bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi‐Marker Approach to Reducing the Intermediate Range of a High Accuracy 2‐Cutoff Plasma p‐Tau 217 Test for Amyloid Detection
Authors: Wilson David H , Khare Meenakshi , Wolfe Michele , Sheehy Patrick , Copeland Karen , Hesterberg Lyndal , Vasko Ann‐Jeanette , van der Flier Wiesje M. , van Harten Argonde C. , Verberk Inge M.W. , Teunissen Charlotte , Miller Mike 
Published: January 2025

AbstractBackgroundp‐Tau 217 is considered the most accurate single plasma biomarker for detecting amyloid pathology. Recent draft Alzheimer’s Association criteria for diagnosing Alzheimer’s recommends that p‐Tau 217 tests be designed with two cut‐offs in recognition of signal overlap between diseased and non‐diseased subjects. Two cutoffs maximizes the accuracy of the test, but leaves a diagnostic intermediate zone with uncertainty of amyloid status. It is desirable to minimize the indeterminant zone to reduce the number of patients receiving uncertain results. We investigated whether the inclusion of plasma amyloid b42/40 ratio, NfL, and GFAP into a multi‐marker logistic regression model including p‐Tau 217 would enable amyloid classification of uncertain results from p‐Tau 217 alone.MethodWe optimized diagnostic thresholds for the Simoa LucentAD p‐Tau 217 plasma test to achieve ≥90% accuracy for MCI and AD patients across 2 independent cohorts (Bio‐Hermes, n = 242, Amsterdam Dementia Cohort, n = 737) representing divergent clinical settings, comparator methods, and geographic/ethnic/racial/mean age samplings. Across these diverse cohorts, the intermediate zone was 32.9%. Next we tested all samples for amyloid ratio, NfL, and GFAP using the Simoa N4PE kit. Multivariate logistic regression modeling was performed on all biomarker results to arrive at a probability scale. Samples with uncertain p‐Tau 217 results were re‐classified based on their probabilities being outside 90% lower and upper boundaries of the multi‐marker intermediate zone.ResultTables 1 and 2 exhibit preliminary amyloid classification results for p‐Tau 217 alone and the multi‐marker model respectively. “Amyloid Status” was determined by amyloid PET (Bio‐Hermes) or CSF biomarkers (Amsterdam). The multi‐marker model enabled amyloid classifications for 189 previously uncertain results. 137 uncertain results were re‐classified as positive (accuracy 88%), and 52 uncertain results were re‐classified as negative (accuracy 87%), reducing the intermediate zone 2.4‐fold from 32.9% to 13.7%.ConclusionPrevious studies have found no benefit to combining additional AD‐relevant biomarkers with p‐Tau 217 to enhance accuracy. We show for the first time that additional biomarkers reduces the intermediate zone of a 2‐cutoff p‐Tau 217 test while preserving high accuracy. This finding can help provide amyloid status certainty for a greater number of symptomatic patients undergoing evaluation for Alzheimer’s.
Understanding Biomarker Discordance: MRI and PET Phenotypes Shed Light on Alzheimer’s Pathology
Authors: Gunasekaran Tamil Iniyan , Lee Annie J. , Lao Patrick J. , Gutierrez Jose , Manly Jennifer J. , Gu Yian , Brickman Adam M. , Honig Lawrence S. , Vardarajan Badri N. , Mayeux Richard 
Published: January 2025

