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Tourette Syndrome Research Highlights From 2024 [Version 3; Peer Review: 2 Approved, 1 Approved With Reservations], Andreas Hartmann, Per Andrén, Cyril Atkinson-Clement, Virginie Czernecki, Cécile Delorme, Simon Morand-Beaulieu, Nanette Mol Debes, Kirsten Müller-Vahl, Peristera Paschou, Natalia Szejko, Apostolia Topaloudi, Kevin J Black

2020-Current year OA Pubs

We summarize research reports from 2024 relevant to Tourette syndrome, which the authors consider the most important or interesting. This working draft aims to submit this content for publication around the beginning of 2025 in the yearly Tourette Syndrome Research Highlights series on F1000Research. The authors welcome article suggestions and thoughtful feedback from readers, who can add a comment by clicking on the rectangular comment box icon to the left of the LOG IN link at the top of this page. For private comments, you can reach us by email ( [email protected] or [email protected]).

Phase I Study Of Nt-I7, A Long-Acting Interleukin-7, In Severe Treatment-Related Lymphopenia Following Standard Radiation And Temozolomide For High-Grade Glioma, Jian L Campian, Milan G Chheda, John F Dipersio, Et Al.

2020-Current year OA Pubs

BACKGROUND: High-grade gliomas (HGG) have a poor prognosis despite aggressive treatment. Severe, persistent lymphopenia occurring in HGG patients after concurrent chemoradiation is associated with worse survival. NT-I7, a long-acting interleukin-7 analog, has been shown to increase CD4 and CD8 counts in healthy, septic, and HIV-positive adults. This multi-institutional, NCI-funded dose-escalation trial is the first to evaluate NT-I7 safety and activity in HGG patients with severe treatment-related lymphopenia (TRL) and the effect of co-administered glucocorticoids.

METHODS: Eligible HGG patients had CD4 counts < 300 cells/mm

RESULTS: NT-I7 was well tolerated in all 12 patients (median age 64; median CD4 count 161 cells/mm³) before the …

Recombinant Human Alpha-N-Acetylglucosamine-6-Sulfatase Delivered To Sanfilippo D Mice With Repeated Intracerebroventricular Injections Corrects Cns Pathology, Grant L. Austin, Feng Wang, Steven Q. Le, Alexander Sorensen, Shan Li, Lai C. Foong, Srikanth Singamsetty, Jill Wood, Tsui-Fen Chou, Patricia I. Dickson

2020-Current year OA Pubs

Mucopolysaccharidosis type IIID (MPS IIID; Sanfilippo D) is caused by biallelic pathogenic variants in N-acetylglucosamine-6-sulfatase (GNS), which participates in catabolism of heparan sulfate (HS) glycosaminoglycans. Characterization of MPS IIID disease at a cellular level has not been robustly achieved. We used unbiased quantitative proteomics to establish a cellular phenotype for MPS IIID mice. Recombinant human GNS (rhGNS), a variant of which previously demonstrated single dose efficacy in MPS IIID human fibroblasts and in MPS IIID neonatal mice, was used to establish a repeat dosing schedule to treat MPS IIID mice. Adult Gns KO mice or heterozygous carriers were treated via …

Wireless Modular Implantable Neural Device With One-Touch Magnetic Assembly For Versatile Neuromodulation, Inho Kang, John Bilbily, Choong Yeon Kim, Chuanqian Shi, Manish K Madasu, Eun Young Jeong, Kyle E Parker, Do A Kwon, Bum-Joon Jung, Jae-Soon Yang, Juhyun Lee, Noah D L Kabbaj, Wonhee Lee, Jun-Bo Yoon, Ream Al-Hasani, Jianliang Xiao, Jordan G Mccall, Jae-Woong Jeong

2020-Current year OA Pubs

Multimodal neural interfaces open new opportunities in brain research by enabling more sophisticated and systematic neural circuit dissection. Integrating complementary features across distinct functional domains, these multifunctional neural probes have greatly advanced the interrogation of complex neural circuitry. However, introducing multiple functionalities into a compact form factor for freely behaving animals presents substantial design hurdles that complicate the device or require more than one device. Moreover, fixed functionality poses challenges in meeting the dynamic needs of chronic neuroscience inquiry, such as replacing consumable parts like batteries or drugs. To address these limitations, the modular implantable neural device (MIND) is introduced …

Early Changes In Spatiotemporal Dynamics Of Remapped Circuits And Global Networks Predict Functional Recovery After Stroke In Mice, Ryan M Bowen, Jake Lee, Brendon Wang, Keith R Lohse, Hanyang Miao, Jonah A Padawer-Curry, Asher J Albertson, Eric C Landsness, Adam Q Bauer, Jin-Moo Lee

2020-Current year OA Pubs

SIGNIFICANCE: Stroke is the leading cause of chronic disability in the United States. How stroke size affects post-stroke repair and recovery is poorly understood.

