for neurodegenerative diseases, including AD.