AbstractBackgroundPlasma biomarkers for Alzheimer’s disease (AD) are indicators of neuropathological changes. Biomarker cutoffs may not consistently indicate the presence or absence of a pathology. Discrepant biomarker levels are observed in some cognitively normal subjects and patients with clinically diagnosed AD, with some asymptomatic individuals having biomarker evidence of AD pathophysiology and some symptomatic individuals without evidence of AD pathophysiology. The purpose of this study is to understand the discordant biomarker levels among CN and AD using phenotypes from MRI and PET images.MethodWe measured phosphorylated tau 181 (P‐tau181) in plasma from 685 individuals in the Washington Heights Inwood Columbia Aging Project (WHICAP; Mean age = 76.52; women = 64.59%; non‐Hispanic Whites = 29.61%, African Americans = 30.62%; Caribbean Hispanics = 37.30%) and characterized them as biomarker positive based on a ptau181 cutoff of 2.648 pg/mL: 556 cognitively normal (CN, 241 biomarker+), 59 mild cognitively impaired (MCI, 26 biomarker+), and 70 had clinical AD (40 biomarker+). We used MRI (n = 685) and [18F] Florbetaben (FBB) Aβ PET in 167 (24.2%) individuals, and [18F]‐MK‐6420 tau PET 23 (3.36%) individuals) to compare white matter hyperintensity volume (WMH), hippocampus volume, number of silent brain infarcts (SBI), Aβ standard uptake value ratios (SUVR), and tau SUVR among the six biomarker groups (CN‐, CN+, MCI‐, MCI+, AD‐, AD+) with ANCOVA model adjusting for age, sex, and ethnicity.ResultThe AD+ group had larger WMH volume (P = 2.81×10−26), smaller hippocampus volume (P = 5.34×10−04), higher Aβ SUVR (P = 2.26×10−03) and tau SUVR (P = 8.11×10−04) compared to the CN‐. The AD‐ group had larger WMH volumes (P = 1.96×10−04) and smaller hippocampal volume (P = 0.039) to CN‐. When compared to the AD‐ group, the AD+ group had larger WMH volume (P = 4.34×10−03). The CN+ group had a larger WMH volume (P = 4.17×10−03) and smaller hippocampal volume (P = 4.13×10−05) than CN‐ group. Both MCI+ (P = 0.048) and MCI‐ (P = 0.022) groups showed smaller hippocampal volume compared with the CN‐ group. Except for hippocampal volume, no other phenotypes demonstrated statistical significance in the MCI+ and MCI‐ groups.ConclusionMRI and PET phenotypes exhibited a strong association with pathophysiological changes in the AD+ group. Specifically, MRI phenotypes such as WMH volume and hippocampal volume could be instrumental in characterizing AD pathophysiology, even with discrepancies in biomarker profiles.
Restoring activity‐dependent synaptic and microglial transcriptomic alterations in late‐stage Alzheimer’s Disease
Authors: Latif‐Hernandez Amira , III Robert R. Butler , Moran‐Losada Patricia , Yang Tao , Tran Kevin C , Liu Harry , Wyss‐Coray Tony , Longo Frank M. 
Published: January 2025

AbstractBackgroundActivity‐dependent transcription is crucial in establishing the late phase of long‐term potentiation (L‐LTP), which is altered in Alzheimer’s disease (AD). TrkB and TrkC signaling‐activator (BD10‐2) reduces AD‐related synaptic dysfunction. We determined whether the synapse‐sparing effects of BD10‐2 are reflected in transcriptional changes following L‐LTP induction.MethodWe orally administered BD10‐2 or vehicle to 13‐month old APPL/S and WT mice, daily for 3 months. We measured L‐LTP‐dependent gene expression through RNA‐sequencing in hippocampal slices with or without induction of Theta‐Burst‐Stimulation (TBS)‐induced LTP.ResultL‐LTP induction failed in APPL/S‐Veh but was restored in APPL/S‐BD2‐10 mice similarly to WT‐veh. Analysis of overlap enrichment between mouse TBS‐dependent gene expression and human AD‐relevant modules, revealed: (1) greater downregulation of neuronal genes by TBS in WT‐Veh and APPL/S‐BD10‐2 than in APPL/S‐Veh; and (2) upregulation of microglial associated AD‐enriched genes by TBS in all groups.ConclusionBD10‐2 prevented AD‐related LTP deficits and restored activity‐dependent AD‐related gene transcription.
Stable Isotope Labelling Kinetics (SILK) tracing of neurofilament light in human cerebrospinal fluid and brain tissue
Authors: Giovannucci Tatiana A. , Leckey Claire A. , Coulton John , Zetterberg Henrik , Elbert Donald L. , Bateman Randall J. , Mills Kevin , Wray Selina , Ghoshal Nupur , Sato Chihiro , Paterson Ross W. 
Published: January 2025