AIM: We aim to investigate the effects of stroke size on early repair patterns and determine how early changes in neuronal circuits and networks predict functional outcomes after stroke.

APPROACH: We used wide-field optical imaging, photothrombosis, and the cylinder-rearing assay to examine changes in neuronal circuit and network activity in the context of functional recovery after stroke.

RESULTS: Larger strokes ablating

CONCLUSIONS: These results suggest that diffuse patterns of remapping, and desynchronization and hyperconnectivity of cortical …

Zika Virus Encephalitis Causes Transient Reduction Of Functional Cortical Connectivity, Shannon C Agner, Lindsey M Brier, Jeremy D Hill, Ethan Y Liu, Annie Bice, Rachel M Rahn, Shengxuan Chen, Joseph P Culver, Robyn S Klein

2020-Current year OA Pubs

SIGNIFICANCE: Determining the long-term cognitive impact of infections is clinically challenging. Using functional cortical connectivity, we demonstrate that interhemispheric cortical connectivity is decreased in individuals with acute Zika virus (ZIKV) encephalitis. This correlates with decreased presynaptic terminals in the somatosensory cortex. During recovery from ZIKV infection, presynaptic terminals recover, which is associated with recovered interhemispheric connectivity. This supports the contribution of synapses in the cortex to functional networks in the brain, which can be detected by widefield optical imaging. Although myeloid cell and astrocyte numbers are still increased during recovery, RNA transcription of multiple proinflammatory cytokines that increase during acute …

Endogenous Self-Peptides Guard Immune Privilege Of The Central Nervous System, Min Woo Kim, Wenqing Gao, Cheryl F Lichti, Xingxing Gu, Taitea Dykstra, Jay Cao, Igor Smirnov, Pavle Boskovic, Denis Kleverov, Andrea F M Salvador, Antoine Drieu, Kyungdeok Kim, Susan Blackburn, Clair Crewe, Maxim N Artyomov, Emil R Unanue, Jonathan Kipnis

2020-Current year OA Pubs

Despite the presence of strategically positioned anatomical barriers designed to protect the central nervous system (CNS), it is not entirely isolated from the immune system

Head-To-Head Preclinical Treatment Design Prioritizes Promising Therapies For Neurofibromatosis Type 1 Optic Glioma Clinical Translation, Talia Eligator, Jit Chatterjee, Shintaro Yamada, Anthony Kirchner, Hareesh B Nair, Jason R Fangusaro, David H Gutmann

2020-Current year OA Pubs

BACKGROUND: Authenticated preclinical brain tumor models provide unprecedented opportunities to evaluate next-generation treatments. However, some therapies with robust anti-tumor activity in mice fail in human trials, highlighting the need to better prioritize candidates for clinical translation. Herein, we implemented a head-to-head preclinical strategy using a well-characterized murine model of NF1-optic pathway glioma (

METHODS:

RESULTS: While all agents restored normal tissue architecture, reduced ON proliferation, and decreased TME soluble mediator and tumor cell marker RNA expression, only lamotrigine and mirdametinib also reduced ON volume. Everolimus, lamotrigine, and HBS-101 restored RNFL thickness to wild-type levels, whereas carboplatin showed a trend towards …

Piezo1-Mediated Calcium Influx Transiently Alters Nuclear Mechanical Properties Via Actin Remodeling In Chondrocytes, Jaquelin M Garcia-Castorena, Rosa Riester, Miranda Gamino-Ornelas, Nikitha Ada, Farshid Guilak, Marina Danalache

2020-Current year OA Pubs

Mechanosensation allows cells to generate intracellular signals in response to mechanical cues from their environment. Previous research has demonstrated that mechanical stress can alter the mechanical properties of the nucleus, affecting gene transcription, chromatin methylation, and nuclear mechanoprotection during mechanical loading. PIEZO1, a mechanically gated Ca

