Digital Commons Network^™

Sequential Platinum And Parp Inhibition Enhances Pd1 Immunotherapy Efficacy In Murine Brca2 Mutated Pancreatic Cancer, John C Mcvey, Max M Wattenberg, Heather Coho, Kayjana Infante, Kelly Markowitz, Devora Delman, Cynthia Clendenin, Emma E Furth, Rashmi Tondon, Ben Z Stanger, Robert H Vonderheide, Kim A Reiss, Gregory L Beatty

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma (PDAC) is a challenging malignancy to treat, but emerging evidence suggests that specific subtypes may respond more favorably to certain therapies. BRCA-mutated PDAC represents a distinct subtype that is particularly sensitive to DNA-damaging therapies. The current standard of care for advanced BRCA-mutated PDAC involves induction platinum-based chemotherapy followed by maintenance therapy with a poly (ADP-ribose) polymerase inhibitor (PARPi). However, the randomized phase III POLO trial, upon which this standard is based, did not demonstrate an improved overall survival in patients who received olaparib compared to those who received placebo, highlighting the need for new therapeutic approaches. Additionally, …

A Heterogeneous Population Code At The First Synapse Of Vision, Tessa Herzog, Takeshi Yoshimatsu, Jose Moya-Diaz, Ben James, Leon Lagnado, Tom Baden

2020-Current year OA Pubs

Vision begins when photoreceptors convert fluctuations in light intensity into temporal patterns of glutamate release that drive the retinal network. The input-output relation at this first stage has not been studied in vivo so it is not known how it operates across a photoreceptor population. Using glutamate imaging in zebrafish, we find that individual type 1 cones (PR1; ancestral red cones), which dominate daylight vision in non-avian vertebrates, encode visual stimuli with high reliability and time-precision but routinely vary in sensitivity to luminance, contrast and frequency across the population. Variations in input-output relations are generated by feedback from the horizontal …

The Effects Of Ovine-Derived Reinforced Tissue Matrix Surrounding Silicone-Based Implants In A Rat Prepectoral Reconstruction Model, Sai L Pinni, Cameron Martin, Nicholas Fadell, Xiaochao Xia, Evan Marsh, Lauren Schellhardt, Xiaowei Li, Matthew D Wood, Justin M Sacks

2020-Current year OA Pubs

Silicone-based implants have been widely used in breast reconstruction but have also been associated with poorly understood complications, including pathologic foreign body responses such as capsular contracture. In this study, we leveraged 3D-printing technology to generate silicone-based implants in a novel, anatomically relevant, prepectoral rat model. We used this model to evaluate the response to an extracellular matrix-based product: ovine-derived reinforced tissue matrix (RTM). Two-piece negative molds were developed through computer-aided design and 3D-printed. The molds were filled with various polydimethylsiloxane mixtures and dip-coated to fabricate implants. Implant material characterization revealed that the implants retained the original 3D-printed mold shape …

Mast Cells Promote Pathology And Susceptibility In Tuberculosis, Ananya Gupta, Vibha Taneja, Javier Rangel-Moreno, Nilofer Naqvi, Abhimanyu, Yun Tao, Mushtaq Ahmed, Kuldeep Singh Chauhan, Daniela Trejo-Ponce De Leon, Gustavo Ramírez-Martínez, Luis Jiménez-Alvarez, Cesar Luna-Rivero, Joaquin Zuniga, Deepak Kaushal, Shabaana A Khader

2020-Current year OA Pubs

Tuberculosis (TB), caused by the bacterium

Ablation Of Cd38 In Multiple Myeloma Cells Leads To An Aggressive Phenotype In A Mouse Xenograft Model, Michael R Dyer, Alex Zheleznyak, Erin N Teubner, Julie L Prior, Brad Manion, Zhenghan Jing, Amit K Sharma, Junwei Du, Rui Tang, Mark A Fiala, John F Dipersio, Deborah Veis, Julie O'Neal, Mikhail Y Berezin, Monica Shokeen

2020-Current year OA Pubs

Multiple myeloma (MM) is a plasma cell malignancy characterized by bone pain and end-organ failure. A major challenge in treating MM is therapeutic resistance. CD38-targeted immunotherapies, such as daratumumab, have significantly improved outcomes; however, variable responses, resistance, and relapse remain vital challenges. We hypothesized that loss of CD38 drives a more aggressive phenotype and resistance to therapy. To test this, we developed a CD38 knockout (KO) clone of a human MM cell line and evaluated it in immunodeficient mice. Mice with CD38 KO tumors exhibited an increased tumor burden and reduced survival compared with those with CD38 wild-type (WT) tumors. …

