bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Mobile Toolbox for assessing cognition in older adults: associations with standardized cognitive testing and amyloid and tau PET
Authors: Jutten Roos J. , Burling Jessa , Campbell Emily C , Roy Chloe , Properzi Michael J , Amariglio Rebecca E. , Marshall Gad A , Johnson Keith A. , Sperling Reisa A. , Papp Kathryn V. , Rentz Dorene M. 
Published: December 2023

AbstractBackgroundRemote, smartphone‐based cognitive assessments such as the Mobile Toolbox (MTB) can improve our ability to detect subtle, yet meaningful cognitive changes that are affected early on by Alzheimer’s disease (AD) pathology. The goal of our study was to investigate which MTB tests are sensitive to subtle cognitive deficits due to early amyloid and tau deposition.MethodThe MTB will be administered to N = 100 clinically normal (CN) older adults who have retrospective and prospective clinical, cognitive and AD biomarker data from three well‐characterized prospective cohort‐studies of CN older adults: the Harvard Aging Brain Study and the affiliated Subjective Cognitive Decline and Instrumental Activities of Daily Living cohorts. The MTB includes six measures of fluid cognition, including episodic memory (Picture Sequence Memory and Face‐Name Associations), executive functions (Dimensional Change Card Sort, Flanker), working memory (Memory for Sequence), processing speed (Number‐Symbol Match), and two measures of crystallized cognition (Spelling and Vocabulary). Using confirmatory factor analysis, MTB baseline data will be used to determine which MTB tests are most strongly associated with established clinical assessments (i.e., measures included in the Preclinical Alzheimer’s Cognitive Composite‐5 [PACC5]) as well as amyloid and tau biomarkers on positron emission tomography (PET) imaging.ResultPreliminary MTB data was available on 15 participants (age 74.3±8.2, 63% female, 16.6±2.9 years of education, MMSE 29±1.5). Table 1 shows exploratory correlation analyses, revealing that both MTB crystallized measures were associated with education but not age or sex. As expected, worse performance on MTB memory measures were associated with lower PACC5 scores, and greater amyloid and tau burden, albeit at trend‐level. Executive function and processing speed measures were not related to amyloid but did show associations with entorhinal tau.ConclusionWhile preliminary, these findings suggest that the MTB may help elucidate the subtle cognitive deficits that are associated with early AD pathology. In addition to memory measures, the MTB fluid measures capture various aspects of cognitive function that are also relevant to preclinical AD. Data collection is ongoing, and next steps include examining which (combination of) MTB measures are most sensitive for detecting emerging AD pathology and to track cognitive change over time.
Clinical phenotype of the A431E mutation in PSEN1 arising as a founder effect from the Mexican State of Jalisco
Authors: Sánchez González Victor J. , Orozco Maribel , Figuera‐Villanueva Luis Eduardo , Matute Esmeralda , Ringman John M 
Published: December 2023

AbstractBackgroundAutosomal dominant Alzheimer’s disease (ADAD) is a rare subtype of AD in which the disease is caused by mutations in the PSEN1, APP, or PSEN2 genes which are essentially fully penetrant. Mutations in PSEN1 are most common and several populations have been described within which the same causative variant appears to have arisen from a common founder. The study of such populations allows for an increased sensitivity for identification of genetic and non‐genetic variables affecting phenotype and for studying the effects of interventions.MethodsWe summarize 20 years of work characterizing the population with ADAD due to the A431E mutation in PSEN1.ResultsNine families with 60 members with ADAD due to the A431E PSEN1 mutation were originally reported by investigators in Mexico City in 2006 (Yescas et al). They noted a mean age of onset of 40 years and 1 of 13 probands had spastic paraparesis (SP). All probands hailed from the Los Altos region of Jalisco State and all affected persons shared