Biology subjects

Tian, H.

Publications and source records attributed to Tian, H..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

Reference mouse strain assemblies for BALB/c Nude and NOD/SCID mouse models

Mouse xenograft models play a vital role in tumor studies for research as well as for screening of drugs for the pharmaceutical industry. In particular, models with compromised immunity are favorable to increase the success of transplantation, such as e.g. NOD/SCID and BALB/c Nude strains. The genomic sequence and alterations of many of these models still remain elusive and might hamper a models further optimization or proper adapted usage. This can be in respect to treatments (e.g. NOD/SCID sensitivity to radiation), experiments or analysis of derived sequencing data of such models. Here we present the genome assemblies for the NOD/SCID and BALB/c nude strains to overcome this short-coming for the future and improve our understanding of these models in the process. We highlight as well first insights into observed genomic differences for these models compared to the C57BL/6 reference genome. Genome assemblies for both are close to full chromosome representations and provided with liftover annotations from the GRCm39 reference genome.

genomics↗

bioRxiv2023

Nutrient-regulated dynamics of chondroprogenitors in the postnatal murine growth plate

Longitudinal bone growth relies on endochondral ossification in the cartilaginous growth plate where chondrocytes accumulate and synthesize the matrix scaffold that is replaced by bone. The chondroprogenitors in the resting zone maintain the continuous turnover of chondrocytes in the growth plate. Malnutrition is a leading cause of growth retardation in children; however, after recovery from nutrient deprivation, bone growth is accelerated beyond the normal rate, a phenomenon termed catch-up growth. Though nutritional status is a known regulator of long bone growth, it is largely unknown if and how chondroprogenitor cells respond to deviations in nutrient availability. Here, using fate-mapping analysis in Axin2CreERT2 mice, we showed that dietary restriction increased the number of Axin2+ chondroprogenitors in the resting zone and simultaneously inhibited their differentiation. Once nutrient deficiency was resolved, the accumulated chondroprogenitor cells immediately restarted differentiation and formed chondrocyte columns, contributing to accelerated growth. Furthermore, we showed that nutrient deprivation reduced the level of phosphorylated Akt in the resting zone, and that exogenous IGF-1 canceled this reduction and stimulated differentiation of the pooled chondroprogenitors, decreasing their numbers. Our study of Axin2CreERT2 revealed that nutrient availability regulates the balance between accumulation and differentiation of chondroprogenitors in the growth plate, and further demonstrated that IGF-1 partially mediates this regulation by promoting the committed differentiation of the chondroprogenitor cells.

developmental biology↗

bioRxiv2023

Single-cell sequencing for the molecular identity involved in zinc therapy for spinal cord injury

Spinal cord injury (SCI) is a severe traumatic neurological condition often caused by car accidents, violent impacts, or unintentional falls and can have devastating consequences for the patient. SCI include primary and secondary injuries. Followed by primary injury, and secondary injuries including inflammatory responses and oxidative stress, which exacerbate the disease process of SCI. Therefore, the treatment of SCI, especially the suppression of secondary injuries, is a major focus of attention in the field of neuroscience. In previous studies, we have demonstrated that zinc therapy can exert neuroprotective effects in mice after acute SCI, including reducing the inflammatory response in the central nervous system, decreasing the neuronal apoptosis and downregulating oxidative stress at the region of injury. However, little is known about how zinc therapy systematically alleviates SCI. Here, we have systematically analysed and mapped the single-cell atlas of the spinal cord in mice with SCI treated by zinc therapy, which provides a systematic analysis of the transcriptome of individual cells in the spinal cord. Among the results, we found that zinc therapy-induced alterations in the IL-17 inflammatory pathway and produced immune heterogeneity in microglia which are the inherent immune cells in the central nervous system. By cell subpopulations clustering analysis, we defined seven microglia subpopulations in zinc-therapy spinal cord tissue and identified the presence of novel VEGFA+ microglia. This finding presents that the microglia subpopulations affected by zinc therapy may have the potential to promote angiogenesis, which is a potential mechanism for the treatment of SCI. In conclusion, this study maps/reveals the transcriptomic of zinc therapy for the treatment of acute SCI with unprecedented resolution and provides a molecular basis for the clinical application.

genomics↗

bioRxiv2023

Prion-like characteristics of Hepatitis E virus ORF3 protein are associated with virus release and pathogenesis

