bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roles of CCNY in the amyloid pathology of Alzheimer’s disease
Authors: Kim Hark Kyun , Park Jeonghye , Park Mikyoung , Jo Dong‐Gyu 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD), the most common form of dementia, has three major pathological features; Aβ plaque, tau tangles, and neuroinflammation. Many studies have focused on developing treatments for AD; however, many clinical trials have failed. It recently has been discussed that depletion of Cyclin Y(CCNY) ameliorates impaired memory function by inhibiting memory plasticity by AMPA receptor. However, very little is known about the molecular mechanisms between CCNY and AD progression. Also, it remains controversial whether CCNY accelerates amyloid pathology or halts it.MethodWe crossed CCNY KO mice with 5xFAD, making 4 groups for the project; WT, CCNY KO, 5xFAD, 5xFAD;CCNY KO. Behavioural tests were conducted at the age of 10 months with Morris Water Maze(MWM) and Elevated Plus Maze(EPM). Brain tissue was collected using perfusion and then analyzed with ELISA, Immunohistochemistry (IHC), Thio‐flavin S(Thio‐S) staining, and RNA sequencing.ResultIn MWM and EPM tests, 5xFAD;CCNY−/− mice showed worse cognition level compared to 5xFAD mice. Analysis of Aβ1‐42 using ELISA illustrated the increased level of Aβ1‐42 in both cortex and hippocampus of 5xFAD;CCNY−/− mice. Aβ plaque level resulted from IHC sustainably upregulated in 5xFAD;CCNY−/− mice. Deficiency of CCNY described bigger size of senile plaques through Thio‐S staining in 5xFAD mice in contrast with 5xFAD mice. Activation of microglia was upregulated in 5xFAD;CCNY−/− mice confirmed via IHC.ConclusionIn this research, we investigated the role of CCNY in Aβ processing and neuroinflammation. This study demonstrates the association between CCNY and AD, illustrating CCNY as a regulator in the pathogenesis of Aβ plaque and as a candidate for AD therapy.
Effects of a contact‐free behavioral activation program using a digital device
Authors: Jung Jae Yeon , Park Sangmi , Kim Tae Hui 
Published: December 2023

AbstractBackgroundAccording to the literature, untreated depression among older adults is related to a higher likelihood of dementia (Saczynski et al., 2010). Behavioral Activation (BA) was developed as one of the effective interventions for decreasing depression. BA helps to understand and moderate daily behavior and emotions, which helps reduce depression. This study aimed to examine the effect of BA intervention using a digital device in older adults with depression. A digital device was used in this study to provide BA intervention stably in the face of a COVID‐19 pandemic.MethodA total of 60 older adults with depression participated in this study. Older adults in the intervention group (n = 30) used a tablet PC to participate in the daily one‐on‐one BA program from April to June 2022. Older adults in the control group (n = 30) used the companion robot (Hyodol). The Geriatric Depression Scale (GDS) and UCLA Loneliness Scale (UCLA) were applied to the pre‐test and post‐test. Chi‐squared test and Mann‐Whitney U test were conducted to test homogeneity between the two groups. Mann‐Whitney U test and a Wilcoxon signed rank test were conducted to compare the effect between two groups and changes within group. SPSS 26.0 was used for all analyses.ResultTwo groups were homogeneous in socio‐demographics. In the intervention group, the mean scores of the GDS and UCLA pre‐test were 9.7 (SD = 3.33) and 52.23 (SD = 5.40), respectively. In the control group, the pre‐test mean scores for GDS and UCLA were 10.63 (SD = 3.41) and 52.20 (SD = 6.26), respectively. The decreases in depression and loneliness in the intervention were statistically significant (depression: Z = ‐1.959, p < 0.01; loneliness: Z = ‐2.690, p < 0.01). The decrease in depression in the control group was statistically significant (Z = 2.824, p<0.01), but the decrease in loneliness was not statistically significant (Z = ‐1.494, p = 0.135) (table 1).ConclusionThe results support that BA program using digital device was effective in decreasing depression of older adults with depression. BA intervention using digital device can be considered as approaches for older adults with depression to prevent dementia.
Pharmacological inhibition of sFRP1 stimulates the non‐amyloidogenic pathway of amyloid precursor protein proteolytic processing
Authors: Lu Wenyan , Macyczko Jesse R , Martens Yuka A , Bu Guojun , Kanekiyo Takahisa , Li Yonghe 
Published: December 2023