Dual Roles Of Trpv2 In The Innate Immune Response To Cytosolic Dna: Arresting Dormant And Boosting Activated Sting, Chen Cheng, Hsiang-Ting Lu, Shan Li, Zhongsheng You

2020-Current year OA Pubs

The cGAS/STING-dependent innate immune pathway is central in the cellular response to cytosolic DNA derived from viral infections, genotoxic stress, or mitochondrial defects. While efficient activation of the pathway is crucial for defending against pathogens and cancer, maintaining its dormancy without stimuli is equally important to avoid autoimmunity. However, the precise control of the cGAS/STING pathway remains poorly understood. Here, we report that the ion channel TRPV2 regulates both the dormancy and activation of STING. TRPV2 associates with STING and suppresses spontaneous STING activation in the absence of cytoDNA but dissociates from STING and promotes its activation by releasing Ca

Distinct Contributions Of Etv2+ And Flk1+ Progenitors To Endothelial, Hematopoietic, And Cardiac Lineages, Dereck Alleyne, Minseo Kim, Jun Wu, Yoojung Kwon, Ye-Ram Kim, Ashraf Ul Kabir, Matthew Ishahak, Jeffrey R Millman, Changxu Fan, Hyung Joo Lee, Karen Krchma, Xiaoyun Xing, Kory Lavine, Ting Wang, Kyunghee Choi

2020-Current year OA Pubs

The ETS family transcription factor ETV2, VEGFA, and its receptor FLK1 are essential for hematopoietic, vascular, and cardiac development. Here, we combine dual Etv2 and Flk1 lineage tracing with molecular profiling to define how mesoderm progenitors are allocated to hematopoietic, endothelial, cardiomyocyte, and smooth muscle lineages. We demonstrate that hematopoietic, endothelial, and cardiac valves arise from dual Etv2

Myd88 Signaling In Myeloid Cells Induces Gastrointestinal Tract Injury And Systemic Inflammation After West Nile Virus Infection, Shih-Ching Lin, Fang R Zhao, Matthias Mack, Gabriel Mbalaviele, Michael S Diamond

2020-Current year OA Pubs

Humans with autoantibodies to type I interferons (IFNs) are at higher risk for neurological disease after West Nile virus (WNV) infection. IFN signaling deficient WNV-infected mice develop greater inflammation in the brain, which correlates with loss of gut barrier integrity. Here, we investigate the immune pathways that mediate this virus-gut-brain axis of inflammation. Myd88

Inducible Deletion Of Dgat1 And 2 From Microglia Exacerbates Neurodegeneration And Endolysosomal Lipid Accumulation In Male Ps19 Mice, G Travis Tabor, Alexandra Litvinchuk, Yun Chen, Austin Allison, Carisa Zeng, Hao Hu, Peter B Lin, Prabal Sharma, Samira Parhizkar, Sihui Song, Xin Bao, Abhirami K Iyer, Shih Feng You, Javier Remolina Serrano, Melissa Manis, Emily Franke, Anil G Cashikar, Carla M Yuede, Celeste M Karch, Eric J Huang, Maxim Artyomov, Jason D Ulrich, David M Holtzman, Et Al.

2020-Current year OA Pubs

Brain myeloid cells accumulate neutral lipids in multiple human neurodegenerative disorders and relevant mouse models. These lipids are often assumed to be contained in lipid droplets (LDs). While studies have been performed in cell culture and Drosophila models to characterize glial LDs, the roles of microglial LD biogenesis in mammalian tauopathy are unclear. To address this issue, we induced the deletion of diacylglycerol acyltransferases (DGATs) 1 and 2, enzymes critical for LD formation, from microglia in the PS19 mouse model of tauopathy. Microglial DGAT double knockout (KO) exacerbated neurodegeneration and increased the abundance of brain cholesteryl esters in male PS19 …

Creative Arts To Enhance Cervical Cancer Awareness Using Art-Based Messages From A Nigerian Crowdsourcing Open Call: Qualitative Thematic Analysis, Abdulhammed O Babatunde, Olufunto A Olusanya, Peter Kalulu, Temitope Ojo, Onyekachukwu Anikamadu, Juliet Iwelunmor, Et Al.