Hepatitis E virus (HEV) is a common causative agent of acute hepatitis. Due to the shortage of efficient in vitro model, the viral assembly and release processes are still poorly understood. In this study, we found that ORF3, an HEV structural protein showed prion-like properties. The prion domain (PrD) of yeast prion Sup35 could be functionally replaced by HEV-ORF3 and its candidate PrD (cPrD). A single amino acid substitution in the cPrD reduced the aggregation propensity of ORF3 and blocked the function of ORF3 in enhancing the stability of microtubules in HEV-infected cells, thus blocking virion release from the infected cells and resulting in reduced HEV pathogenicity in Mongolian gerbils. These data suggest that HEV-ORF3 is a novel functional prion-like protein which assembles into a filamentous structure for virion release, supporting the hypothesis that the self-propagating properties of prion proteins are widely exploited as epigenetic information carriers in nature.

microbiology↗

bioRxiv2022

Probing Conformational Landscapes and Mechanisms of Allosteric Communication in the Functional States of the ABL Kinase Domain Using Multiscale Simulations and Network-Based Mutational Profiling of Allosteric Residue Potentials

In the current study, multiscale simulation approaches and dynamic network methods are employed to examine the dynamic and energetic details of conformational landscapes and allosteric interactions in the ABL kinase domain that determine the kinase functions. Using a plethora of synergistic computational approaches, we elucidate how conformational transitions between the active and inactive ABL states can employ allosteric regulatory switches to modulate the intramolecular communication networks between the ATP site, the substrate binding region, and the allosteric binding pocket. A perturbation-based network approach that implements mutational profiling of allosteric residue propensities and communications in the ABL states is proposed. Consistent with the biophysical experiments, the results reveal functionally significant shifts of the allosteric interaction networks in which preferential communication paths between the ATP binding site and substrate regions in the active ABL state become suppressed in the closed inactive ABL form, which in turn features favorable allosteric couplings between the ATP site and the allosteric binding pocket. By integrating the results of atomistic simulations with dimensionality reduction methods and Markov state models we analyze the mechanistic role of the macrostates and characterize kinetic transitions between the ABL conformational states. Using network-based mutational scanning of allosteric residue propensities, this study provides a comprehensive computational analysis of the long-range communications in the ABL kinase domain and identifies conserved regulatory hotspots that modulate kinase activity and allosteric cross-talk between the allosteric pocket, ATP binding site and substrate binding regions.

biophysics↗

bioRxiv2022

NR5A2 connects genome activation to the first lineage segregation in early mouse development

After fertilization, zygotic genome activation (ZGA) marks the beginning of the embryonic program for a totipotent embryo, which further gives rise to the pluripotent embryonic lineages and extraembryonic trophectoderm after the first lineage commitment. While much has been learned about pluripotency regulation, how ZGA is connected to the pluripotency commitment in early embryos remains elusive. Here, we investigated the role of nuclear receptor 1 family transcription factors (TFs) in mouse pre-implantation embryos, whose motifs are highly enriched in accessible chromatin at the 2-cell (2C) to 8-cell (8C) stages after ZGA. We found NR5A2, an NR TF highly induced upon ZGA, is required for early development, as both the knockdown and knockout of Nr5a2 from 1C embryos led to morula arrest. While the zygotic genome was largely activated at the 2C stage, 4-8C-specific gene activation (mid-preimplantation activation) was substantially impaired. Genome-wide chromatin binding and RNA-seq analyses showed NR5A2 preferentially regulates its binding targets including a subset of key pluripotency genes (i.e., Nanog, Pou5f1, and Tdgf1). Finally, NR5A2-occupied sites at the 2C and 8C stages predominantly reside in accessible B1 elements where its motif is embedded. Taken together, these data identify NR5A2 as a key regulator that connects ZGA to the first lineage segregation in early mouse development.

developmental biology↗

bioRxiv2022

Complexes Formed by Mixing Tumor-derived Extracellular Vesicles with Polymeric Surfactants for Personalized Therapeutic Vaccine

The personalized therapeutic vaccine is an ideal weapon to eliminate tumors. However, the core steps of manufacturing personalized cancer vaccines are identifying tumor-specific antigens (TSAs, also called neoantigens) and HLA epitope prediction, which is time-consuming and labor-intense. Tumor-derived extracellular vesicles (TEVs) are alternative sources of neoantigens. However, the immunosuppressive nature of TEVs limits their application in such immunotherapy. In this study, we present a new strategy to maintain neoantigens in TEVs and diminish the immunosuppression by deconstructing the structure of TEVs with polymeric surfactant polyethylene glycol-phosphatidylethanolamine (PEG-PE). Together with adjuvant MPLA, the newly formed micelle-like complexes compose a therapeutic vaccine (MLC-V). Results show that MLC-V is capable of eliciting neoantigen-specific T-cell responses, restoring TEV-induced immunosuppression, and preventing lung metastasis of murine melanoma. MLC-V also exhibits outstanding anti-tumor efficacy in multiple tumor models. MLC-V can be used as a personalized therapeutic vaccine in a mimetic pre-clinical MC38 model and the anti-tumor effect of MLC-V was synergistically enhanced by PD-1 mAb. Taken together, the present study demonstrates a time-saving, low-cost, and simplified strategy to produce personalized therapeutic vaccines based on MLC-V platform technology.

