bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood pressure is associated with tau pathology independent of beta‐amyloid
Authors: Rizvi Batool , Lao Patrick J , Brickman Adam M 
Published: December 2020

AbstractBackgroundHigh blood pressure is a risk factor of Alzheimer’s disease (AD) but it is unclear whether it plays a direct role in disease pathogenesis. Recent animal work indicates that induced ischemic disease promotes tau hyperphosphorylation, suggesting that vascular risk factors may directly contribute to AD via neurofibrillary tangle pathology. We examined the relationship between blood pressure indicators and tau pathology, measured with Flortaucipir PET, in early Braak regions among older adults with mild cognitive impairment (MCI) or no cognitive impairment (NC) in the Alzheimer’s Disease Neuroimaging Initiative (ADNI).MethodA total of 141 ADNI 2 participants (75.6 + 6.72 years old, 53.2% women, 92% White, 33.3% MCI) who underwent Florbetapir (AV‐45) amyloid and Flortaucipir (AV‐1451) tau PET imaging were included in the analyses. Diastolic (DBP) and systolic blood (SBP) pressure measurements from screening visits were considered. We derived mean arterial pressure (MAP; SBP+2(DBP)), pulse pressure (SBP–DBP), and characterized participants as Stage 2 hypertensive (systolic BP > 140 and/or diastolic BP > 90). We examined the association of each blood pressure indicator with tau standardized uptake value ratios (SUVR) in the entorhinal cortex (EC), adjusting for age, sex/gender, MCI diagnosis, time interval between the screening visit and PET visit (4.5 + 1.17 SD years prior to the PET scan), and a cortical amyloid summary measure. We tested interactions between MCI diagnosis and blood pressure.ResultIndependent of amyloid pathology, higher systolic pressure (β=0.217, p=0.009), higher MAP (β=0.186, p=0.021), and hypertension (β=0.165, p=0.044) were associated with increased tau deposition in the entorhinal cortex. Of the covariates, amyloid SUVR (βs=0.301‐0.303, p<0.001), and MCI diagnosis (βs=0.165‐0.189, p=0.031–0.049) were also associated with entorhinal cortex tau. The association between MAP and entorhinal cortex tau was stronger in MCI relative to controls (MCI: β=0.330, p=0.037, NC: β=0.086, p=0.321).ConclusionHigh blood pressure is associated with future neurofibrillary tangle pathology in early Braak regions, independently of amyloid. Our results are consistent with reports of earlier life hypertension as risk for later life AD. Together with results from recent animal studies, they highlight a potential pathway in which vascular factors promote AD pathogenesis via tau.
Peripheral inflammatory biomarkers and risk factors of dementia in the Chilean GERO cohort
Authors: Orellana Paulina , Duran‐Aniotz Claudia , Baez Pablo , Gomez Rodrigo , Lillo Patricia , Villagra Roque , Thumala Daniela , Toledo Carolina , Cabello Victoria , Henriquez Fernando , Parrao Teresa , Gonzalez Christian , Slachevsky Andrea 
Published: December 2020