Alternative Approaches For Monitoring And Evaluation Of Lymphatic Filariasis Following Mass Drug Treatment With Ivermectin, Diethylcarbamazine And Albendazole In East New Britain Province, Papua New Guinea, Krufinta Bun, Benedict Mode, Melinda Susapu, Joyceline Salo, Catherine Bjerum, Michael Payne, Daniel Tisch, Makoto Sekihara, Emanuele Giorgi, Gary J. Weil, Peter U. Fischer, Leanne Robinson, Moses Laman, Christopher L. King

2020-Current year OA Pubs

BACKGROUND: WHO recommends two annual rounds of mass drug administration (MDA) with ivermectin, diethylcarbamazine, and albendazole (IDA) for lymphatic filariasis (LF) elimination in treatment naïve areas that are not co-endemic for onchocerciasis such as Papua New Guinea (PNG). Whether two rounds of MDA are necessary or sufficient and the optimal sampling strategies and endpoints for stopping MDA remain undefined.

METHODS AND FINDINGS: Two cross-sectional studies were conducted at baseline (N = 49 clusters or villages) and 12 months after mass drug administration (MDA) with IDA (N = 47 villages) to assess lymphatic filariasis (LF) by circulating filarial antigenemia (CFA) and …

Proteomic Characterization And Comparison Of The Infective And Adult Life Stage Secretomes From Necator Americanus And Ancylostoma Ceylanicum, Yide Wong, Bruce A. Rosa, Makedonka Mitreva, Et Al.

2020-Current year OA Pubs

More than 470 million people globally are infected with the hookworms Ancylostoma ceylanicum and Necator americanus, resulting in an annual loss of 2.1 to 4 million disability-adjusted-life-years. Current infection management approaches are limited by modest drug efficacy, the costs associated with frequent mass drug administration campaigns, and the risk of reinfection and burgeoning drug resistance. Subunit vaccines based on proteins excreted and secreted (ES) by hookworms that reduce worm numbers and associated disease burden are a promising management strategy to overcome these limitations. However, studies on the ES proteomes of hookworms have mainly described proteins from the adult life stage …

Cancer-Targeted Pro-Theranostic Bi-Metallic Organo-Coordination Nanoparticles, Hengbo Huang, Lei Fang, Janaka Wansapura, Julie L Prior, Brad Manion, Baogang Xu, Cody Hongsermeier, Nisha Gamadia, Nicole Blasi, Rui Tang, Christopher Egbulefu, Monica Shokeen, James D Quirk, Samuel Achilefu

2020-Current year OA Pubs

No abstract provided.

Structural Diversity Of Axonemes Across Mammalian Motile Cilia, Miguel Ricardo Leung, Chen Sun, Jianwei Zeng, Jacob R Anderson, Qingwei Niu, Wei Huang, Willem E M Noteborn, Alan Brown, Tzviya Zeev-Ben-Mordehai, Rui Zhang

2020-Current year OA Pubs

Reproduction, development and homeostasis depend on motile cilia, whose rhythmic beating is powered by a microtubule-based molecular machine called the axoneme. Although an atomic model of the axoneme is available for the alga Chlamydomonas reinhardtii

Slc35a2 Gene Product Modulates Paramyxovirus Fusion Events During Infection, Yanling Yang, Yuchen Wang, Danielle E. Campbell, Heng-Wei Lee, Wandy Beatty, Leran Wang, Megan Baldridge, Carolina B. López

2020-Current year OA Pubs

Paramyxoviruses are significant human and animal pathogens that include mumps virus (MuV), Newcastle disease virus (NDV) and the murine parainfluenza virus Sendai (SeV). Despite their importance, few host factors implicated in paramyxovirus infection are known. Using a recombinant SeV expressing destabilized eGFP (rSeVCdseGFP) in a loss-of-function CRISPR screen, we identified the CMP-sialic acid transporter (CST) gene SLC35A1 and the UDP-galactose transporter (UGT) gene SLC35A2 as essential for paramyxovirus infection. As expected, SLC35A1 knockout (KO) cells showed drastic reduction in infections with SeV, NDV and MuV due to the lack of cell surface sialic acids receptors. However, SLC35A2 KO cells revealed …

Molecular Regulation And Therapeutic Targeting Of Vldl Production In Cardiometabolic Disease, Kendall H Burks, Nathan O Stitziel, Nicholas O Davidson