2020-Current year OA Pubs

BACKGROUND: Cervical cancer is a leading cause of cancer deaths among women in Nigeria, yet awareness is low. Historically, art has served as a medium for processing emotions and sharing experiences, which can be effective in promoting health and behavior change.

OBJECTIVE: This study aimed to examine art submissions and social media engagement from a Nigerian crowdsourcing open call to inform co-designed strategies for cervical cancer prevention among women.

METHODS: This study reported following the SRQR (Standard Reporting for Qualitative Research) guideline. From October to November 2023, we launched an open call for art on social media, inviting adult women …

Integrin Activation By Two Independently Regulated Calcium-Mediated Pathways Is Required For Neutrophil Recruitment, Marina Oguama, Pia Lindental, Regina A Clemens, Clifford A Lowell, Oliver Soehnlein, Johannes Roth, Tamam Bakchoul, Anika Cappenberg, Alexander Zarbock

2020-Current year OA Pubs

BACKGROUND: Impaired integrin activation on neutrophils is the hallmark of leukocyte adhesion deficiency syndrome in humans, characterized by reduced leukocyte recruitment. The regulation of intracellular calcium levels in neutrophils is important for cellular processes; however, the exact role of store-operated calcium entry (SOCE) and the involvement of stromal interaction molecule (STIM) calcium sensors, and ORAI1-3 calcium channels in neutrophil activation and recruitment is unknown.

METHODS: Using an acute kidney injury (AKI) model, intravital microscopy, and biochemical studies, we examined the molecular mechanisms of Ca

RESULTS: We demonstrate that STIM1 and ORAI1 in neutrophils are selectively required for E-selectin- and CXCL-1-, …

Induction Of Moderate Dna Damage Enhances Megakaryopoiesis And Platelet Production, Virginia Camacho, Luis Francisco Zirnberger Batista, Et Al.

2020-Current year OA Pubs

Megakaryocytes (MKs) are large, hematopoietic cells with a polyploid, multilobulated nucleus. Although DNA replication in MKs (endomitosis) is well studied, limited investigations have examined the impact of DNA instability on megakaryopoiesis. Poly-adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitors are chemotherapeutics that result in accumulation of DNA damage and are commonly associated with thrombocytopenia, presumably mediated through platelet progenitors, MKs. To explore PARP inhibitor-induced thrombocytopenia, we treated mice with the PARP inhibitor niraparib. Although high-dose niraparib treatment led to thrombocytopenia, consistent with clinical observations, lower-dose treatment led to a significant increase in bone marrow MKs, MK progenitors (MkPs), and circulating platelets. …

Differential Virulence And Immune Recognition Of Klebsiella Pneumoniae O-Antigen Subtypes O2Α And O2Β, Paeton L Wantuch, Lloyd S Robinson, Cory J Knoot, Christian M Harding, David A Rosen

2020-Current year OA Pubs

No abstract provided.

A Chemogenetic Approach For Temporal And Cell-Specific Activation Of Endogenous Gpcrs In Vivo, Gwendolyn Shingles, Qianqian Pang, Jian Weng, Ryan Singer, Waleed Babar, Jiaqi Shen, Luis Vazquez-Rivera, Yao Chen, Peng Li, Wenjing Wang

2020-Current year OA Pubs

Cell-specific regulation of endogenous G protein-coupled receptors (GPCRs) is crucial for understanding their roles in physiological processes. We present chemogenetic tools using shield-1-dependent irreversible protein switches to regulate peptide agonist activity. To demonstrate this platform, we engineered chemogenetically regulated pituitary adenylate cyclase activating polypeptide (cPACAP), which exhibited >15-fold chemical-dependent regulation of endogenous receptor activity. In vivo application of cPACAP allowed neuronal activation via the endogenous receptor for PACAP, engaging neural circuits that control respiratory and feeding behaviors. By integrating cPACAP with transgenic mice, we selectively activated endogenous PACAP receptor signaling in hypocretin-expressing neurons of the lateral hypothalamic area (LHA), revealing …

The Computationally Designed Tri2-2 Miniprotein Inhibitor Protects Against Multiple Sars-Cov-2 Omicron Variants, Jimin Lee, James Brett Case, Young-Jun Park, Rashmi Ravichandran, Daniel Asarnow, M Alejandra Tortorici, Jack T Brown, Shilpa Sanapala, Lauren Carter, David Baker, Michael S Diamond, David Veesler

