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The Journal of Alzheimer’s Disease is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment and psychology of Alzheimer’s disease.
The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. The journal is dedicated to providing an open forum for original research that will expedite our fundamental understanding of Alzheimer’s disease.
Authors: Noori, Ayush | Jayakumar, Rojashree | Moturi, Vaishnavi | Li, Zhaozhi | Liu, Rongxin | Serrano-Pozo, Alberto | Hyman, Bradley T. | Das, Sudeshna
Article Type: Research Article
Abstract: Background: Recent Alzheimer’s disease (AD) discoveries are increasingly based on studies from a variety of omics technologies on large cohorts. Currently, there is no easily accessible resource for neuroscientists to browse, query, and visualize these complex datasets in a harmonized manner. Objective: Create an online portal of public omics datasets for AD research. Methods: We developed Alzheimer DataLENS, a web-based portal, using the R Shiny platform to query and visualize publicly available transcriptomics and genetics studies of AD on human cohorts. To ensure consistent representation of AD findings, all datasets were processed through a uniform bioinformatics …pipeline. Results: Alzheimer DataLENS currently houses 2 single-nucleus RNA sequencing datasets, over 30 bulk RNA sequencing datasets from 19 brain regions and 3 cohorts, and 2 genome-wide association studies (GWAS). Available visualizations for single-nucleus data include bubble plots, heatmaps, and UMAP plots; for bulk expression data include box plots and heatmaps; for pathways include protein-protein interaction network plots; and for GWAS results include Manhattan plots. Alzheimer DataLENS also links to two other knowledge resources: the AD Progression Atlas and the Astrocyte Atlas. Conclusions: Alzheimer DataLENS is a valuable resource for investigators to quickly and systematically explore omics datasets and is freely accessible at https://alzdatalens.partners.org . Show more
Keywords: Alzheimer’s disease, database, genetics, multiomics, single-cell RNA-seq, transcriptomics
DOI: 10.3233/JAD-230884
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2024
Authors: Wang, Yongchun | Jiang, Richeng | Li, Mingxi | Wang, Zicheng | Yang, Yu | Sun, Li
Article Type: Research Article
Abstract: Background: Alzheimer’s disease (AD) is the most common type of dementia, causing a huge socioeconomic burden. In parallel with the widespread uptake of single-cell RNA sequencing (scRNA-seq) technology, there has been a rapid accumulation of data produced by researching AD at single-cell resolution, which is more conductive to explore the neuroimmune-related mechanism of AD. Objective: To explore the potential features of T cells in the peripheral blood and cerebrospinal fluid of AD patients. Methods: Two datasets, GSE181279 and GSE134578, were integrated from GEO database. Seurat, Monocle, CellChat, scRepertoire, and singleR packages were mainly …employed for data analysis. Results: Our analysis demonstrated that in peripheral blood, T cells were significantly expanded, and these expanded T cells were possessed effector function, such as CD8+ TEMRA , CD4+ TEMRA , and CD8+ TEM . Interestingly, CD8+ TEMRA and CD4+ TEMRA cells positioned adjacently after dimensions reduction and clustering. Notably, we identified that the expanded T cells were developed from Naïve T cells and TCM cells, and TEM cells was in the intermediate state of this developing process. Additionally, in cerebrospinal fluid of AD patients, the amplified T cells were mainly CD8+ TEMRA cells, and the number and strength of communication between CD4+ TEM , CD8+ TEM , and CD8+ TEMRA were decreased in AD patients. Conclusions: Our comprehensive analyses identified the cells in cerebrospinal fluid from AD patients are expanded TEMRA or TEM cells and the TEMRA cells communicating with other immune cells is weakened, which may be an important immune feature that leads to AD. Show more
Keywords: Alzheimer’s disease, analysis of immune characteristics, immune cell subpopulation, single-cell RNA sequencing, TCR repertoire
DOI: 10.3233/JAD-230784
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-16, 2023
Authors: Snytnikova, Olga | Telegina, Darya | Savina, Ekaterina | Tsentalovich, Yuri | Kolosova, Nataliya
Article Type: Research Article
Abstract: Background: Alzheimer’s disease (AD) is the most common type of dementia in the elderly. Incomplete knowledge about the pathogenesis of this disease determines the absence of medications for the treatment of AD today. Animal models can provide the necessary knowledge to understand the mechanisms of biochemical processes occurring in the body in health and disease. Objective: To identify the most promising metabolomic predictors and biomarkers reflecting metabolic disorders in the development of AD signs. Methods: High resolution 1 H NMR spectroscopy was used for quantitative metabolomic profiling of the hippocampus of OXYS rats, an animal model …of sporadic AD, which demonstrates key characteristics of this disease. Animals were examined during several key periods: 20 