bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rational Design of Platinum–Bismuth Sulfide Schottky Heterostructure for Sonocatalysis‐Mediated Hydrogen Therapy
Authors: Yuan Meng , Liang Shuang , Yang Ling , Li Fang , Liu Bin , Yang Chunzheng , Yang Zhuang , Bian Yulong , Ma Ping'an , Cheng Ziyong , Lin Jun 
Published: December 2022

AbstractConventional sonodynamic therapy is unavoidably limited by the tumor microenvironment, although many sonosensitizers have been developed to improve them to a certain extent. Given this, a concept of sonocatalytic hydrogen evolution is proposed, which is defined as an oxygen‐independent therapeutics. To demonstrate the feasibility of the concept, the narrow‐bandgap semiconductor bismuth sulfide (Bi2S3) is selected as the sonocatalyst and platinum (Pt) nanoparticles are grown in situ to optimize their catalytic performance. In this nanocatalytic system, the Pt nanoparticles help to capture sonoexcited electrons, whereas intratumoral overexpressed glutathione (GSH), as a natural hole sacrificial agent, can consume sonoexcited holes, which greatly improves the charge‐separation efficiency and promotes controllable and sustainable H2 generation. Even under hypoxic conditions, the Pt‐Bi2S3 nanoparticles can also produce sufficient H2 under ultrasound irradiation. Mechanistically, mitochondrial dysfunction caused by H2 and intratumoral redox homeostasis destruction by GSH depletion synergistically damage DNA to induce tumor cells apoptosis. At the same time, the Pt nanoparticles and holes can also trigger the decomposition of hydrogen peroxide into O2 to relieve tumor hypoxia, thus being synergistic with GSH depletion to reverse tumor immunosuppressive microenvironment. The proposed sonocatalysis‐mediated therapy will provide a new direction to realize facile and efficient cancer therapy.
Multimodal, scalable and affordable neurocognitive biomarkers
Authors: Parra‐Rodriguez Mario A ,   The Geroscience Center for Brain Health and Metabolism (GERO), Chile and the Neuroscience Group, University of Antioquia, Colombia
Published: December 2022

AbstractBackgroundAlzheimer’s disease (AD) biomarkers targeting Aβ, Tau, and Neurodegeneration are creating unprecedented opportunities for its early detection. Adhering to the A/T/N biomarker framework though comes with several challenges, mainly due to high costs. The Joint Program for Neurodegenerative Diseases (JPND) suggested that efforts should also be directed to harmonise promising cognitive tests. The group recommended the Short‐Term Memory Binding (STMB) and Selective Reminding Tests (SRT). To that aim, we need to explore if such memory markers hold differential sensitivity to the AD continuum (Aim1). Whether such deficits are observable in preclinical and prodromal stages of AD regardless of the disease variants (sporadic and familial) is also unclear (Aim2). Moreover, whether combining these cognitive makers with EEG and Eye‐Tracking (ET) would yield neurocognitive biomarkers for AD (Aim3) needs further research.MethodsMemory tests recommended by the JPND and standard neuropsychological assessments entered harmonised research protocols supporting three large international collaborations. Aim1: Project 1 (UK based) involved 150 participants (HC=70, MCI=80) and Project 2, ran in collaboration with GERO, Chile, involved 264 participants (HC=37, SCC=117, MCI=79, ADD=31). Aim2: Project 3: ran in collaboration with the Neuroscience Group, University of Antioquia, Colombia involved 334 participants (HC=210, AC=124). Aim3: The STMBT combined with EEG was recorded from 20 participants and combined with Eye‐tracking from 71 participants all from Project 3.ResultsAim1: STMB deficits are detectable from the very early stages of AD (HC>SCC>(MCI=ADD)) before associative memory deficits (SRT) become apparent ((HC=SCC)>MCI>ADD). Aim2: Such deficits are also prominent in AC when their associative memory abilities remain intact. Aim3: When combined with EEG, STMB differentiated AC from HC with 89% accuracy while with ET classification accuracy reached 98%.ConclusionThe collaborative efforts here presented suggest that AD can be detected with appropriate, affordable, culture‐free and scalable neurocognitive biomarkers recently recommended by the JPND before clinical manifestations of the disease become apparent.GlossaryAC = Asymptomatic Carriers of the mutation E280A‐PSEN1; ADD = Alzheimer’s disease Dementia; GERO = The Geroscience Center for Brain Health and Metabolism; HC = Healthy Controls; MCI = Mild Cognitive Impairment; SCC = Subjective Cognitive Complaint; STMBT: Short‐Term Memory Binding Test.
Using social media marketing to increase diversity in Alzheimer’s clinical trial participation
Authors: Starling Sarah J , Harber Steven J , Munoz Gabriella S , Thorpe Daniel T , Engler Jenicka M , Evans Miriam M , Sutton James P 
Published: December 2022