AbstractBackgroundDementia is one of the mean causes of disability in elderly. Peripheral inflammatory biomarkers and ApoE‐ε4 allele have been described as important biological risk factors of dementia in Caucasian population. Currently, there is scarce information about the specific age‐related and predisposition factors to develop dementia in Latino populations. The aim of this study is to investigate these biological risks factors in Chilean elderly with healthy and pathological brain ageing.MethodWe evaluated and quantified plasma samples obtained from the GERO cohort (114 elderly subjects, >70 years, classified in 51 subjects with subjective cognitive complaint (SCC) and 63 with mild cognitive impairment (MCI)), in addition to 36 healthy brain controls (HBC) and 31 subjects with Alzheimer’s disease dementia (ADD). Genotyping of ApoE gene was analyzed by qPCR. We analyzed inflammatory biomarkers using Luminex technique including IL‐2, IL‐6, IL‐10, TNF‐α, CRP and SAP proteins. All subjects receive a clinical and neuropsychological assessment.ResultCRP protein was found significant decrease expression in SCC and ADD groups compared to MCI and HBC (p=0.048). In SAP protein was found a significant decrease in expression in the SSC (p=0.04) and MCI (p=0.0178) groups compared to HBC. It was observed a positive correlation in the SCC, MCI and ADD groups with the IL‐6 and TNFα, and, SAP and CRP. A negative correlation between IL‐2, IL‐6 and IL‐10 cytokines was found with Direct Span Digit test, which assess attentional capacity. Also was identified a negative correlation between SAP protein and the Free and Cued Selective Reminding Test (FCSRT), which assess verbal episodic memory, and IL‐10 cytokine and Montreal Cognitive Assessment (MoCA), which assess global cognition. Finally, a positive correlation was found in CRP protein with Pfeffer Functional Activity Questionnaire. Frequency of the ApoE‐ε4 allele, was significantly higher in ADD (52%) and SCC (27%) patients than controls and MCI (p=1x10‐4).ConclusionThe results shown correlations between the different inflammatory proteins and performance in neuropsychological test suggesting that inflammatory biomarkers are associated with pathological brain ageing. The correlations in SCC and MCI are not being reported previously. Additionally, the frequency of ApoE‐ε4 allele in ADD group is higher than worldwide populations.
Longitudinal grey matter changes in the healthy aging brain as measured by voxel‐based morphometry
Authors: Neufeld Nicole M , Parker Ashleigh F , Gawryluk Jodie 
Published: December 2020

AbstractBackgroundIn order to understand the changes that occur in the brain over the course of neurodegenerative disorders, it is imperative to establish how the brain changes over time under healthy conditions (Mattson & Arumugam, 2018). Older adulthood is associated with normal age‐related declines in cognitive functioning (Klimova et al., 2017). However, there are inconsistencies in the literature regarding associated changes in grey matter, with some reporting atrophy across the whole brain and others reporting focal atrophy, localized in the frontal and temporal regions (Pergher et al., 2019; Squarzoni et al., 2018). The current study took a longitudinal approach to investigate changes in grey matter over four years in healthy aging.Methods3T T1 anatomical magnetic resonance images (MRI) were obtained from 16 healthy older adults (7 male, 9 female; mean age 74.38 ± 4.52 years at baseline) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database at two time points, four years apart. Voxel‐based morphometry (VBM) analyses were carried out using FMRIB’s Software Library to examine within‐subject changes in grey matter over time.ResultsFigure 1 depicts regions where there was significant atrophy (p<0.05, corrected for multiple comparisons) in grey matter at four‐year follow‐up compared to baseline. Specifically, VBM results indicated atrophy in distributed areas including bilateral frontal and temporal regions as well as in the hippocampi, bilaterally. However, there were no significant changes in cognitive performance over these four years.ConclusionsThe current findings reveal atrophy in multiple regions, including the temporal lobes despite normal cognitive performance over the course of four years in healthy aging. Similar regions are known to be affected in Alzheimer’s disease and associated with cognitive decline (Minkova et al., 2017). Follow up work will aim to replicate the current findings in a larger sample and to examine the relationship between cognitive performance and grey matter volume. Developing an understanding of changes in brain structure and function that occur over time in healthy aging will allow for improved interpretation of changes in neurodegenerative conditions, such as Alzheimer’s disease.
Asparagine residue 368 is involved in Alzheimer’s disease tau strain‐specific aggregation
Authors: Shimonaka Shotaro , Elahi Montasir , Matsumoto Shin‐Ei , Ishiguro Koichi , Hasegawa Masato , Hattori Nobutaka , Motoi Yumiko 
Published: December 2020