AbstractBackgroundNeurofilament light protein (NfL) is a promising biomarker of neuronal injury and neurodegeneration. NfL levels in cerebrospinal fluid (CSF) and blood provide information about disease progression and are increasingly relied on as outcome measure in clinical trials. Understanding NfL kinetics in vivo is critical for interpreting NfL in response to new events where a steady state cannot be assumed, such as acute injury, disease onset or progression, or response to disease‐modifying therapies.MethodWe infused human participants with diagnosed primary tauopathies (progressive supranuclear palsy, n = 5; corticobasal syndrome, n = 3; behavioural variant frontotemporal dementia, n = 2) with a stable isotope tracer (13C6‐leucine) and collected CSF by lumbar puncture at 4, 14, 20, 60 and 120 days post‐labelling. In addition, post‐mortem brain tissue from three participants who were infused with the tracer 18, 44 and 50 months earlier were homogenised and biochemically fractionated to separate the soluble and insoluble fraction. NfL was enriched in all samples via immunoprecipitation. The ratio of labelled to unlabelled NfL was measured monitoring proteotypic peptides using established targeted mass spectrometry workflows to quantitate the tracer‐to‐tracee ratio (TTR).ResultAnalysis of CSF detected low labelling of NfL (0.04 – 0.36% TTR) by 120 days that was comparable to the TTR levels detected in the soluble brain fraction. There was NfL present in the insoluble fraction (2.87% of the total NfL at 18‐, 8.87% at 44‐ and 14.03% at 50‐months post‐mortem, averaged across several NfL peptides), with different relative abundances of NfL domains between these fractions. Interestingly, the 13C6‐labelled NfL signal detected in the insoluble fraction was more abundant, despite a higher recovery of total NfL in the soluble fraction.ConclusionNfL turnover in vivo is remarkably slow as it is scarcely captured by 120 days post‐labelling. The labelling results from brain tissue suggest that in these cases of primary tauopathies newly‐synthesized NfL might be delocalized to a pool of protein of low solubility that does not contribute to NfL levels in CSF. Current experiments are addressing whether newly‐synthesized NfL might be sequestered into pathological inclusions.
Body mass index moderates the relationship between the apnea‐hypopnea index and CSF biomarker of activated microglia
Authors: Bink Julia , Ma Yue , Mander Bryce A , Plante David T , Carboni Margherita , Wild Norbert , Chin Nathaniel A. , Okonkwo Ozioma C , Carlsson Cynthia M. , Gleason Carey E. , Asthana Sanjay , Johnson Sterling C. , Blennow Kaj , Zetterberg Henrik , Benca Ruth M , Bendlin Barbara B. 
Published: January 2025