the same CA and GT dinucleotide microsatellite alleles surrounding the PSEN1 gene, suggesting a common origin of the haplotype. U.S. Investigators then reported an additional 15 families with the A431E variant. Mean age of onset was 39.5 years and 9/20 probands (45%) had SP. In 2020 Dumois‐Petersen et al, reported their experience of 46 index patients in Guadalajara from families in which 560 persons were identified to be at 50% risk of inheriting the mutation. Mean age of onset of 42.5 years with at least a moderate degree of leg spasticity being present in 77% in the first 2 years of symptoms. Memory loss was ubiquitous with language deficits ultimately being present in 82%, depression in 53%, delusions in 30%, Parkinsonism in 28%, cerebellar dysfunction in 23%, and seizures in 15%.ConclusionsCombined efforts in the U.S. and Mexico have allowed the identification of more than 100 superficially distinct families with the A431E PSEN1 mutation and an estimated number of 1,260 identifiable at‐risk persons, providing an attractive target for both mutation‐specific genetic interventions and for anti‐AD therapy in general.P30AG066530, U01AG051218, R01AG062007, R01AG069013
A single dose of lipopolysaccharide injection exacerbates synaptic engulfment by microglia, and dendritic spine loss in high‐fat diet‐induced obese rats
Authors: Chinchapo Thirathada , Chunchai Titikorn , Pintana Hiranya , Ongnok Benjamin , Pantiya Patcharapong , Jinawong Kewarin , Arunsak Busarin , Janjek Sornram , Kerdphoo Sasiwan , Apaijai Nattayaporn , Pratchayasakul Wasana , Chattipakorn Nipon , Chattipakorn Siriporn C 
Published: December 2023

AbstractBackgroundDiet‐induced obesity can lead to develop endotoxemia and cognitive decline (1). A previous study in Alzheimer’s disease model demonstrated that an increase in the colocalization of C1q, a classical complement protein, and microglia occurred, when those microglia increased synaptic engulfment, resulting in increased synaptic‐pruning process and synaptic loss (2). However, the effects of lipopolysaccharide (LPS) as endotoxin on peripheral inflammation, blood‐brain barrier(BBB) integrity, brain oxidative stress, synaptic engulfment by microglia, synaptic plasticity, and cognitive function in high‐fat diet‐induced obese rats have never been investigated.MethodSixteen male Wistar rats were randomly assigned to receive either a normal diet (ND, n = 8) or the high‐fat diet (HFD, n = 8) for 12 weeks. All animals in each dietary group were subsequently assigned into 2 subgroups (n = 4 /subgroup) to receive either a single dose of vehicle (1 ml of 0.9% normal saline solution, intraperitoneal (i.p.) injection, or LPS (0.5 mg/kg, i.p.). After the injections for 12‐16 hours, all animals were measured for cognitive function and the blood was collected. Then, animals were sacrificed, and their brains and spleens were obtained for further investigation.ResultAll HFD‐fed rats exhibited peripheral inflammation as indicated by increased spleen IL‐1β protein levels, BBB disruption as indicated by the reduction of hippocampal claudia‐5 protein levels, and increased brain oxidative stress as indicated by the increased brain malondialdehyde levels (p<0.05, Figure 1). Interestingly, LPS‐treated ND‐fed rats and vehicle‐treated HFD‐fed rats equally impaired microglial function by increasing synaptic engulfment as indicated by the increase in C1q colocalized in microglia and the decreased dendritic spine density (p<0.05, Figure 1). The results demonstrated that these parameters were aggravated in LPS‐treated HFD‐fed rats. Lastly, all HFD‐fed rats decreased the preference index of novel object location and recognition test suggesting long‐term HFD consumption caused cognitive decline (p<0.05, Figure 1).ConclusionLong‐term HFD consumption, but not LPS alone, caused cognitive decline by increasing peripheral inflammation, disrupting BBB integrity, increasing brain oxidative stress, increasing synaptic engulfment by microglia, and decreasing synaptic plasticity. Microglia are susceptible to impair their function in response to LPS, which potentially worsen brain pathologies in obese condition.