2020-Current year OA Pubs

The continued evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has compromised neutralizing antibody responses elicited by prior infection or vaccination and abolished the utility of most monoclonal antibody therapeutics. We previously described a computationally-designed, homotrimeric miniprotein inhibitor, designated TRI2-2, that protects mice against pre-Omicron SARS-CoV-2 variants. Here, we show that TRI2-2 exhibits broadly neutralizing activity of SARS-CoV-2 variants and protects mice against BQ.1.1, XBB.1.5 and BA.2.86 challenge when administered intranasally post-exposure. The resistance of TRI2-2 to viral escape by most variants and the ability to deliver it directly to the upper airways highlight the potential of the multivalent …

Daily Locomotor Activity Declines With Tumor Growth And Disease Progression In Glioblastoma, Maria F Gonzalez-Aponte, Sofia V Salvatore, Anna R. Damato, Ruth Gn Katumba, Grayson R. Talcott, Omar H. Butt, Jian L. Campian, Jingqin Luo, Joshua B. Rubin, Olivia J. Walch, Erik D. Herzog

2020-Current year OA Pubs

Glioblastoma (GBM) is an aggressive brain tumor that often progresses despite resection and treatment. Timely and continuous assessment of GBM progression is critical to expedite secondary surgery or enrollment in clinical trials. However, current progression detection requires costly and specialized MRI examinations, which, in the absence of new symptoms or signs, are usually scheduled every 2-3 months. Here, we hypothesized that changes in daily activity are associated with GBM growth and disease progression. We found that wheel-running activity in GBM-bearing mice declined as tumors grew and preceded weight loss and circadian breakdown by over a week. Temozolomide treatment in the …

Renal Piezo2 Is An Essential Regulator Of Renin, Rose Z Hill, Jeffrey H Miner, Et Al.

2020-Current year OA Pubs

Renin synthesis and release is the rate-limiting step of the renin-angiotensin-aldosterone system (RAAS) that controls fluid homeostasis. A major activator of the RAAS is a decrease in perfusion pressure within the kidneys, suggesting a link between renal mechanotransduction and renin. However, the identity of the mechanosensor(s) in the kidneys and their physiological significance to the RAAS remain unclear. We find that loss of the force-gated nonselective cation channel PIEZO2 in cells of renin lineage dysregulates the RAAS by elevating renin. We observe that PIEZO2 is expressed in renin-producing juxtaglomerular granular cells and is required for their calcium dynamics in vivo. …

Characterization Of Novel Sigma Receptor Ligands Derived From Multicomponent Reactions As Efficacious Treatments For Neuropathic Pain, Ryosuke Shinouchi, Bengisu Turgutalp, Rohini S Ople, Shainnel O Eans, Ashai K Williams, Haylee R Hammond, Andras Varadi, Rebecca Notis Dardashti, Susruta Majumdar, Jay P Mclaughlin

2020-Current year OA Pubs

No abstract provided.

Antecedent Enhancer Activity Predicts Future Susceptibility To Seizures In Mice, Benjamin D Boros, Mariam A Gachechiladze, Juanru Guo, Dylan A Galloway, Shayna M Mueller, Mark Shabsovich, Allen Yen, Xuhua Chen, Alexander J Cammack, Tao Shen, Robi D Mitra, Joseph D Dougherty, Timothy M Miller

2020-Current year OA Pubs

Wide variation of responses to identical stimuli presented to genetically inbred mice suggests the hypothesis that stochastic non-genetic variation, such as in chromatin state or enhancer activity during neurodevelopment, can mediate such phenotypic differences. However, this hypothesis is largely untested since capturing pre-existing molecular states requires non-destructive, longitudinal recording. Therefore, we tested the potential of Calling Cards (CC) to record transient neuronal enhancer activity during postnatal development in mice, and thereby associate such non-genetic variation with a subsequent phenotypic presentation - degree of seizure response to the pro-convulsant pentylenetetrazol. We show that recorded differences in enhancer activity at 243 loci …

Neuronal Subtype Governs Amyloid Structure, Cellular Response, And Cognitive Outcome In Genetically Targeted App Mouse Models, Gabriella A Perez, Zoe Lai, George A Edwards Iii, Jacob M Dundee, Shannon N Leahy, Chuangye Qi, Yanyan Qi, Ye-Jin Park, Tzu-Chiao Lu, M Danish Uddin, Rong Zhao, Hui Zheng, Hongjie Li, Joanna L Jankowsky