AbstractBackgroundPrior studies suggest that obstructive sleep apnea (OSA) may be associated with Alzheimer’s disease (AD) pathology, including Aβ42/Aβ40 and p‐Tau181. However, less is known about relationships between OSA and non‐AD pathology, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), S100, chitinase 3‐like 1 (YKL40), and soluble triggering receptor expressed on myeloid cells 2 (sTREM2), as well as the effect of potential moderating factors. The present study investigated the relationship between the apnea‐hypopnea index (AHI) and cerebrospinal fluid (CSF) biomarkers of AD and related pathology.MethodIn this cross‐sectional study, 73 cognitively unimpaired adults with no prior OSA diagnosis underwent an overnight PSG and/or testing with an at home ApneaLink. Participants completed a lumbar puncture to determine Aβ42/Aβ40, pTau181, NfL, GFAP, s100, YKL‐40, and sTREM2 as part of the Roche NeuroToolKit research platform (Roche International). Relationships between AHI and CSF biomarkers were tested using multiple linear regression adjusting for age, sex, APOE genotype, and BMI. Given prior studies suggesting potential interaction effects, we also examined interactions between AHI and APOE and interactions between AHI and BMI.ResultAHI determined using PSG and at home Apnealink were highly correlated (r = 0.78, p < 0.01). There were no significant main effects of AHI on any of the CSF biomarkers, controlling for covariates (p > 0.05). Further, there was no significant interaction between APOE and AHI (p > 0.05). We found a significant interaction between BMI and AHI, such that participants with lower BMI showed higher sTREM2 with greater AHI, (p = 0.02; Figure 1). However, this positive relationship diminished with higher BMI.ConclusionOSA and obesity are intrinsically linked processes, however prior studies in sleep have also shown that these factors have interactive effects on several outcomes, including measures of inflammation and cognitive function. Here, we found that individuals who had lower BMI showed a potentially deleterious effect of AHI on measures of microglial activation. Additional studies are needed to determine whether these results are due to possible protective effects of higher BMI, or differences in sleep quality among individuals with high and low BMI.
TOP‐LINE CSF Biomarker Outcomes from the Phase 2 Clinical Trial SHINE in Alzheimer’s Patients
Authors: Caro Valentina Di , Cho Eunah , Knezovich Nicole , Blennow Kaj , Zetterberg Henrik , Teunissen Charlotte , Grundman Michael , Caggiano Anthony O , Hamby Mary E. 
Published: January 2025

AbstractBackgroundA Phase 2 randomized, double‐blind, placebo‐controlled 6‐month trial, SHINE (NCT03507790), was designed to include up to 144 participants with mild to moderate Alzheimer’s disease (AD) to study the effects of the sigma‐2 receptor (S2R) modulator CT1812 on cognition, safety, and biomarkers. CSF canonical and exploratory biomarkers were assessed to determine treatment effects with CT1812.MethodParticipants (n = 153) received a daily oral dose of either CT1812 (100 mg or 300 mg) or placebo during the treatment period of 6‐months. The levels of CSF biomarkers Aβ40, Aβ42, pTau181, tTau, Nfl were measured by Lumipulse, neurogranin, GFAP and α‐synuclein by ELISA, SNAP‐25 and synaptotagmin by IP‐LC‐MS assay, and Aβ42/40 ratio calculated. An ANCOVA model was used to assess treatment effects comparing change from baseline values of CT1812 vs placebo. Significance was assessed at p<0.05 using 2‐tailed tests, and p‐values determined. A p‐value of <0.10 but >0.05 was considered evidence of a trend.ResultAt the end of the 6‐month treatment period, change from baseline levels and assessment of treatment effects (p<0.05) for CSF Aβ40, Aβ42, pTau181, tTau, Nfl, neurogranin, GFAP, SNAP‐25, synaptotagmin, and αSynuclein will be presented for the full trial. In an interim analysis of the first 24 participants, a significant (p<0.05) change from placebo for Aβ40, Aβ42 was observed with 300 mg of CT1812, along with trends of changes in other biomarkers. Treatment effects for all biomarkers assessed in the entire study will be presented. We hypothesize that the effect seen in lowering Aβ40 and Aβ42 will persist in the full analysis.ConclusionUnderstanding the effect of CT1812 on CSF biomarkers should lend support towards the clinical development of CT1812 for AD. The significant decrease in Aβ42and Ab40 levels may reflect pathway engagement given the mechanism of action of action of CT1812, and replication of this finding in the fully completed trial is prudent.
Cardiovascular health predicts working memory decline among cognitively healthy older African Americans
Authors: Amoateng Brad , Sheikh Mustafa , Fausto Bernadette A. , Gluck Mark A. 
Published: January 2025