AbstractBackgroundAlzheimer’s Disease (AD) clinical trials often lack diversity in study participants. Older Black adults are nearly twice as likely as their White peers to have Alzheimer’s disease or other dementias, but are underrepresented in AD clinical trials. Social media recruitment may help improve diversity in AD clinical trials.MethodsRecruitment data from Facebook advertisements and physician referrals for anti‐amyloid clinical trials at a Boston‐based research site between April and December 2021 were examined. 2,838 potential participants contacted the site through Facebook advertisements, of which 476 completed a phone screen interview with a recruiter. Of the 143 participants who passed the phone screen and attended an in‐person prescreening visit with a clinician, 69 screened for an industry‐sponsored clinical trial. Referrals from local neurologists resulted in 19 participants attending prescreening, 13 eventually screening for a trial. Demographics for participants were compared to census data for the Boston Metropolitan Area.ResultsOf the 143 participants recruited from Facebook who completed a prescreening visit, 87.4% identified as White, 9.8% as Black, and 2.8% as Asian or other. 3.5% were White Hispanic and 2.1% were Non‐White Hispanic. 100% of physician referrals identified as White, non‐Hispanic. The Facebook‐recruited sample was stratified into three age groups: 55‐64, 65‐74, and 75‐86. All age groups recruited from Facebook had an equal or higher percentage of Black participants than would be expected based on census data. While 6.5% of the local age 55‐64 population are Black, 13% of Facebook‐recruited participants in that age group identified as Black. Similarly, while 5.5% of the age 65‐74 population are Black, 12.3% of Facebook‐recruited participants in that age group identified as Black. Finally, 5.5% of the oldest cohort (75+) of Facebook‐recruited participants identified as Black, closely matching census data for that age group (5.2%).ConclusionSocial media advertising may be an effective way to recruit a more diverse population of participants for AD clinical trials. In this sample, Facebook recruitment overrepresented some minority groups, which is meaningful given the prevalence of dementia in Black adults. Expanding study recruitment tactics represents an important step towards clinical trial populations that more accurately represents the real‐world AD patient population.
Effect of Neuroinflammation on white matter structure and memory performance in the spectrum from aging to AD
Authors: Hayek Dayana , Ziegler Gabriel , Kleineidam Luca , Brosseron Frederic , Vockert Niklas , Buerger Katharina , Fliessbach Klaus , Laske Christoph , Peters Oliver , Priller Josef , Ramirez Alfredo , Schneider Anja , Spottke Annika , Teipel Stefan , Wiltfang Jens , Wolfsgruber Steffen , Yakupov Renat , Jessen Frank , Duzel Emrah , Wagner Michael , Heneka Michael T. , Maass Anne ,   DELCODE study group
Published: December 2022