Evaluation of Helianthus annuus Flower Extract on Biomarkers of Alzheimer’s Disease
Authors: Joshi Ankur , Malviya Dr Neelesh 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is a slowly progressive disease of the brain that is characterized by the impairment of memory and eventually by disturbances in reasoning, planning, language, and perception. Amyloid β‐peptide (Aβ) is main source of oxidative stress in AD because it can acquire a free‐radical state that contributes to its toxic effects. Aβ‐induced cytotoxicity is caused by intracellular accumulation ofreactive oxygen species, which leads to lipid peroxidation and cell death. Helianthus annuus flower is known for its nutritional value and having many medicinal benefits as well. Helianthus annuus flower contain many medicinally essential phytoconstituents, such as phenol, flavonoid, and carotenoid.MethodSTZ administration through route such as intracebroventricular or intraperitoneal injection produces reduced cognition and increased cerebral aggregated Aβ fragments, total tau protein, and Aβ deposits. These changes were accompanied with decreased glycogen synthase kinase (GSK‐3) alpha/beta ratio (phosphorylated/total) in the brain. Administration of STZ in a rodent’s brain has been shown to produce neuroinflammation, oxidative stress and biochemical alterations, which is considered to be a valid experimental model of the early pathophysiological changes in neurodegenerative disease.ResultTwo doses (100 and 200 mg/kg) of the flower extract from Helianthus annuus were given over the course of seven days. The standard agent utilised was piracetam (120 mg/kg). Oral administration of Helianthus annuus flower extract resulted in a considerable reduction in A1‐40 58 0.21 (100mg/kg) and 53 0.79 (200mg/kg) and A1‐42 17 0.89 (100mg/kg) and 15 1.02 (200mg/kg). Helianthus annuus flower extract increased the levels of the following brain antioxidant enzymes at 100 mg/kg and 200 mg/kg, respectively: CAT (15.5 2.8** and 14.0 1.12**), SOD (13.5 1.4** and 18.3 1.7**, GSH (203.3 15.3** and 218.0 13.5**), TBARS (200.3 7.3** and 208.0 11.0**). AChE activity was significantly decreased when Helianthus annuus flower extract was taken orally at doses of 100 mg/kg and 200 mg/kg, respectively.ConclusionData of the present study revealed that Helianthus annuus flower significantly decreased the brain Amyloid β 1‐42 and AChE activity in rats. Data revealed that administration of both Helianthus annuus flower (100mg/kg) and Helianthus annuus flower (200mg/kg) increased the activity of SOD and CAT.
Identification of novel drug targets for Alzheimer’s disease by integrating genetics and proteomes from brain and blood
Authors: Ou Ya‐nan 
Published: December 2023

AbstractBackgroundGenome‐wide association studies (GWASs) have discovered numerous risk genes for Alzheimer’s disease (AD), but how these genes confer AD risk is challenging to decipher.MethodTo efficiently transform genetic associations into drug targets for AD, we employed an integrative analytical pipeline using proteomes in brain and blood by systematically applying proteome‐wide association study (PWAS), Mendelian randomization (MR) and Bayesian colocalization.ResultCollectively, we identified the brain protein abundance of 7 genes (ACE, ICA1L, TOM1L2, SNX32, EPHX2, CTSH, and RTFDC1) are causal in AD (P<0.05/proteins identified for PWAS and MR; PPH4>80% for Bayesian colocalization). The proteins encoded by these genes were mainly expressed on the surface of glutamatergic neurons and astrocytes. Of them, ACE with its protein abundance was also identified in significant association with AD on the blood‐based studies and showed significance at the transcriptomic level. SNX32 was also found to be associated with AD at the blood transcriptomic level.ConclusionOur current study results on genetic, proteomic and transcriptomic approaches has identified compelling genes, which may provide important leads to design future functional studies and potential drug targets for AD.
Caspase‐dependent Apoptosis Inhibition Improves Cognitive Function in Myocardial Infarction Rats
Authors: Jinawong Kewarin , Apaijai Nattayaporn , Piamsiri Chanon , Maneechote Chayadom , Pintana Hiranya , Chattipakorn Nipon , Chattipakorn Siriporn C 
Published: December 2023

AbstractBackgroundCognitive impairment was frequently found following myocardial infarction (MI). Apoptosis, particularly in the hippocampal area, has been proposed as a mechanism involving in the cognitive impairment through the initiation of brain cell death and subsequently dendritic spine loss. The hypothesis of this study is that the inhibition of apoptosis using a pan‐caspase inhibitor (Z‐VAD‐FMK) improves hippocampal dependent cognitive function in MI rats via attenuating brain apoptosis and dendritic spine lossMethodMale Wistar rats were divided into sham operation or permanent left anterior descending coronary artery ligation‐induced MI. After one week, MI rats with LVEF less than 50% were randomly assigned to one of three interventions: (1) MI‐vehicle (DMSO), (2) Enalapril as a positive control (10 mg/kg/day, PO), and (3) A pan‐caspase inhibitor (Z‐VAD‐FMK, 1 mg/kg/day, IP). All rats received the intervention for 4 weeks, then cardiac function and hippocampal‐dependent cognitive function were assessed before they were sacrificed. Hippocampal dendritic spine density and apoptotic protein expression were determined.ResultMI‐vehicle rats exhibited cardiac dysfunction (as shown by a decrease in %LVEF), cognitive impairment (as shown by decreased %preference of novel object recognition), and hippocampal dendritic spine loss. Furthermore, our data showed that apoptosis was significantly increased (as shown by increased cleaved‐caspase 3/Pro‐caspase 3 levels) in MI‐vehicle rats, compared with the sham rats (as shown in Figure). Treatment with Z‐VAD‐FMK and enalapril equally improved cardiac function, cognitive function, and increased hippocampal dendritic spine density, compared with the MI‐vehicle rats. Z‐VAD‐FMK demonstrated a greater benefit in reducing apoptosis than enalapril in the brain of MI rats.ConclusionApoptosis inhibitor shared similar efficacy with enalapril in improving cognitive function through suppressing brain apoptosis and restoring hippocampal dendritic spine density in MI rats.