days group corresponds to the “preclinical” period preceding the development of AD signs, during their manifestation (3 months), and active progression (18 months). Wistar rats of the same age were used as control. Results: Ranges of variation and mean concentrations were established for 59 brain metabolites. The main metabolic patterns during aging, which are involved in energy metabolism pathways and metabolic shifts of neurotransmitters, have been established. Of particular note is the significant increase of scyllo-inositol and decrease of hypotaurine in the hippocampus of OXYS rats as compared to Wistars for all studied age groups. Conclusions: We suggest that the accumulation of scyllo-inositol and the reduction of hypotaurine in the brain, even at an early age, can be considered as predictors and potential biomarkers of the development of AD signs in OXYS rats and, probably, in humans. Show more
Keywords: Aging, Alzheimer’s disease, hippocampal metabolome, hypotaurine, nuclear magnetic resonance spectroscopy, OXYS rats, scyllo-inositol
DOI: 10.3233/JAD-230706
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-18, 2023
Authors: Jehu, Deborah A. | Pottayil, Faheem | Dong, Yanbin | Zhu, Haidong | Sams, Richard | Young, Lufei
Article Type: Research Article
Abstract: Background: Physical activity preserves cognitive function in people without dementia, but the relationship between physical activity and cognitive domains among people living with dementia is unclear. Objective: The objective of this study was to explore the association between physical activity and cognition domains among people living with dementia. Methods: Participants living with dementia in residential care facilities (complete case analysis: n = 24/42) completed a battery of cognitive tests (global cognition : Montreal Cognitive Assessment; executive function : Trail-Making Test, Digit Span Forward Test; perception and orientation : Benton Judgement of Line Orientation Test; …language : Boston Naming Test; learning and memory : Rey Auditory Verbal Learning Test; complex attention : Digit Symbol Substitution Test). Participants wore an actigraphy monitor on their non-dominant wrist over seven days. We conducted a linear regression for total physical activity (independent variable) with race (white/black), fall risk (Morse Fall Scale), and the number of comorbidities (Functional Comorbidities Index) as covariates, and cognitive tests as variables of interest. Results: Participants were primarily male (75%), white (87.5%), and 50%had unspecified dementia (Alzheimer’s disease: 33%). Greater physical activity was associated with poorer global cognition, better executive function, and better learning and memory (p s < 0.05). Physical activity was not related to visuospatial perception, language, or complex attention. Conclusions: Physical activity may preserve executive function and learning and memory among people living with dementia. Wandering is more common in later stages of dementia, which may explain greater physical activity observed with lower global cognition. Regularly assessing physical activity may be useful in screening and monitoring cognitive changes. Show more
Keywords: Accelerometry, actigraphy, Alzheimer’s disease, cognition, cognitive domains, dementia, physical activity
DOI: 10.3233/JAD-230594
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2024
Authors: Gordon, Scott | Lee, Jong Soo | Scott, Tammy M. | Bhupathiraju, Shilpa | Ordovas, Jose | Kelly, Rachel S. | Tucker, Katherine L. | Palacios, Natalia
Article Type: Research Article
Abstract: Background: Recent studies have identified plasma metabolites associated with cognitive decline and Alzheimer’s disease; however, little research on this topic has been conducted in Latinos, especially Puerto Ricans. Objective: This study aims to add to the growing body of metabolomics research in Latinos to better understand and improve the health of this population. Methods: We assessed the association between plasma metabolites and global cognition over 12 years of follow-up in 736 participants of the Boston Puerto Rican Health Study (BPRHS). Metabolites were measured with untargeted metabolomic profiling (Metabolon, Inc) at baseline. We used covariable adjusted linear …mixed models (LMM) with a metabolite * time interaction term to identify metabolites (of 621 measured) associated with ∼12 years cognitive trajectory. Results: We observed strong inverse associations between medium-chain fatty acids, caproic acid, and the dicarboxylic acids, azelaic and sebacic acid, and global cognition. N-formylphenylalanine, a tyrosine pathway metabolite, was associated with improvement in cognitive trajectory. Conclusions: The metabolites identified in this study are generally consistent with prior literature and highlight a role medium chain fatty acid and tyrosine metabolism in cognitive decline. Show more
Keywords: Alzheimer’s disease, cognitive decline, Latinos, metabolomics, Puerto rican
DOI: 10.3233/JAD-230053
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2024
Authors: Beckers, Elise | Riphagen, Joost M. | Van Egroo, Maxime | Bennett, David A. | Jacobs, Heidi I.L.