AbstractBackgroundNeuroinflammation is a hallmark of Alzheimer ́s disease (AD) and other neurodegenerative disorders and is likely to be triggered throughout different stages of the disease. Microglia and Astrocytes are the main resident glia that mediate neuroinflammation through production of cytokines, chemokines and other neuroinflammatory biomarkers. Inflammatory processes have been implicated in the pathogenesis of cerebrovascular disease and white matter (WM) injury. However, imaging studies on the contribution of inflammation on WM structure in the aging and AD are rare.MethodHere, we aim to examine the relationship between inflammatory markers and WM hyperintensities (WMH) in the spectrum from normal aging towards AD. To do that, we used baseline data from the DZNE DELCODE study that is enriched in subjects at risk for development of AD and examined a panel of 16 inflammatory biomarkers from CSF of 249 subjects who also underwent FLAIR imaging. Participants included cognitively unimpaired (CU) individuals (healthy controls, AD relatives, and SCD) and cognitively impaired patients (CI) with MCI or AD dementia. WMH lesion volumes were automatically segmented from FLAIR images. Principal component analysis on the CSF markers generated one main composite factor (CP1) that included mainly TREM2, YKL40, AXL, Tyro3 and C1q (see Figure). Age, sex, vascular risk factors, Abeta ratio and ptau181 were used as covariates.ResultLinear regression models showed that higher values of this inflammatory composite factor was related to lower global WMH (p<0.01) and better memory performance (p<0.01) in the whole sample. These effects were also significant when including whole brain GM volume as additional covariate. Mediation model showed that global WMH partially mediated the effect of neuroinflammation on memory performance.ConclusionThese results suggest that some neuroinflammatory markers (e.g. sTyro3 and sAXL) might have a protective effect on WM structure, thus being beneficial for memory function as suggested by a recent study (Brosseron, Maass, Kleineidam et al, 2022), in which sTyro3 and sAXL were related to higher GM volume. Follow‐up analyses will aim to distinguish the effect of neuroinflammation in different clinical groups. Longitudinal studies are ultimately needed to determine whether the observed effect is “protective” or related to “brain reserve”.
The role of IGFBP2 in pre‐symptomatic Alzheimer's disease: a multimodal longitudinal study of cognitively unaffected individuals with a family history of sporadic Alzheimer’s disease
Authors: Quesnel Marc James , Labonté Anne , Picard Cynthia , Rosa‐Neto Pedro , Villeneuve Sylvia , Poirier Judes ,   PREVENT‐AD Research Group
Published: December 2022

AbstractBackgroundInsulin‐like growth factors (IGF) play pivotal roles in neurogenesis, neuronal survival, synaptogenesis and compensatory repair mechanisms following injury. Insulin‐like growth factor binding proteins (IGFBP) bind to IGFs, and regulate interactions between IGFs and their cell surface receptors. In the brain, IGFBP2 is the most abundant IGFBP. Several studies have observed altered IGFBP2 levels in Alzheimer’s disease (AD) patients. However, the role of IGFBP2 during pre‐symptomatic AD remains unknown. Thus, we used longitudinal data acquired from the pre‐symptomatic PREVENT‐AD cohort to examine its possible contributions to AD pathophysiology.MethodFor initial cross‐sectional analyses, the Mini‐Mental State Examination was used to stage the participants (PREVENT‐AD, CCNA and Douglas cohorts) across the AD spectrum. Olink’s primer extension assay was used to measure cerebrospinal fluid (CSF) IGFBP2 levels. PREVENT‐AD participants were followed longitudinally for 6‐8 years. Annual visits included cognitive performance assessments, lumbar punctures and neuroimaging. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) evaluated five cognitive domains (immediate memory, delayed memory, attention, language and visuospatial abilities) and included a total summary score.ResultCSF IGFBP2 levels were significantly reduced in MCI (p < 0.001) and AD participants (p = 0.027 and p < 0.001 respectively), relative to controls (Figure 1). In the PREVENT‐AD cohort, baseline CSF IGFBP2 levels were negatively correlated with RBANS cognitive performance trajectory slopes estimated over the course of 6 to 8 years, for the delayed memory (p = 0.003), visuospatial (p = 0.008) and total scale indices (p = 0.021) (Figure 2). However, baseline CSF IGFBP2 levels were not associated with cognitive decline for the immediate memory (p = 0.162), attention (p = 0.890) and language (p = 0.841) indices (Figure 3). Finally, in the PREVENT‐AD cohort, baseline CSF IGFBP2 levels were negatively correlated with baseline left entorhinal cortex volume (p = 0.011), but were not correlated with right entorhinal cortex volume (p = 0.868)(Figure 4).ConclusionOur results suggest that IGFBP2 may exhibit a bi‐directional association with AD stage pathology. Our findings revealed that IGFBP2 is strongly correlated with early cognitive decline in the delayed memory and visuospatial domains, in pre‐symptomatic individuals.
Genetic and glial heterogeneity in Alzheimer disease
Authors: Brase Logan , You Shih‐Feng , Novotny Brenna C , Soriano‐Tarraga Carolina , Morris John C. , Bateman Randall J. , Perrin Richard J. , McDade Eric , Goate Alison , Karch Celeste M. , Benitez Bruno A. , Cruchaga Carlos , Harari Oscar ,   Dominantly Inherited Alzheimer Network (DIAN)
Published: December 2022