AbstractBackgroundIn tauopathies, tau forms pathogenic fibrils with distinct conformations (termed ‘tau strains’) and acts as an aggregation “seed” promoting the conversion of normal tau into isomorphic fibrils. Previous research showed that the aggregation core of tau fibril covers the carboxy‐terminal region (243–406) and differs among the diseases. However, the mechanisms by which distinct fibrous structures are formed and inherited in comparison to normal tau via templated aggregation are still unknown. Here, we sought to identify the key sequences of seed‐dependent aggregation.MethodTo identify sequences for which deletion reduces tau aggregation, SH‐SY5Y cells expressing a series of 10 partial deletion (Del 1–10, covering 244–400 aa) mutants of tau‐CTF24 (243–441 aa) were treated with tau seeds prepared from a different tauopathy patient’s brain [Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD)] or recombinant tau and then, seed‐dependent tau aggregation was assessed biochemically. Furthermore, we systematically repeated cellular tau aggregation assays for the delineation of shorter deletion sites to identify the minimum sequence responsible for tau aggregation.ResultWe found that the Del 8 mutant lacking 353–368 aa showed significantly decreased aggregation in both cellular and in vitro models. Mutagenesis studies revealed that Asn368 mutation suppressed tau aggregation triggered by an AD‐tau seed, but not using other tauopathies seeds, including PSP and CBD. Similar effects were also observed with Ala replacement of the Ser320 residue, which was arranged facing inwards toward Asn368, in the AD‐tau core structure that was determined recently by means of cryo‐electron microscopy.ConclusionOur study suggested that 353–368 aa is a novel aggregation‐responsible sequence other than PHF6 and PHF6*, and within this sequence, the Asn368 residue plays a role in strain‐specific tau aggregation in different tauopathies, possibly along with Ser320.
Effect of mindfulness intervention on salivary Aβ‐42 levels in community‐dwelling older adults with mild cognitive impairment: A randomized controlled trial
Authors: Ng Ted Kheng Siang , Tan Crystal Tze Ying , Nur Fadzillah , Wee Sin Tho , Goh Lee Gan , Kua Ee‐Heok , Larbi Anis , Mahendran Rathi , Slowey Paul 
Published: December 2020

AbstractBackgroundFew randomized controlled trials investigated the effects of mindfulness intervention on older adults diagnosed with mild cognitive impairment (MCI). Specifically, there has been a scarcity of literature on the potential benefit of a mindfulness intervention on biomarker for AD hallmark. Thus, we conducted a secondary analysis on bio‐banked salivary samples of a pilot randomized controlled trial, examining whether Mindful Awareness Practice (MAP) improved salivary Aβ‐42 levels in older adults with MCI.Method55 community‐dwelling older adults diagnosed with MCI were randomized into either the treatment arm, MAP, or the active control arm, health education program (HEP). Interventions were carried out for 9 months. Field and laboratory investigators who were blinded to the treatment allocations collected saliva samples at baseline, 3‐month, and 9‐month follow‐ups. Salivary Aβ‐42 levels were quantified using a newly validated commercial assay. Linear‐mixed models were used to examine the effect of MAP on salivary Aβ‐42 levels.ResultCompared to the control arm, MAP participants had no significantly changed Aβ‐42 levels throughout the 9‐month intervention period. Exploratory subgroup analyses by either sex or MCI‐subtypes (amnestic and non‐amnestic) also did not show significantly changed Aβ‐42 levels.ConclusionMAP did not improve salivary Aβ‐42 levels in community‐dwelling older adults with MCI. Although our previous findings showed the potential of MAP in improving biomarkers of systemic inflammation and synaptic functions, the current findings suggest that mindfulness intervention may not be effective in ameliorating AD hallmark. A more specific/targeted psychosocial intervention may be needed to improve AD pathology in patients with MCI.
Art and dementia education in times of COVID‐19
Authors: Mateus‐Berr Ruth , Al‐Mousli Luna , Carli Christina May Yan , Faißt Verena , Gharashir Nargol , Girotto Lara , Greisberger Eva , Gruber Vanessa Lea , Guserl Stefanie , Hausner Ida Johanna , Muzler Susa , Ngo Nha , Sanglhuber Anna , Schaitl Jasmin , Scharler‐Plotnik Pia Moana , Schroll Alexandra , Schober Michaela 
Published: December 2020