Are noradrenergic and orexinergic systems contributing to sleep‐wake patterns in early and late‐onset Alzheimer’s Disease?
Authors: Falgàs Martínez Neus , Muñoz‐Moreno Emma , Mayà Gerard , Muñoz‐Lopetegui Amaia , Marrero‐González Paula , Val‐Guardiola Andrea , Guillén Núria , Sarto Jordi , Bosch Beatriz , Balasa Mircea , Fernandez‐Villullas Guadalupe , Antonell Anna , Walsh Christine M , Ruoff Leslie , Joan Santamaria , Bargalló Núria , Lladó Albert , Morales‐Ruiz Manuel , Iranzo Álex , Grinberg Lea T. , Sanchez‐Valle Raquel 
Published: December 2023

AbstractBackgroundNeuropsychiatric symptoms, including sleep‐wake disturbances, are more common in Early‐onset Alzheimer’s disease (EOAD) than in Late‐onset AD (LOAD)(Falgàs, EurJNeurol2022). The pattern of tau‐related degeneration of wake and sleep‐promoting neurons determine sleep‐wake profiles in neurodegenerative disorders (Oh, JAMANeurol2022). We hypothesize that distinct patterns of noradrenergic (locus coeruleus‐LC) and orexigenic (hypothalamus‐HT) degeneration contribute for the differential sleep‐wake patterns between EOAD and LOAD.MethodA group of 21 participants (7 EOAD, 18 LOAD) with a diagnosis of AD confirmed by cerebrospinal fluid biomarkers (CSF) were recruited from Hospital Clínic de Barcelona. Participants underwent sleep questionnaires (Pittsburg Sleep Quality Inventory‐PSQI and Epworth Sleepiness Scale‐ESS), 2‐week actigraphy (MotionWatch8, CamnTech) and 3T‐neuromelanin‐sensitive MRI to measure locus coeruleus (LC) and hypothalamus (HT) volumes. Sleep, napping, and circadian parameters were obtained (MotionWare).ResultThe preliminary results showed no differences in sex (71vs.61% women) or disease stage (CDR 0.5: 85% vs.72%). The amnestic phenotype was prevalent (100 vs.78%). EOAD had longer daytime napping (93.2±74 vs. 58.2±28min, p<0.05), later fell asleep times (0:42am vs. 11:30pm, p<0.05) and higher central phase measure (4.4±0.5 vs. 3.5±1 h, p<0.05, midpoint between fell asleep and wake‐up) than LOAD. Daytime napping correlated with ESS (r = 0.53, p<0.01). Other parameters such as actual sleep time, sleep efficiency, sleep latency, or fragmentation index showed no differences. PSQI did not correlate to any measures. LC‐volumes were lower in EOAD than in LOAD (24.4±7mm3 vs. 33.3±6 p<0.01). In contrast, HT‐ trended towards higher volumes in EOAD (416.8±38 vs. 392.9±36, p = 0.09), being inversely correlated to the age at onset (r = ‐0.47, p<0.05). The central phase measure was inversely correlated to LC‐volumes (r = ‐0.47, p<0.05) but not to HT. Further analyses with increased sample size, CSF noradrenaline and orexin will be performed.ConclusionGreater daytime sleepiness and circadian dysfunction could be main differing traits regarding sleep‐wake patterns between EOAD and LOAD. An opposite pattern of degeneration within wake‐promoting systems consisting of higher degeneration of the LC‐noradrenergic system and relative preservation of the HT‐orexigenic in EOAD in contrast to LOAD might underlie differing sleep‐wake phenotypes. Age‐related hypothalamic volume loss can be adding to AD driven loss resulting in higher volumes in EOAD.