AbstractBackgroundAlzheimer disease (AD) has substantial genetic, molecular, and cellular heterogeneity associated with its etiology. However, much of the downstream cell‐type‐specific transcriptional and functional ramifications of familial mutations and high‐risk variants for AD are still poorly understood.MethodsWe generated unsorted single‐nuclei transcriptomic profiles (snRNA‐seq) of parietal lobes from 67 donors from the Knight ADRC and DIAN cohorts [1] to investigate altered molecular pathways in healthy and AD individuals, including carriers of pathogenic mutations in APP and PSEN1 and risk variants in TREM2. We validated our findings using snRNA‐seq from the DLPFC from the ROS‐MAP cohort [2]. We analyzed ∼294K high‐quality nuclei and identified six major cell populations. We performed deep subclustering analysis for the distinct cell types to reveal and characterize transcriptional states associated with AD genetic variants.ResultsCarriers of TREM2 AD risk variants p.R47H, p.R62H, and p.H157Y showed significantly increased proportions of nuclei in a reduced activation state (p = 3·29×10−2), consistent with in vitro experiments showing reduced microglial activation associated with these variants. [2, 3] (Figure). This state was replicated in the ROSMAP cohort (p = 7·4×10−107), and TREM2 p.R62H carriers showed a higher proportion of nuclei (p = 2·26×10−2). TREM2 risk variant carriers also showed an increased proportion of oligodendrocytes (Figure) exhibiting upregulation of 1,124 genes including TFEB (Knight ADRC p = 4·66×10−2; ROSMAP p = 2·48×10−2). Altered TFEB expression may be driven by the interaction of TREM2 with mTOR[4, 5]. TFEB is a central regulator of lysosomal biogenesis[6, 7] and represses myelination at different developmental stages.[8] Altered TFEB signaling has been implicated in several neurodegenerative diseases.[6, 9]ConclusionsAD pathogenic and risk variants are sufficient to alter human brains' transcriptional and cellular landscape. While TREM2 is mainly expressed in microglia, and its loss of function mutations cause Nasu‐Hakola disease, which is characterized by loss of myelination, suggesting TREM2‐linked oligodendrocyte‐microglia crosstalk.[10] Here, we found that AD patients with TREM2 variants showed upregulation of TFEB and lysosomal pathways in a subset of oligodendrocytes likely driven by altered microglia transcriptional states. The integration of genetic and single‐cell molecular data facilitates our understanding of the heterogeneity of pathways, biological processes, and cell types affected in AD.
Developing a culturally tailored brain healthy diet intervention for older midwestern African Americans: a qualitative and quantitative study
Authors: Shaw Ashley R. , Vidoni Eric D , Burns Jeffrey M. , Berkley‐Patton Jannette , Sullivan Debra K 
Published: December 2022

AbstractBackgroundEmerging evidence suggests that up to half of Alzheimer’s disease (AD) cases are a result of modifiable risk factors related to poor diet such as blood pressure, obesity, and diabetes, all of which disproportionately affect African Americans (Johansen, Langton‐Frost, & Gottesman, 2020). Adherence to brain healthy diets has consistently been reported to be low among African Americans due to the lack of cultural considerations, such as soul food traditions (Epstein et al., 2012). Therefore, it is important to understand barriers and incorporate culture into a brain healthy diet design to improve adherence and reduce the risk of AD among African Americans.MethodWe conducted 6 semi‐structured focus groups (n = 40) to understand how older AA specific food preferences, preparation preferences, and community cooking class topics specific to the development and delivery of the intervention. Also, we conducted a needs assessment using surveys to further understand barriers and facilitators of dietary behaviors among older AA to further inform the development of a culturally tailored brain healthy dietary intervention.ResultA total of 40 African Americans participated in the study. The 6 focus groups generated 5 main themes including knowledge of dementia, practices shaping food choices and consumption, barriers impacting healthy dietary consumption, external instrumental support, and elements of culturally tailored brain healthy dietary intervention. The Mediterranean‐DASH Intervention for Neurodegenerative delay (MIND) diet model was most favored and seen more feasible to follow due to alignment with current lifestyle practices within the African American community. However, adjustments in the MIND diet are need increase acceptability. Findings from the needs assessment indicated that taste (30.8%) and cost (20.5%) were perceived barriers to eating healthy. Facilitators to eating healthy eating included nutrition education focused on eating healthy on a budget, meal planning and prepping that is delivered using virtual formats.ConclusionFindings from this study inform the development of a culturally tailored MIND diet incorporating soul food traditions (MIND‐SOUL) for African Americans.
US Adults’ Likelihood to Participate in Dementia Prevention Clinical Trials: Results from the National Poll on Healthy Aging
Authors: Cox Chelsea G. , Davis Matthew A. , Grill Joshua , Roberts J. Scott 
Published: December 2022