AbstractBackgroundAround the world, there will be one new case of dementia every 3 seconds. 152 million people are worldwide living with dementia in 2050, by then 2 billion people will be over 60 years of age. There are negative attitudes towards elderly people and ageism is extremely common. Young people often know somebody in their families with dementia and most of the time do not know how to handle it. This project designs the first arts‐based schooling strategy for empathy for people with dementia, creates a dementia friendly generation, age‐friendly environments, supports young people to understand dementia. Objective of the project is to develop artistic strategies to strengthen empathic abilities with arts‐based methods & interdisciplinary collaboration between people with & without dementia. Stress is a daily challenge faced by family caregivers working with people with dementia, isolation became another demanding situation. Isolation has an impact on health, therefore workshops were designed for caregivers and students in quarantine to engage in the questions ‘How can art‐based research affect intergenerational well‐being of people with dementia and students? And ‘How can these means encourage the handling of the topic dementia?’MethodArt and design‐based online‐workshops enable family caregivers and students in isolation to take salutogenetic perspectives. Methods of embodied & experiential learning were applied, an interdisciplinary approach as new methodology of teaching awareness about dementia by innovative arts‐based pedagogies. The workshops on Body & Senses engage in body awareness, trigger senses and exploring movement and touch. The workshop Storytelling collects and rewrites memories from different perspectives and narratives. Other workshops create images in innovative ways, through investigating one’s environment, explore documentary material and designing tangible visualization.ResultWorkshops resulted in positive feedback and knowledge about dementia by all participants. 281 people, aged between 13‐65 participated at these workshops. Most of them were students, others engaged in family care in isolation.ConclusionArt‐based research facilitated creative approach, self‐awareness about one's own resources and empathy and knowledge growth on dementia.Highlights: art‐based research methods contributed to well‐being in isolation; creative workshops involved participants to experience resources; awareness growth on dementia.
The role of cardiometabolic risk in the association between accumulation of affective symptoms across adulthood and midlife cognitive function
Authors: John Amber , Desai Roopal , Richards Marcus , Gaysina Darya , Stott Joshua 
Published: December 2020

AbstractBackgroundAffective symptoms, such as depression and anxiety, are associated with cognition in midlife and later life. However, the role of cardiometabolic risk in this association has not been examined. The aim of this research was to investigate how cardiometabolic risk contributes to associations between affective symptoms and midlife cognition.MethodData were used from the National Child Development Study (NCDS), a sample of people born in Britain during one week in 1958. Affective symptoms were assessed at ages 23, 33, and 42 and a measure of accumulation derived. A cardiometabolic risk score was calculated from nine cardiometabolic biomarkers at age 44. Measures of memory, verbal fluency, and information processing were available at age 50.ResultFully adjusted path models indicated significant indirect associations between affective symptoms and midlife immediate memory (β=‐0.002, SE=0.001, p=.009), delayed memory (β=‐0.002, SE=0.001, p=.02) and verbal fluency (β=‐0.002, SE=0.001, p=.045) through cardiometabolic risk. Cardiometabolic risk did not predict subsequent affective symptoms or cognition at age 50.ConclusionThese findings suggest that cardiometabolic risk may play an important indirect role in the association between affective symptoms and cognitive function (memory and verbal fluency). Results contribute to understanding of biological mechanisms underlying associations between affective symptoms and cognitive ageing, which can have implications for early detection of, and intervention for, those at risk of poorer cognitive outcomes.
Cellular dependency analysis identifies genes implicated in Alzheimer’s disease (AD) as potential treatment targets
Authors: Jaladanki Suraj K , Malave Gabriel Santos , Huang Kuan‐lin 
Published: December 2020