2020-Current year OA Pubs

Pathological heterogeneity is increasingly appreciated in Alzheimer’s disease, yet we do not know how distinct aggregate conformations arise or influence cognitive outcomes. In an amyloid mouse model, we found that different brain regions formed structurally distinct Aβ deposits, prompting us to test whether neuronal subtypes shape aggregate conformation. To address this, we created transgenic mice expressing the same APP construct in either glutamatergic or GABAergic neurons. APP expression in GABAergic neurons resulted in diffuse plaques with high Aβ42/Aβ40 ratios and minimal gliosis, while glutamatergic expression produced neuritic plaques with activated glia. Despite similar Aβ levels, only mice with neuritic plaques …

Towards A Unified Gating Scheme For The Cnbd Ion Channel Family, Jenna L Lin, Baron Chanda

2020-Current year OA Pubs

Cyclic nucleotide-binding domain (CNBD) channels are critical components of numerous bioelectrical processes, including cardiac pacemaking, neuronal signaling, phototransduction in the eye, and stomatal regulation in plants. While members of this channel family share a conserved overall structure, they exhibit striking differences in voltage sensitivity. Hyperpolarization-activated cyclic nucleotide-gated channels are activated by membrane hyperpolarization, whereas ether-à-go-go channels open upon depolarization. Mutagenesis and chimeragenesis studies have revealed that some mutants display bipolar gating behavior-remaining closed at intermediate membrane potentials but capable of opening in response to both hyperpolarization and depolarization. Remarkably, in certain cases, just a few mutations are sufficient to reverse …

Β2 And Β3a Regulatory Subunits Can Coassemble In The Same Bk Channels, Yu Zhou, Vivian Gonzalez-Perez, Xiao-Ming Xia, Gopal S Kallure, Sandipan Chowdhury, Christopher J Lingle

2020-Current year OA Pubs

Ca2+- and voltage-activated BK-type K+ channels are influenced profoundly by associated regulatory subunits, including β subunits (Kcnmb1-4; β1-β4). Although overlap in expression of different BK β subunits occurs in native tissues, whether they can coassemble in the same channel complex is not known. We coexpress β2 and β3a subunits together with BK α and, through a combination of macroscopic and single-channel recordings, along with quantitative pull-down of tagged subunits, test whether coassembly can occur. We evaluate two models: (1) random mixing in which β2 and β3a subunits coassemble in the same channels, and (2) segregation in which β2 and β3a …

Impaired Complement Regulation Drives Chronic Lung Allograft Dysfunction After Lung Transplantation, Hrishikesh S. Kulkarni, Laneshia K. Tague, Fuyi Liao, Zhiyi Liu, Lorena Garnica, Nishanth R. Shankar, Xiaobo Wu, Dequan Zhou, Yan Tao, Victoria E. Davis, Cory T. Bernardt, Derek E. Byers, Chad A. Witt, Daniel Kreisel, John P. Atkinson, Andrew E. Gelman, Et Al.

2020-Current year OA Pubs

A greater understanding of chronic lung allograft dysfunction (CLAD) pathobiology, the primary cause of death after lung transplantation (LTx), is needed to improve outcomes. The complement system links innate to adaptive immune responses and is activated early after lung transplantation to form C3 convertase, a critical enzyme that cleaves the central complement component C3. We hypothesized that LTx recipients with a genetic predisposition to enhanced complement activation have worse CLAD-free survival mediated through increased adaptive alloimmunity. We interrogated a known functional C3 polymorphism (C3 R102G) that increases complement activation through impaired C3 convertase inactivation in 2 independent LTx recipient cohorts. …

Mouse Alport Podocytes Are Susceptible To Aav9 Transduction In Vivo, Meei-Hua Lin, Kohei Omachi, Joshua F Begin, Jennifer L Richardson, Jeffrey H Miner

2020-Current year OA Pubs

INTRODUCTION: Alport syndrome features a defective glomerular basement membrane (GBM) due to variants in COL4A3, COL4A4, and COL4A5. The most severe forms, which lack the GBM's collagen α3α4α5(IV) network, progress from hematuria in early childhood to proteinuria, chronic kidney disease, and kidney failure by the age of ∼30. As a monogenic disease without specific treatments, and with podocytes being the only glomerular cells that synthesize collagen α3α4α5(IV), the ability to efficiently deliver genes to Alport podocytes could open up new possibilities for treatment.