Factors associated with dementia attitudes in an adolescent cohort: structural equation modelling
Authors: Hassan Esra , Hicks Ben , Tabet Naji , Farina Nicolas 
Published: December 2023

AbstractBackgroundDementia related stigma is a key barrier to people living well with dementia. The global action plan on the public health response to dementia outlines the need to tackle the stigma towards dementia among the general population (WHO, 2017). Adolescents represent an under researched group among the general population but may already have experience of dementia and will become future carers or healthcare workers. Adolescents are ideal targets for anti‐stigma initiatives since the adolescence period has a key role in attitude formation. Understanding the factors involved in dementia attitude formation is useful when developing anti‐stigma initiatives. This study aims to identify predictors of dementia attitudes in adolescents.MethodThis is a cross‐sectional study using secondary data analysis. 470 participants aged 12‐15 years old from secondary schools in the Southeast of England, United Kingdom completed validated questionnaires relating to dementia attitudes (KIDS and Brief A‐ADS) as well as demographic information. A path analysis via a structural equation model was used to test for direct and mediatory effects between dementia attitudes, contact, career interest, empathy and sex.ResultThe overall fit of the model was very good, χ2(16) = 16.913, p = .15, CFI = .99, GFI = .99, AGFI = .97, TLI = .98, RMSEA = .03, Pclose = .82. There was a significant direct effect observed between the following paths; sex to dementia attitudes (p = .001), attitudes to willingness to work with people with dementia, (p < 0.001), empathy to dementia attitudes (p = .01), contact to empathy (p = .01), and empathy to contact (p < 0.001). Within the final structural equation model, empathy was a key mediator between contact and dementia attitudes.ConclusionThis study highlights the pivotal role that contact with dementia can have in influencing dementia attitudes in adolescents with empathy a key mediator between contact and dementia attitudes. The translational significance of this work is that it provides organizations with the knowledge needed to create effective policy and interventions. Interventions that use contact should consider stimulating empathetic responses to shape dementia attitudes.
Proteomic comparison between CSF samples and CSF‐derived EVs from patients with Alzheimer’s disease, Parkinson’s disease and Lewy Body dementia
Authors: Hirschberg Yael , Boonen Kurt , Engelborgs Sebastiaan , Vermeiren Yannick , Mertens Inge 
Published: December 2023

AbstractBackgroundExtracellular vesicles (EVs) have recently been considered as a potential biomarker source for a variety of diseases, including neurodegenerative disorders. EVs are important mediators of intercellular communication due to their capacity to transfer genetic material, lipids and proteins. By means of their communication role, interesting biomarkers are often enriched in EVs compared to total biofluid. In this study, this hypothesis is tested as untargeted proteomics is performed on both CSF samples and CSF‐derived EV samples from the same cohort with different dementia diseases.MethodCSF samples were collected from 297 patients (with Alzheimer’s disease (AD), Parkinson’s disease (PD), PD with cognitive deficit (PDCD), PD with dementia (PDD), Lewy Body dementia (LBD)) and healthy controls (HC). Furthermore, EVs were obtained from 500µL of the same CSF samples, isolated by SmartSEC HT. Total protein quantification was measured using absorbance at 280nm for CSF samples, and by fluorescence (NanoOrangeTM) for CSF‐derived EV samples. For both types of sample, LC‐MS/MS based proteomics analyses were performed.ResultTotal protein quantification showed multiple significant differences between all groups, both in CSF samples and in CSF‐derived EV samples. In both types of sample, PDCD group showed the highest protein concentration after normalization. In regard to LC‐MS/MS results, a first analysis resulted in a total of 3036 identified proteins (1564 protein groups) for the CSF samples, and 6627 proteins (3360 protein groups) for the CSF‐derived EV samples. The current analyses show four statistically differentially expressed proteins between CSF‐derived EV samples from HC and AD, AD and PD, LBD and PDCD. By the time of AAIC2023, also CSF samples will be analysed and a comparison will be drawn between both types of sample.ConclusionAs more in‐depth proteomic analyses will be performed by AAIC2023, a definite conclusion will be given at the conference. For now, already differences in total protein concentration were observed between the different disease groups and LC‐MS/MS of CSF‐derived EV samples resulted in four statistically differentially expressed proteins.