AbstractBackgroundThe accumulation of the amyloid‐β (Aβ) aggregates in the brain is a key pathological event in the development of Alzheimer’s disease (AD). The α‐secretase ADAM10 is responsible for cleavage of the amyloid precursor protein (APP) through a non‐amyloidogenic pathway, thereby preventing the generation of pathogenic Aβ in the brain. Secreted frizzled related protein‐1 (sFRP1), an endogenous antagonist of Wnt signaling, has recently been identified as a key negative modulator of ADAM10. Importantly, proteomic studies reveal that unregulated sFRP1 is one of the top Aβ‐correlated proteins in the human AD brains.MethodsWe determined the therapeutic potential of specific sFRP1 WAY316606 in the N2a/APP695swe cells and patient‐specific iPSC‐derived cerebral organoids.ResultsWe herein demonstrated that treatment of sFRP1 inhibitor WAY316606 resulted in augmentation of ADAM10 activity, upregulation of soluble APP‐α (sAPPα) production, and inhibition of Aβ generation in the N2a/APP695swe cells. Moreover, WAY316606 significantly enhanced ADAM10 activity, decreased Aβ production and inhibited tau phosphorylation in human AD patient‐specific iPSC‐derived cerebral organoids.ConclusionOur findings indicate that sFRP1 is a promising therapeutic target for AD.
Understanding the role of the mitochondrial AD risk gene LACTB in myeloid cells.
Authors: Molina Carmen Romero , See Wen Yi , Liu Yiyuan , Marcora Edoardo , Goate Alison 
Published: December 2023

AbstractBackgroundAlthough powerful evidence points out the importance of myeloid cells in Alzheimer’s Disease (AD), the relevance of immunometabolism requires further exploration. Our analysis integrating AD genetics and myeloid cell genomics reported that lower LACTB expression is protective for AD, and proteomics studies have confirmed it (Wingo et al., 2021). LACTB is a mitochondrial serin protein that may influence mitochondrial morphology and bioenergetics. LACTB levels are associated with succinyl‐carnitine levels (Ghazalpour et al., 2014, Suhre et al., 2011), a metabolite that has been linked to AD risk (unpublished). LACTB has also been nominated as a tumor‐related and an obesity gene, but its function is not well defined.MethodsTHP1 cells were treated for 6 days with small‐interfering RNA to reduce LACTB expression. iPS cells were CRISPR‐edited to obtain LACTB knock‐out (KO) lines and differentiated into microglial cells (iMGLs). Functional experiments were performed. Collected samples were outsourced for RNAseq, metabolomic and lipidomic analysis.Resultswe characterized, for the first time, the role of LACTB in myeloid cells. We observed that LACTB expression is increased upon differentiation (in iMGLs compared to iPSC, and in THP1 macrophages compared to monocytes) and LPS stimulation. The downregulation of LACTB in THP1 led to an increase in succinyl‐carnitine (predicted to be protective for AD), and in histone succinylation, which may modify the cell epigenetics. Transcriptomics revealed an increase in the oxidative phosphorylation, which was validated by Seahorse experiments, and in the immune response to interferon and virus. In addition, LACTB knock‐down polarized THP1 macrophages towards a DAM‐like state. Lipidomics reported significant changes in specific lipid classes and a decrease in chain saturation. These experiments will be repeated in iMGLs.ConclusionLACTB may play a role in cell differentiation and response to stimulus in myeloid cells by modifying mitochondrial respiration and lipid metabolism. As future directions, iMGLs will be xenotransplanted in WT and 5xFAD mice to study LACTB role in vivo. Unlike other AD risk genes, LACTB encodes an enzyme, reduced expression is protective, and succinyl‐carnitine can be used as a biomarker, which highlights it as a promising AD therapeutic target.
Plasma GFAP accuracy and its association with brain pathology
Authors: Lorenzo Elizabeth Lucia Valeriano , Sanchez‐Juan Pascual , Rabano Alberto , Gonzales Alicia Ruiz , Burgueño‐García Iván , del Ser Teodoro 
Published: December 2023