Article Type: Short Communication
Abstract: Tau accumulation in and neurodegeneration of locus coeruleus (LC) neurons is observed in Alzheimer’s disease (AD). We investigated whether tangle and neuronal density in the rostral and caudal LC is characterized by an asymmetric pattern in 77 autopsy cases of the Rush Memory and Aging Project. We found left-right equivalence for tangle density across individuals with and without AD pathology. However, neuronal density, particularly in the caudal-rostral axis of the LC, is asymmetric among individuals with AD pathology. Asymmetry in LC neuronal density may signal advanced disease progression and should be considered in AD neuroimaging studies of LC neurodegeneration.
Keywords: Alzheimer’s disease, asymmetry, autopsy, brainstem, locus coeruleus, neurons, tangles
DOI: 10.3233/JAD-231328
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-7, 2024
Authors: Bini, Jason
Article Type: Article Commentary
Abstract: Excess cortisol is associated with more severe cognitive decline, Alzheimer’s disease, and related dementia phenotypes. The intracellular enzyme 11β-HSD1 regenerates active cortisol from inactive cortisone. In this current issue, high regional brain occupancy of Xanamemtrademark, determined by [11 C]TARACT PET imaging of 11β-HSD1, in cognitively normal individuals and mild cognitive impartment/Alzheimer’s disease (AD) patients is presented. In the future, comprehensive kinetic modeling using arterial sampling for occupancy studies, and whole-body PET imaging of 11β-HSD1 enzyme levels, in combination with stable isotope studies of cortisol metabolism, can provide broad insight into enzyme levels and activity in AD and other relevant diseases.
Keywords: Alzheimer’s disease, cortisol, positron emission tomography, 11β-hydroxysteroid dehydrogenase type 1
DOI: 10.3233/JAD-231463
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-3, 2024
Authors: Dorado-Martínez, Claudia | Montiel-Flores, Enrique | Ordoñez-Librado, Jose Luis | Gutierrez-Valdez, Ana Luisa | Garcia-Caballero, Cesar Alfonso | Sanchez-Betancourt, Javier | Reynoso-Erazo, Leonardo | Tron-Alvarez, Rocio | Rodríguez-Lara, Vianey | Avila-Costa, Maria Rosa
Article Type: Research Article
Abstract: Background: Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2 O5 ) causes cytoskeletal alterations suggesting that V2 O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer’s disease (AD)-like hippocampal cell death. Objective: This work aims to characterize an innovative AD experimental model through chronic V2 O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-β (Aβ) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. Methods: 20 male Wistar rats were divided into control …(deionized water) and experimental (0.02 M V2 O5 1 h, 3/week for 6 months) groups (n = 10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Results: Cognitive results in the T-maze showed memory impairment from the third month of V2 O5 inhalation. We also noted NFTs, Aβ plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. Conclusions: This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage. Show more
Keywords: Alzheimer’s disease experimental model, Aβ plaques, cell death, dendritic spine loss, inhaled exposure, neurofibrillary tangles, Vanadium pentoxide
DOI: 10.3233/JAD-230818
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-23, 2024
Authors: Das, Sudeshna
Article Type: Introduction
DOI: 10.3233/JAD-240272
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-3, 2024
Authors: Zhang, Zheting | Lim, Mervyn Jun Rui
Article Type: Review Article
Abstract: Post-stroke cognitive impairment and dementia (PSCID) is a complication that affects long-term functional outcomes after stroke. Studies on dementia after long-term follow-up in stroke have focused predominantly on ischemic stroke, which may be different from the development of dementia after spontaneous intracerebral hemorrhage (ICH). In this review, we summarize the existing data and hypotheses on the development of dementia after spontaneous ICH, review the management of post-ICH dementia, and suggest areas for future research. Dementia after spontaneous ICH has a cumulative incidence of up to 32.0–37.4% at 5 years post-ICH. Although the pathophysiology of post-ICH dementia has not been fully …understood, two main theoretical frameworks can be considered: 1) the triggering role of ICH (both primary and secondary brain injury) in precipitating cognitive decline and dementia; and 2) the contributory role of pre-existing brain pathology (including small vessel disease and neurodegenerative pathology), reduced cognitive reserve, and genetic factors predisposing to cognitive dysfunction. These pathophysiological pathways may have synergistic effects that converge on dysfunction of the neurovascular unit and disruptions in functional connectivity leading to dementia post-ICH. Management of post-ICH dementia may include screening and monitoring, cognitive therapy, and pharmacotherapy. Non-invasive brain stimulation is an emerging therapeutic modality under investigation for safety and efficacy. Our review highlights that there remains a paucity of data and standardized reporting on incident dementia after spontaneous ICH. Further research is imperative for determining the incidence, risk factors, and pathophysiology of post-ICH dementia, in order to identify new therapies for the treatment of this debilitating condition. Show more
Keywords: Alzheimer’s disease, cognitive dysfunction, dementia, hemorrhagic stroke, intracerebral hemorrhage, stroke
DOI: 10.3233/JAD-240111
Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2024
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