2020-Current year OA Pubs

There exists a complex relationship between steatotic liver disease (SLD) and atherosclerotic cardiovascular disease (CVD). CVD is a leading cause of morbidity and mortality among individuals with SLD, particularly those with metabolic dysfunction-associated SLD (MASLD), a significant proportion of whom also exhibit features of insulin resistance. Recent evidence supports an expanded role of very low-density lipoprotein (VLDL) in the pathogenesis of CVD in patients, both with and without associated metabolic dysfunction. VLDL represents the major vehicle for exporting neutral lipid from hepatocytes, with each particle containing one molecule of apolipoproteinB100 (APOB100). VLDL production becomes dysregulated under conditions characteristic of MASLD …

Estimating Preclinical Amyloid Positivity: A Case Study Transporting Adni To Aric, Emma K Stapp, Elizabeth Rose Mayeda, Elizabeth A Stuart, Rebecca F Gottesman, Scott C Zimmerman, Dean F Wong, Thomas H Mosley, Michael E Griswold, M Maria Glymour, Melinda C Power, Alzheimer's Disease Neuroimaging Initiative

2020-Current year OA Pubs

INTRODUCTION: Alzheimer's disease and related dementias researchers have benefited from deeply phenotyped clinical samples; however, there is a critical need for estimates that generalize to diverse, representative populations. Use of a statistical approach from causal inference, "transport," may allow generalization of findings from clinical samples to other target populations. Here we explore the feasibility and validity of extending results from a clinical sample, the Alzheimer's Disease Neuroimaging Initiative (ADNI), to a community-based target sample, the Atherosclerosis Risk in Communities Study Positron Emission Tomography Amyloid Imaging Study (ARIC-PET) using transport estimation and a standard approach, direct standardization, which itself can be …

De Novo Lipid Synthesis In Cardiovascular Tissue And Disease, Tariq J Khan, Clay F Semenkovich, Mohamed A Zayed

2020-Current year OA Pubs

Most tissues have the capacity for endogenous lipid synthesis. A crucial foundational pathway for lipid synthesis is de novo lipid synthesis (DNL), a ubiquitous and complex metabolic process that occurs at high levels in the liver, adipose and brain tissue. Under normal physiological conditions, DNL is vital in converting excess carbohydrates into fatty acids. DNL is linked to other pathways, including the endogenous synthesis of phospholipids and sphingolipids. However, abnormal lipid synthesis can contribute to various pathologies and clinical conditions. Experimental studies involving dietary restriction and in vivo genetic modifications provide compelling evidence demonstrating the significance of lipid synthesis in …

Dfcp1 Is A Regulator Of Starvation-Driven Atgl-Mediated Lipid Droplet Lipolysis, Victoria A Ismail, Meg Schuetz, Zak N Baker, Jean A Castillo-Badillo, Teri V Naismith, David J Pagliarini, David J Kast

2020-Current year OA Pubs

Lipid droplets (LDs) are transient lipid storage organelles that can be readily tapped to resupply cells with energy or lipid building blocks, and therefore play a central role in cellular metabolism. Double FYVE Domain Containing Protein 1 (DFCP1/ZFYVE1) has emerged as a key regulator of LD metabolism, where the nucleotide-dependent accumulation of DFCP1 on LDs influences their size, number, and dynamics. Here we show that DFCP1 regulates lipid metabolism by directly modulating the activity of Adipose Triglyceride Lipase (ATGL/PNPLA2), the rate-limiting lipase driving the catabolism of LDs. We show through pharmacological inhibition of key enzymes associated with LD metabolism that …

Multisensory Naturalistic Decoding With High-Density Diffuse Optical Tomography, Kalyan Tripathy, Zachary E Markow, Morgan Fogarty, Mariel L Schroeder, Alexa M Svoboda, Adam T Eggebrecht, Bradley L Schlaggar, Jason W Trobaugh, Joseph P Culver

2020-Current year OA Pubs

SIGNIFICANCE: Decoding naturalistic content from brain activity has important neuroscience and clinical implications. Information about visual scenes and intelligible speech has been decoded from cortical activity using functional magnetic resonance imaging (fMRI) and electrocorticography, but widespread applications are limited by the logistics of these technologies.