AbstractBackgroundRecruitment to dementia prevention clinical trials is challenging, and participants are not representative of US adults at risk. To inform future recruitment strategies, the field needs a better understanding of public attitudes toward dementia prevention research.MethodWe analyzed data from a subset of respondents to the University of Michigan National Poll on Healthy Aging (October 2018 wave), ages 50‐64, who completed a supplementary poll on dementia and brain health. Our primary outcome was likelihood to participate in a dementia prevention clinical trial (collapsed into very/somewhat likely versus not likely). Logistic regression models were used to examine associations between sociodemographic and dementia‐related factors (e.g., family history) and likelihood to participate. Among respondents not likely to participate, we examined frequency of reasons endorsed, stratified by age, sex, and race/ethnicity.ResultAmong 1,028 respondents, 44% reported being at least somewhat likely (12% very likely) to participate in a dementia prevention trial. In adjusted analyses, there were no differences in likelihood to participate by sociodemographic characteristics. Factors associated with higher likelihood to participate were higher perceived likelihood to develop dementia [adjusted OR, 2.04 (95% CI, 1.53, 2.72)], family history of dementia [adjusted OR, 1.89 (95% CI, 1.38, 2.57)], and having discussed dementia prevention with a doctor [adjusted OR, 2.31 (95% CI, 1.20, 4.44)]. Among the 570 respondents not likely to participate, 38% did not want to be a guinea pig, 24% did not think dementia would affect them, 22% thought there would be too high a chance for harm, 16% indicated it would take too much time, and 5% reported fear of learning information about oneself. Compared to females, males more frequently endorsed that dementia would not affect them (28% versus 20%; p = 0.03). No other differences among demographic groups were observed.ConclusionIn this study, perceived risk of dementia, family history, and discussion of prevention with a doctor were associated with likelihood to participate in a dementia prevention clinical trial, whereas sociodemographic factors including race/ethnicity were not. This suggests that campaigns focused on dementia risk and prevention may be effective tools to improve enrollment rates, regardless of target community.
Brain network segregation attenuates tau spreading in Alzheimer’s disease
Authors: Steward Anna , Biel Davina , Luan Ying , Brendel Matthias , Dewenter Anna , Roemer Sebastian Niclas , Rubinski Anna , Dichgans Martin , Ewers Michael , Franzmeier Nicolai 
Published: December 2022

AbstractBackgroundIn Alzheimer’s disease (AD), the functional connectome plays a key role in the trans‐neuronal spreading of tau pathology, a key driver of cognitive decline. The functional connectome is comprised of segregated, but communicating networks which lose segregation with age, resulting in an overall more diffuse connectome. Prior neuroimaging studies have found an association between weaker network segregation and faster symptom manifestation in AD, however, it is unclear if this association occurs because of a more diffuse connectome facilitating connectivity‐mediated tau spreading.MethodTo investigate if network segregation is linked with accelerated tau spreading, we combined resting‐state fMRI with longitudinal Flortaucipir tau‐PET in 36 healthy controls and 57 biomarker‐defined AD subjects spanning the preclinical to dementia spectrum. Network segregation (the between to within‐network connectivity balance) was estimated at the subject level with resting‐state‐fMRI‐determined connectivity between 400 cortical regions of interest belonging to seven major networks.ResultResults revealed that higher baseline entorhinal tau‐PET (Braak I) was associated with accelerated tau accumulation in the rest of the brain (Braak III‐VI) in the AD and pooled sample, yet subjects with stronger network segregation exhibited an attenuated effect (Fig.1A). Additionally, through modelling patient‐specific tau epicentres we similarly demonstrated that subjects with high epicentre segregation exhibited an attenuated tau accumulation rate in the remaining brain (Fig1B).ConclusionIn line with the concept that tau spreads trans‐neuronally, our findings suggest that a more diffuse network topology facilitates tau expansion and further emphasises the critical role of the functional connectome in routing the spread of tau.