METHODS: As a proof-of-concept study, we investigated whether podocytes in X-linked Alport mice were susceptible to transduction …

Cgrp Expression And Signaling Sensitization In A Mouse Model Of Chronic Oxaliplatin-Induced Peripheral Neuropathy, Junwei Du, Leland C Sudlow, Margaret H Johnson, Kanishk Satish, Abraham Villagomez, Hongzhen Hu, Mikhail Y Berezin

2020-Current year OA Pubs

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and dose-limiting side effect of oxaliplatin treatment, yet its molecular mechanisms remain incompletely understood. Calcitonin gene-related peptide alpha (CGRPα, encoded by

Mapping Functional Connectivity In The Pigeon Brain With Wide-Field Optical Imaging, Kathryn C Chenard, Annie R Bice, Seana H Bice, Joseph P Culver, Paula Gerliz, Xavier Helluy, Onur Güntürkün, Jason W Trobaugh, Mehdi Behroozi, Carlos A Botero

2020-Current year OA Pubs

SIGNIFICANCE: Adapting optical imaging technology to avian models can overcome many limitations imposed by functional magnetic resonance imaging (fMRI), which currently restricts the number of species used to study functional connectivity. Developing advanced technology to expand the diversity of species that can be effectively imaged is crucial for addressing significant questions that are currently unreachable, such as understanding the evolution of cognition from a comparative perspective.

AIM: We assessed the potential of optical imaging technology to measure functional connectivity in birds, utilizing pigeons as an avian model. We evaluated whether we could partition the dorsal surface of the pigeon brain …

Immortalization And Characterization Of Schwann Cell Lines Derived From Nf1-Associated Cutaneous Neurofibromas, Hua Li, Angela Hirbe, Et Al.

2020-Current year OA Pubs

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition in which patients are heterozygous for a disruptive pathogenic variant in the NF1 gene. The most characteristic feature of the condition NF1 is the neurofibroma, a benign, multi-cellular tumor which initiates when a cell of the Schwann cell lineage gains a somatic pathogenic variant of the other NF1 allele. Neurofibromas developing at nerve termini in the skin are termed "cutaneous" neurofibromas (cNFs), while those developing within larger nerves are termed "plexiform." Most patients develop cNFs beginning in late childhood or early adulthood, continuing throughout life at variable rates. Some patients may …

Reliability Of Remote Self-Administered Web-Based Digital Cognitive Measures And Comparison To In-Person Neuropsychological Tests: Stricker Learning Span, Symbols Test, And The Mayo Test Drive Screening Battery Composite, Morgan A Hughes, Jason Hassenstab, Et Al.

2020-Current year OA Pubs

INTRODUCTION: We describe the reliability of remote self-administered digital cognitive measures completed via the Mayo Test Drive (MTD) web-based platform.

METHODS: A total of 1846 participants (mean age = 70, SD = 12, range 31-101; 48% male; 96% White; 99% non-Hispanic; 97% cognitively unimpaired) with two to four complete MTD sessions at ∼7.5-month intervals were included. Test-retest reliability was assessed using single-rating, absolute-agreement, and two-way mixed intraclass correlation coefficients (ICCs) with 95% confidence intervals. ICCs for in-person-administered traditional neuropsychological measures were compared to MTD for a subset of 244 participants. Analyses also compared reliability across demographic, residential, and session context …

The Association Between Major Depressive Disorder, Plasma Biomarkers Of Alzheimer's Disease, And Mild Behavioral Impairment Among Older Adults, Yiqi Zhu, Jean-Francois Trani, Ramkrishna K Singh, Semere Bekena, Jonathan Williams, Eric J Lenze, Ganesh M Babulal

2020-Current year OA Pubs

INTRODUCTION: Plasma biomarkers and mild behavioral impairment (MBI) are associated with dementia risk, but their relationships with major depressive disorder (MDD) are understudied. This study aimed to examine associations between plasma biomarkers of Alzheimer's disease (AD) and MBI among older adults with and without MDD.

METHODS: Older adults aged ≥65 were recruited from longitudinal studies of depression and AD (

RESULTS: Older adults with MDD were more likely to endorse MBI. After adjustment, Aβ42/Aβ40 and p-tau217/np-tau217 positivity were associated with MBI among those with MDD but not among those without.

DISCUSSION: Neuropsychatric symptoms (NPS) and biomarkers are AD risk factors. …

Antihypertensive Medications And Risk Of Alzheimer's Disease: Evidence For Specific Medication Use, Osvaldo J. Laurido-Soto, Alejandra Camacho-Soto, Irene M. Faust, Kassu M. Beyene, Aaron Katz, Jordan A. Killion, Brad A. Racette

2020-Current year OA Pubs

No abstract provided.