AbstractBackgroundAfrican Americans are at increased risk for cardiovascular‐related health problems (e.g., hypertension, cardiovascular disease, stroke, obesity) and cognitive dysfunction, including Alzheimer’s disease (AD)1,2. However, few studies have looked at the longitudinal influence of cardiovascular health and cognitive function in older African Americans. This study investigated the relationship between cardiovascular health markers and cognition in older African Americans.Method836 participants were drawn from Pathways to Healthy Aging in African Americans, a longitudinal cohort study at Rutgers University–Newark. Participants completed a battery of self‐reported health and demographic questionnaires, neuropsychological tests, and a short physical battery of both anthropometric and physical assessments. Linear mixed models were used to examine the relationship between baseline cardiovascular health markers and cognitive function up to 6 years of follow up.ResultHigher diastolic blood pressure was significantly associated with worse Trail Making Test Part A (B = 0.035, p < .001), and Montreal Cognitive Assessment (B = 0.085, p = .0029) performance across time. Higher systolic blood pressure was significantly associated with poorer Trail Making Test Part A (B = 0.017, p < .001) and MoCA (B = 0.055, p < .001). Higher resting heart rate was significantly associated with worse Trail Making Test Part A (B = 0.018, p = .0031) and Part B (B = 0.085, p = .013), Controlled Oral Word Association Test (B = 0.036, p = .025), and Montreal Cognitive Assessment performance across time (B = 0.047, p = .046).ConclusionIn cognitively unimpaired older African Americans, cardiovascular health markers are predictive biomarkers for early working memory decline in preclinical AD. Our findings may inform holistic clinical decision‐making in AD prevention and personalized AD monitoring in patients with cardiovascular disease.
Porphyrin–based Vinylene–linked 3D Covalent Organic Framework with Unprecedented cya Topology for Photocatalytic H2O2 Production
Authors: Gong Zihan , Gao Ying , Li Jing , Cai Zichen , Liu Naifang , Jiang Jianzhuang 
Published: January 2025

Designing and realizing new topologies represent one of the most important ways toward developing new structures and functionalities for molecule–based frameworks including SOFs, MOFs, and COFs. Herein, Aldol condensation between 5,10,15,20–tetrayl(tetrakis(([1,1':3',1''–terphenyl]–4,4''–dicarbaldehyde)))–porphyrin (TTEP) and 2,4,6–trimethyl–1,3,5–triazine (TMT) affords the vinylene–linked 3D covalent organic framework Por–COF–cya. Powder X–ray diffraction (PXRD) in combination with structural simulation reveals its high crystalline structure with an unprecedented cya topology in the molecule–based frameworks reported thus far. Por–COF–cya displayed polycrystallinity and possessed high permanent porosity. Especially, the incorporation of light–harvesting porphyrin unit and vinylene linkages in Por–COF–cya enables a conjugation effect within the framework, endowing it with a photocatalytic H2O2 production rate of 2209 μmol g−1h−1 in pure aqueous solution under visible–light irradiation (λ > 400 nm). Inclusion of the guest molecules TTF into the pores of Por–COF–cya results in a donor–acceptor system TTF@Por–COF–cya, enhancing the photocatalytic activity with H2O2 production rate of 6994 μmol g−1h−1. This work paves a new way for the development of new topological functional molecule–based frameworks toward diverse application potentials.
Synthesis and Characterization of Silver Nanoparticles‐Filled and Polyvinyl Alcohol‐Grafted Copolymer Composites for Column Adsorption and Photochemical Degradation of p‐Nitrophenol
Authors: Debnath Pampa , Ray Samit Kumar 
Published: January 2025