AbstractBackgroundGenes involved in the progression of Alzheimer’s disease (AD) have been identified, but these genes have not been studied in the context of CRISPR knockouts and RNAi screens to reveal cell‐specific vulnerabilities.MethodA list of 105 AD‐associated genes, found through genome‐wide association studies (GWAS) and gene expression network analyses, was compiled. Expression and knock‐down/out dependency data for over 700 cell lines was obtained through the Cancer Dependency Map (DepMap). The expression‐associated dependencies were specifically examined in three tissue types that may be relevant to AD etiology: hematopoietic and lymphoid tissue, central nervous system, and autonomic ganglia.Result
SPI1, MEF2C, GAB2, and ABCC11 in hematopoietic and lymphoid tissue cell lines were established as genes of interest since their genetic knockouts specifically affected cells showing high expression of these genes. Other genes exhibiting expression‐associated dependencies include ACTG1 in autonomic ganglia and GLS in central nervous system cell lines. Investigating these genes for expression and dependency patterns in their respective AD tissue of interest highlighted cell lines that had the most significant decrease in cell survival and growth after CRISPR knockout or RNAi screen.Conclusion
SPI1, MEF2C, GAB2, and ABCC11 demonstrated expression‐associated dependencies in cell lines of AD‐associated tissues, and present as potential targets for AD.
Loss of synaptogyrin‐3 rescues tau‐induced memory defects and synaptic loss in the presence of microglial activation
Authors: Largo‐Barrientos Pablo , de Strooper Bart , Spires‐Jones Tara , de Wit Joris , Uytterhoeven Valerie , Verstreken Patrik 
Published: December 2020

AbstractBackgroundWe previously identified synaptic vesicle protein Synaptogyrin‐3 as a physical interactor of Tau. Upon mutations and/or hyperphosrylation, Tau accumulates at synapses, binds to Synaptogyrin‐3 and clusters synaptic vesicles, reducing vesicle mobility and neurotransmitter release (McInnes et al., Neuron 2018).MethodWe generated a synaptogyrin‐3 knockout mouse usign CRISPR/Cas9. We crossed synaptogyrin‐3 knockout mice with mice expressing human P301S mice (PS19 mouse line) to generate Tau P301S; synaptogyrin‐3
+/‐ mice. We assessed several aspects of mutant Tau‐induced pathology using biochemistry, electrophysiology, histology and behavior experiments.ResultWe show that loss of Synaptogyrin‐3 is benign in mice, but strongly rescues mutant Tau‐induced defects in long‐term synaptic plasticity and working memory. It also significantly rescues the synaptic loss caused by mutant Tau. However, Tau‐induced neuroinflammation remains clearly upregulated when we remove synaptogyrin‐3.ConclusionInteraction of Tau and Synaptogyrin‐3 leads to pre‐synaptic dysfunction, and pre‐synaptic defects caused by mutant Tau are enough to drive defects in cognitive tasks. On the other hand, neuroinflammation is not sufficient to induce synaptic loss and these processes are separately induced in response to mutant Tau.
Investigating the pathological mechanisms linking depression and Alzheimer’s disease
Authors: Dunnett Sophie Louise , Cheung Kylie KY , Chang Raymond Chuen‐Chung 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is a devastating neurodegenerative disease characterized by the presence of tau tangles, amyloid beta plaques and neuroinflammation. Although the mechanisms underlying AD are not fully understand, several key risk factors for developing AD have been identified, such as depression. Previous work from our group, using a corticosterone‐induced model of depression in rats, has found that depression leads to tau phosphorylation and its displacement from microtubules, mislocalization and aggregation within neurons. The aims of my project are to continue investigating whether depression leads to other pathological tau alterations, such as acetylation, and to investigate the relationship between tau and neuroinflammation in the context of depression, focusing on the complement and toll‐like receptor (TLR) signaling pathways.MethodIn this project, we are using a corticosterone‐induced model of depression. Corticosterone is administered daily to Sprague‐Dawley (SD) rats for 21 days. Afterwards, a series of behavioral tests are performed including the Open Field test, the Novel Object Recognition task and the Forced Swim Test to assess their anxiety, memory and depressive behaviors, respectively. Afterwards, brain samples are collected from the animals to conduct immunohistochemical analysis, qPCR and western blot.ResultFollowing 21 days of corticosterone administration, subjects display decreased adrenal and bodyweight, and anxiety‐like behaviors. Thus far, qPCR data demonstrates that there are increases in TLR4, as well as downstream elements in its signaling pathway, in the hippocampus.ConclusionIn depression, alterations to the TLR4 signaling pathway are observed in the hippocampus. We will further investigate this pathway, its interplay with the complement system, and how these alterations impact tau pathology.