AIM: High-density diffuse optical tomography (HD-DOT) offers image quality approaching that of fMRI but with the silent, open scanning environment afforded by optical methods, thus opening the door to more naturalistic research and applications. Although early visual decoding studies with HD-DOT have been promising, decoding of naturalistic auditory and multisensory stimulus information from HD-DOT data …

Rethinking Immune Check Point Inhibitors Use In Liver Transplantation: Implications And Resistance, Vivian Ortiz, Emilien Loeuillard

2020-Current year OA Pubs

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, including the two most common liver tumors, hepatocellular carcinoma and cholangiocarcinoma, but their use in the peri-transplantation period is controversial. ICI therapy aims to heighten cytotoxic T lymphocytes response against tumors. However, tumor recurrence is common owing to tumor immune response escape involving ablation of CTL response by interfering with antigen presentation, triggering CLT apoptosis and inducing epigenetic changes that promote ICI therapy resistance. ICI can also affect tissue resident memory T cell population, impact tolerance in the post-transplant period, and induce acute inflammation risking graft survival post-transplant. Their interaction with immunosuppression …

Schistosomiasis Interventions In Africa: Assessment And Systematic Review, Christopher Yaw Dumevi, George Boateng Kyei, Patience B Tetteh-Quarcoo, James-Paul Kretchy, Irene Ayi, Patrick F Ayeh-Kumi

2020-Current year OA Pubs

No abstract provided.

Protocol For The Asian Cohort For Alzheimer's Disease (Acad) Study, Pei-Chuan Ho, Walter A Kukull, Et Al.

2020-Current year OA Pubs

INTRODUCTION: To address knowledge gaps in Alzheimer's disease (AD) research, the Asian Cohort for Alzheimer's Disease (ACAD) Study will recruit over 5000 participants of Asian descent aged 60 or older in the United States and Canada. The current focus is on participants with Chinese, Korean, or Vietnamese ancestry, with the goal of characterizing both genetic and non-genetic risk factors. ACAD has assembled a culturally and linguistically appropriate data collection protocol, as well as a biosample collection protocol. Recruitment strategies follow community-based participatory research (CBPR) approaches to encourage research participation and engage Asian communities in brain health education.

METHODS: The ACAD …

Saponin Tql1055 Adjuvant-Containing Vaccine Confers Protection Upon Mycobacterium Tuberculosis Challenge In Mice, Mushtaq Ahmed, Eric Farris, Rosemary V Swanson, Shibali Das, Yan Yang, Tyler Martin, Shabaana A Khader

2020-Current year OA Pubs

Tuberculosis (TB), caused by the intracellular pathogen

Cochlear Mechanics Are Preserved After Inner Ear Delivery Of Gold Nanoparticles, Dorothy W Pan, Jinkyung Kim, Patricia M Quiñones, Anthony J Ricci, Brian E Applegate, John S Oghalai

2020-Current year OA Pubs

Novel therapeutic delivery systems and delivery methods to the inner ear are necessary to treat hearing loss and inner ear disorders. However, numerous barriers exist to therapeutic delivery into the bone-encased and immune-privileged environment of the inner ear and cochlea, which makes treating inner ear disorders challenging. Nanoparticles (NPs) are a type of therapeutic delivery system that can be engineered for multiple purposes, and posterior semicircular canal (PSCC) infusion is a method to directly deposit them into the cochlea. We sought to assess PSCC infusion of gold NPs into the cochlea, including the NPs' distribution and effect on cochlear mechanics. …

Loss Of Chop Prevents Joint Degeneration And Pain In A Mouse Model Of Pseudoachondroplasia, Jacqueline T Hecht, Alka C Veerisetty, Mohammad G Hossain, Debabrata Patra, Michele Carrer, Frankie Chiu, Dorde Relic, Paymaan Jafar-Nejad, Karen L Posey

2020-Current year OA Pubs

Pseudoachondroplasia (PSACH), a severe dwarfing condition characterized by impaired skeletal growth and early joint degeneration, results from mutations in cartilage oligomeric matrix protein (COMP). These mutations disrupt normal protein folding, leading to the accumulation of misfolded COMP in chondrocytes. The MT-COMP mouse is a murine model of PSACH that expresses D469del human COMP in response to doxycycline and replicates the PSACH chondrocyte and clinical pathology. The basis for the mutant-COMP pathology involves endoplasmic reticulum (ER) stress signaling through the PERK/eIF2α/CHOP pathway. C/EBP homologous protein (CHOP), in conjunction with a TNFα inflammatory process, upregulates mTORC1, hindering autophagy clearance of mutant COMP …

Regional Differences In Three-Dimensional Fiber Organization, Smooth Muscle Cell Phenotype, And Contractility In The Pregnant Mouse Cervix, Christopher J Hansen, Christine M O'Brien, Et Al.