AbstractBackgroundGlial fibrillary acidic protein (GFAP) is a biomarker of reactive astrogliosis that increases in the cerebrospinal fluid (CSF) and blood of many neurological and neurodegenerative conditions, including AD. Recent studies have shown that its determination in blood could be especially helpful in AD diagnosis. However, the neuropathological validation of GFAP as a biomarker of AD is still scarce, and only communications to scientific meetings have shown data with pathological validation.MethodIn our study, we aim to evaluate the effectiveness of plasma GFAP in detecting AD neuropathologically defined compared to cognitively unimpaired individuals and the correlation between GFAP levels and AD pathological lesions, estimated by their ADNC score, and other co‐pathologies. Plasma GFAP from cognitively unimpaired controls (n = 118) from the Vallecas cohort and sequential samples of definite AD cases (n = 101) from the Reina Sofia Centre were quantified by the SIMOA platform. On average, the neuropathological assessment was performed on AD patients 139 days after the last plasma collection.ResultPlasma GFAP concentrations were significantly increased in AD cases compared to controls, which allowed high discriminative power (area under the curve for plasma GFAP, 0.88‐0.96). Moreover, longitudinal increases in plasma GFAP levels of AD cases were significantly associated with post‐mortem brain pathology. The individuals who evidenced a higher ADNC stage at the post‐mortem experienced in life a significant increase in the rate of change of plasma GFAP across time, adjusted by age, extraction time of GFAP plasma, and estimated age of disease onset.ConclusionFor the first time, we correlated plasma GFAP levels with post‐mortem brain pathology with exceptionally low time intervals. This study confirms with autopsy data that plasma GFAP is a sensitive biomarker for detecting and tracking AD pathological changes.
Preventing cognitive decline using portable, non‐invasive sleep enhancement.
Authors: Züst Marc Alain 
Published: December 2023

AbstractBackgroundRecently, disturbed slow wave sleep (SWS) has been identified as an early, modifiable risk factor for dementia. SWS is crucial for memory and metabolic clearance functions, and lack of SWS causes these important functions to suffer, which in turn worsens cognitive decline. A vicious cycle forms between cognitive decline and loss of SWS. Improving SWS could be a way to break this cycle by providing the much‐needed opportunity for the brain to recuperate and ameliorate cognitive decline. We aim to enhance slow wave activity in older adults using phase‐locked auditory stimulation (PLAS). Our laboratory‐based results show that the magnitude of the physiological response to PLAS predicts improvement of memory functions and metabolic clearance. However, larger, long‐term studies in an ecologically valid setting are needed to assess the efficacy of PLAS for the improvement of sleep, memory, and metabolic clearance with the goal of preventing cognitive decline. Laboratory‐based studies quickly become economically and logistically unfeasible to achieve this goal.MethodWe propose a blinded, sham‐controlled cross‐over study utilizing home‐use devices to study the effect of PLAS on memory functions in 60 older adults with MCI or SCD. Participants will undergo verum‐ and sham‐PLAS in the comfort of their own home across a 12‐week study period. Cognitive performance will be assessed using engaging “serious games”, and blood will be sampled before‐ and after each experimental period to test levels of dementia‐related biomarkers (amyloid beta, pTau181 and 217, GFAP and NfL) and their response to PLAS.ResultWe expect PLAS to enhance sleep, which will lead to down‐stream effects on memory performance and metabolic clearance. Using a novel approach allowing brain‐age estimation from sleep‐electrophysiology, we hypothesize to see a “rejuvenating” effect of PLAS, restoring an electrophysiological profile typically seen in younger brains.ConclusionThis study could pave the way for PLAS‐capable home‐use devices as an affordable, non‐invasive tool to combat cognitive decline, and could lead to novel preventative applications for memory clinics, relieving their clinical burden and improving public health.
Reminiscence therapy and dementia care in the Pacific island of Guam
Authors: Twaddle Iain K. B. , Gutierrez Nikolas Jude 
Published: December 2023