ABSTRACTPolyvinyl alcohol (PVA), sodium polyacrylate, and polyacrylonitrile are very effective for stabilizing and controlling the size of nanoparticles. Thus, PVA was grafted to the copolymer of acrylonitrile (AN) and acrylic acid/sodium acrylate (AA/NaAA) using N,N′‐methylenebisacrylamide comonomer–crosslinker (MBA). Silver nanoparticles (AgNPs) were synthesized in situ in the polymerization mixtures by reduction of AgNO3 with ascorbic acid. These nanocomposites were characterized and used for the removal and photocatalytic degradation of p‐nitrophenol (PNP) from water. Based on the Box–Behnken design of the response surface methodology, the nanocomposite prepared with the AN:NaAA/AA molar ratio/MBA wt.%/PVA wt.% of 5:1/0.5/2 and impregnated with AgNPs of 18–30 nm average size (noted as PVACP5Ag) showed the optimized results. PVACP5Ag showed the equilibrium batch adsorption (qe, mg/g) of 240.93 from 50 mg/L PNP in water and a qe of 36.2 in fixed bed adsorption at a feed inlet concentration (mgL−1)/inflow rate (mLmin−1)/bed height (mm) of 50/30/30. The same composite showed a degradation of 96% after 7 min of exposure to sunlight in the presence of NaBH4 with a first‐order rate constant of 0.3 min−1 and 90.3% degradation after 110 min of exposure with a first‐order rate constant of 0.01 min−1 without any reducing agent.
Dimethylacridine Based Emitters for Non‐Doped Organic Light‐Emitting Diodes with Improved Efficiency
Authors: Zhang Min , Zhang Xingye , Yang Ning , Wu Yibing , Ouyang Xinhua 
Published: January 2025

AbstractOrganic light‐emitting diodes (OLEDs) has been attracting much extensive interest owing to their advantages of high‐definition and flexible displays. Many advances have been focused on boosting the efficiency and stability. Two innovative dimethylacridine‐based emitters, 1,1,2,2‐tetrakis(4‐ (2,7‐di‐tert‐butyl‐9,9‐dimethylacridin‐10(9H)‐yl)phenyl ethene (AcTPE), and bis(4‐(2,7‐di‐tert‐butyl‐9,9‐dimethylacridin‐10(9H)‐yl)phenyl)methanone (Ac2BP) were designed and synthesized, in which TPE‐baesed AcTPE presents AIE properties, and with the phenyl as spacer between the DMAC and carbony, aryl‐ketone‐based Ac2BP doesn't show AIE properties due to the absence of restriction of intramolecular rotations. As the electron‐withdrawing ability of carbonyl, well‐matched energy levels of the Ac2BP improve carriers transfer and hole injecting process in devices, resulting an efficient green emission with a maximum PE of of 5.64 lm W−1, a EQE of 10.56 % and a maximum CE of 18.27 cd A−1. They are much higher than that of AcTPE‐based devices (3.45 cd A−1, 1.18 lm W−1, and 1.46 %). This study provides a promising design strategy for efficient OLED emitters of aryl‐ketone‐architecture.
The Impact of Silver Codoping on Tb3+ Luminescence in Lithium Tetraborate Glasses
Authors: Kindrat I. I. , Padlyak B. V. , Drzewiecki A. , Teslyuk I. M. , Adamiv V. T. 
Published: January 2025

ABSTRACTSpectroscopic properties of Tb‐doped and Tb‐Ag codoped lithium tetraborate (LTB) glasses with Li2B4O7 (or Li2O–2B2O3) composition are investigated and analysed using electron paramagnetic resonance (EPR), optical absorption, photoluminescence (PL) and photoluminescence excitation (PLE) spectra, PL decay kinetics and absolute quantum yield (QY) measurements. PL spectra of the investigated glasses show numerous narrow emission bands corresponding to the 5D4 → 7FJ (J = 6–0) and 5D3 → 7FJ (J = 5–3) transitions of Tb3+ (4f8) ions. The most intense PL band of Tb3+ ions at 541 nm (5D4 → 7F5 transition) is characterised by a lifetime slightly exceeding 2.6 ms. PL spectra of the Ag‐containing glass show two broad weakly resolved emission bands in the violet‐green spectral range attributed to Ag+ ions and nonplasmonic Ag nanoclusters. Decay kinetics of these bands are nonmonoexponential, characterised by an average lifetime in the microsecond range. A significant enhancement of the PL intensity and PL QY of Tb3+ ions was observed in Tb‐Ag codoped LTB glass in comparison with Tb‐doped LTB glass. The excitation energy transfer (EET) mechanisms from Ag+ ions and Ag nanoclusters to Tb3+ ions were explored.