2020-Current year OA Pubs

The orientation and function of smooth muscle in the cervix may contribute to the important biomechanical properties that change during pregnancy. Thus, this study examined the three-dimensional structure, smooth muscle phenotype, and mechanical and contractile functions of the upper and lower cervix of nongravid (not pregnant) and gravid (pregnant) mice. In gravid cervix, we uncovered region-specific changes in the structure and organization of fiber tracts. We also detected a greater proportion of contractile smooth muscle cells (SMCs), but an equal proportion of synthetic SMCs, in the upper versus lower cervix. Furthermore, we revealed that the lower cervix had infrequent spontaneous …

Protocol For A Non-Surgical Model Of Perineural Invasion For Assessing Neural Drivers Of Cancer Aggressiveness In Mice, Tiago H Zaninelli, Telma Saraiva-Santos, Brielle H Patlin, Michael Slade Stratton, David Y Chen, Felipe A Pinho-Ribeiro

2020-Current year OA Pubs

Perineural invasion (PNI) is a significant risk factor for cancer recurrence and metastasis; however, its mechanisms relating to cancer aggressiveness remain poorly understood. Here, we present a protocol for a non-surgical model of PNI in mice using a neurotropic melanoma cell line that migrates from the skin to the sciatic nerve. We describe the steps for cell culture and injection, tumor burden measurements, mouse euthanasia, and tissue dissection. We then detail procedures for sample cross-section and confocal imaging.

Bile Acids In Inflammatory Bowel Disease: From Pathophysiology To Treatment, Samantha H Bai, Arun Chandnani, Siyan Cao

2020-Current year OA Pubs

Inflammatory bowel disease (IBD) is a chronic condition that affects about 7 million people worldwide, and new therapies are needed. Understanding the complex roles that bile acids (BAs) play in IBD may lead to the development of novel IBD treatments independent of direct immunosuppression. This review discusses the latest discoveries in the roles BAs play in IBD pathogenesis and explores how these discoveries offer promising new therapeutic targets to treat IBD and improve patient outcomes. Several therapies discussed include specific BA receptor (BAR) agonists, dietary therapies, supplements, probiotics, and mesenchymal stem cell therapies that have all been shown to decrease …

Momordicine-I Suppresses Head And Neck Cancer Growth By Modulating Key Metabolic Pathways, Debojyoty Bandyopadhyay, Ellen T Tran, Ruchi A Patel, Matthew A Luetzen, Kevin Cho, Leah P Shriver, Gary J Patti, Mark A Varvares, David A Ford, Kyle S Mccommis, Ratna B Ray

2020-Current year OA Pubs

One of the hallmarks of cancer is metabolic reprogramming which controls cellular homeostasis and therapy resistance. Here, we investigated the effect of momordicine-I (M-I), a key bioactive compound from Momordica charantia (bitter melon), on metabolic pathways in human head and neck cancer (HNC) cells and a mouse HNC tumorigenicity model. We found that M-I treatment on HNC cells significantly reduced the expression of key glycolytic molecules, SLC2A1 (GLUT-1), HK1, PFKP, PDK3, PKM, and LDHA at the mRNA and protein levels. We further observed reduced lactate accumulation, suggesting glycolysis was perturbed in M-I treated HNC cells. Metabolomic analyses confirmed a marked …

Microglial Cd2ap Deficiency Exerts Protection In An Alzheimer's Disease Model Of Amyloidosis, Lingliang Zhang, David M. Holtzman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The CD2-associated protein (CD2AP) was initially identified in peripheral immune cells and regulates cytoskeleton and protein trafficking. Single nucleotide polymorphisms (SNPs) in the CD2AP gene have been associated with Alzheimer's disease (AD). However, the functional role of CD2AP, especially its role in microglia during AD onset, remains elusive.

METHODS: CD2AP protein levels in cultured primary cells and in 5xFAD mice was studied. Microglial CD2AP-deficient mice were crossed with 5xFAD mice and the offspring were subjected to neuropathological assessment, behavioral tests, electrophysiology, RNA-seq, Golgi staining, and biochemistry analysis. Primary microglia were also isolated for assessing their uptake and morphology changes. …