AbstractBackgroundPersons living with dementia often find it easier to remember experiences from long ago—including memories from their youth and early adulthood—than to recall recent events, such as what they did that week or even earlier that day. As a result, trying to navigate the present can be stressful and overwhelming, while reminiscing about the past can be a comforting experience. Connecting with valued memories from the past often helps persons living with dementia maintain their identity, preserve their sense of self, and enhance their overall quality of life. Reminiscence therapy was developed as a way to achieve these benefits by engaging older adults in the exploration of cherished memories to improve cognitive functioning and psychological well‐being. In recent years, reminiscence therapy has become an effective and popular approach to providing therapeutic support for persons living with dementia.MethodTraining in reminiscence therapy was provided to family and professional caregivers in the Pacific island of Guam through a weekly online support group. Training sessions were designed to help caregivers learn to use reminiscence therapy with persons with dementia in culturally sensitive ways reflecting the oral storytelling traditions of Pacific island cultures. Session topics addressed: (1) the benefits of reminiscence for persons with dementia, from maintaining memory health to building confidence and self‐esteem; (2) guidance from local writers and historians on how to talk with older adults about their life histories, including questions to ask and ways to evoke favorite memories; (3) the use of historical photos from Guam as conversation starters for older adults with memory loss; and (4) sharing stories about growing up in Guam in the 1930s, '40s, ‘50s, and ‘60s, along with readings from memoirs based on this period.ResultParticipants reported highly positive experiences with implementing reminiscence therapy with persons with dementia in their care. The techniques helped persons with dementia to relive beautiful memories and to share these memories with their families.ConclusionProgram outcomes indicate that online training in reminiscence therapy is an effective way to teach caregivers skills to promote memory health and psychological well‐being for persons living with dementia.
Exploring barriers and facilitators for effective implementation of a physical activity project for people with dementia based on the consolidated framework for implementation research (CFIR)
Authors: Cardona Maria Isabel , Monsees Jessica , Schmachtenberg Tim , Thyrian Jochen René 
Published: December 2023

AbstractBackgroundAlthough recent studies show that physical activity (PA) may be beneficial for persons with dementia (PwD) [1], their participation in PA is still low compared to healthy older adults [2]. Therefore, there is a need for a further increase in comprehension regarding both barriers and facilitating factors leading to PA promotion in PwD. The main objective of this research was to assess barriers and facilitators during the implementation of a German project designed to promote PA among PwD using the Consolidated Framework for Implementation Research (CFIR) as an evaluation framework.MethodSemi‐structured interviews were conducted with project leaders and sports trainers participating in the project “Sport bewegt Menschen mit Demenz” (Sport moves people with dementia). This project consisted in implementing PA initiatives for PwD including sport clubs from four German sports associations. In addition, the CFIR guided data collection and analysis.ResultsIn total, twenty‐one participants were part of the study. The most frequent barriers identified were lack of funding and involvement of persons with dementia. The most reported facilitators were engaged sports trainers/project leaders and positive implementation climate within sports clubs. Future fields of action should be focused on developing networks for improved communication between involved actors; assuring financial opportunities from local, regional, or national institutions; designing enjoyable and secure strategies that encourage PA participation among persons with dementia; spreading education opportunities for sports trainers to develop skills that will guarantee that sports clubs promote the inclusion of people with dementia in PA initiatives.ConclusionThe CFIR framework has the potential to support and facilitate implementation of long‐term PA projects for PwD by making it possible to address factors affecting their success.
References1. Nuzum, H., et al., Potential Benefits of Physical Activity in MCI and Dementia. Behav Neurol, 2020. 2020: p. 7807856.2. Hartman, Y.A.W., et al., Dementia Patients Are More Sedentary and Less Physically Active than Age‐ and Sex‐Matched Cognitively Healthy Older Adults. Dement Geriatr Cogn Disord, 2018. 46(1‐2): p. 81‐89.
Amyloid‐Beta and Cerebrovascular Disease Pathology Influence White Matter Microstructure and Executive Function in a Community‐Based Pre‐Dementia Asian Cohort
Authors: Vipin Ashwati , Soo See Ann , Kumar Dilip , Sandhu Gurveen Kaur , Zailan Fatin Zahra , Leow Yi Jin , Kandiah Nagaendran 
Published: December 2023

AbstractBackgroundWhite matter(WM) fibres have been shown to be vulnerable to amyloid‐beta and cerebrovascular disease(CVD) (Vipin et al.,2019; Croall et al.,2017; Salthouse et al.,2011). Indeed, fractional anisotropy(FA) of corpus callosum genu has been shown to capture variability in systemic vascular health and CVD (Vemuri et al., 2018). WM alterations are also associated with memory and executive function decline(Salthouse 2011). Additionally, the CAIDE risk score estimates future dementia risk based on vascular, demographic and genetic risk factors(Kivipelto et al.,2006). However, given the high CVD load among Asians, the combined influence of such risk factors and amyloid‐beta on WM microstructure and cognition in an Asian cohort needs further exploration. Thus, we examined WM FA between low, medium and high CVD‐amyloid pathology and association with cognition in a pre‐dementia Asian cohort. We hypothesized that derogatory WM FA reduction would be greatest in the high CVD‐amyloid group and relate to worse cognition.MethodIn a community cohort of 78 pre‐dementia subjects having undergone diffusion tensor imaging (mean age:55.37 years; mean education:14.72 years), neuropsychological assessments, CAIDE derivation (CVD risk) and oligomeric amyloid‐beta from the Dementia Research Centre (Singapore), we identified low CVD‐amyloid pathology (A‐C‐,n = 24), intermediate CVD‐amyloid (A±C±,n = 46) pathology and high CVD‐amyloid (A+C+,n = 8). TRActs Constrained by UnderLying Anatomy, FreeSurfer, was used to reconstruct major white matter tracts and fibre‐based FA, a measure of white matter tract overall health, was derived.ResultIncreasing CVD‐amyloid pathology related to worsening white matter microstructure with A+C+ subjects showing lowest FA in the corpus callosum genu compared to the A‐C‐ group (Fig. 1). Furthermore, higher FA in the corpus callosum splenium related to better executive function/ working memory performance (indexed using the digit span backwards test) in the A‐C‐ group (Fig. 2). In the A±C± group, presence of either amyloid or CVD pathology related to reduced executive function performance.ConclusionIn this community cohort of pre‐dementia older adults, we illustrate associations between presence of amyloid and CVD pathology and WM microstructure and cognitive disruption, especially in fibre tracts related to vascular disease and cognitive resilience. Early interventions targeting amyloid and vascular risk factors could encourage neuroplasticity, providing a window for recovery in cognitive performance.
Interactive associations between sleep properties and regional brain structure by race in midlife women
Authors: Paget‐Blanc Alexandra , Thurston Rebecca C , Schroeder Rachel A , Aizenstein Howard J , Derby Carol A. , Wu Minje , Chang Yuefang , Maki Pauline M 
Published: December 2023

AbstractBackgroundPoor sleep is a modifiable factor associated with increased risk of Alzheimer’s disease (AD). In cognitively normal adults, poor sleep is associated with AD‐like patterns of brain atrophy. Females experience greater age‐related deterioration in sleep quality than males, particularly around midlife, and these changes are more pronounced in racial/ethnic minority women than White women. Nevertheless, the association of sleep quality with brain health in midlife women, and race differences in this association is poorly understood. Here we examined the interactive associations of sleep and race on regional brain volume.MethodParticipants were cognitively normal women from the MsBrain cohort (n = 182; 59.16±4.23 years old; 99.0% postmenopausal; 88.5% White). Brain imaging was performed at the MR Research Center of the University of Pittsburgh on a 3T Siemens Tim Trio MR scanner. Freesurfer was used to segment and evaluate cortical thickness. Participants completed 72‐hour wrist actigraphy monitoring, which generated four sleep parameters: total sleep time (TST), wake after sleep onset (WASO), sleep fragmentation (SF) and sleep efficiency. The associations between sleep regional brain volume, and modification of these associations by race were evaluated using multiple linear regression adjusted for age, education, and presence of APOE 4 allele.ResultTST was inversely associated with cortical volume in the bilateral inferior parietal lobules (L: p<0.001; R: p<.01), superior parietal lobules (L: p<0.01; R: p<.05), precuneus (L:p<0.01; R: <.05), the left caudal anterior cingulate cortex (p<.05), and right parahippocampal cortex (p<.05). There was a significant interaction of SF and WASO and race on brain volume such that among Black women but not White women, higher SF and WASO were each associated with lower volume in bilateral orbitofrontal cortex (p<.05) and left cuneus (p<.01).ConclusionIn midlife women, longer sleep time and poorer sleep continuity may influence brain structure even in the absence of dementia. Results suggest that differences in the impact of sleep on brain health be explored further to understand race disparities in AD.. Understanding factors contributing to sleep degradation at midlife, particularly in Black women, may be a critical step to address gender and race disparities in AD.