immunology↗

bioRxiv2022

Multimodal mass spectrometry imaging reveals single-cell metabolic states in mammalian liver

We have developed a powerful workflow to imaging endogenous metabolism in single cells on frozen tissue, allowing us to discover new cell subtypes in human liver. Performing spatially integrated multiomics in single cells within tissues is at the leading frontier in biology but has been prevented by technological challenges. We developed a critical new technology, cryogenic water cluster ion beam secondary ion mass spectrometry imaging ((H2O)n>28K-GCIB-SIMS)) at 1 {micro}m single-cell resolution. This allowed us to perform multi-modal mass spectrometry imaging (MSI) to detect metabolites, lipids, and proteins in single cells within functional liver zones and diverse cell types in the native tissue state. Our workflow utilizes the desorption electrospray ionization (DESI) mass spectrometry imaging (MSI) to build a reference map of metabolic heterogeneity and zonation across liver functional units. Then cryogenic (H2O)n>28K-GCIB-SIMS and C60-SIMS integrated metabolomics, lipidomic and proteomics, - characterizing the metabolic state in single cells on the same tissue section. We found for the first time that lipids and metabolites can classify liver metabolic zones and liver cell types beyond histological and protein-marker annotation. This provides a multi-modal workflow to define single-cell states in normal physiology and disease in mammalian tissue.

cell biology↗

bioRxiv2022

Relaxing parametric assumptions for non-linear Mendelian randomization using a doubly-ranked stratification method

Non-linear Mendelian randomization is an extension to standard Mendelian randomization to explore the shape of the causal relationship between an exposure and outcome using an instrumental variable. The approach divides the population into strata and calculates separate instrumental variable estimates in each stratum. However, the standard implementation of stratification in non-linear Mendelian randomization, referred to as the residual method, relies on strong parametric assumptions of linearity and homogeneity between the instrument and the exposure to form the strata. If these stratification assumptions are violated, the instrumental variable assumptions may be violated in the strata even if they are satisfied in the population, resulting in misleading estimates. We propose a new stratification method, referred to as the doubly-ranked method, that does not require strict parametric assumptions to create strata with different average levels of the exposure such that the instrumental variable assumptions are satisfied within the strata. Our simulation study indicates that the doubly-ranked method can obtain unbiased stratum-specific estimates and appropriate coverage rates even when the effect of the instrument on the exposure is non-linear or heterogeneous. Moreover, it can also provide unbiased estimates when the exposure is coarsened (that is, rounded, binned into categories, or truncated), a scenario that is common in applied practice and leads to substantial bias in the residual method. We applied the proposed doubly-ranked method to investigate the effect of alcohol intake on systolic blood pressure, and found evidence of a positive effect of alcohol intake, particularly at higher levels of alcohol consumption.

genetics↗

bioRxiv2022

Strong and consistent associations of waterbird community composition with HPAI H5 occurrence in European wild birds

Since 2014, highly pathogenic avian influenza (HPAI) H5 viruses of clade 2.3.4.4 have been dominating the outbreaks across Europe, causing massive deaths among poultry and wild birds. However, the factors shaping its broad-scale outbreak patterns remain unclear. With extensive waterbird survey datasets of about 7,000 sites across Europe, we here demonstrated that H5N8 occurrence in wild birds in the 2016/17 and 2020/21 epidemics as well as H5N1 occurrence in 2005/06 epidemic were strongly associated with very similar waterbird community attributes, pointing to the possibility of similar interspecific transmission processes between different epidemics. A simple extrapolation of the model constructed from the 2016/17 epidemic can well predict the H5N8 pattern in wild birds in 2020/21 epidemic. We also found a dilution effect of phylogenetic diversity that was always negatively correlated with H5 occurrence in wild birds. In contrast, H5N8 occurrence in poultry was subject to different risk factors between the two epidemics. In general, waterbird community composition play a much more important role in determining the spatial pattern of H5N8 in wild birds than in poultry. Our work contributes to reveal the factors driving H5N8 patterns, and highlights the value of waterbird community factors in future HPAI surveillance and prediction.

ecology↗

bioRxiv2022

Topological action potentials in engineered tissues

Due to the nonlinear current-voltage relations of ion channels, an interface between two tissues can have very different bioelectrical properties compared to either tissue on its own. Here we show experimentally that gap junction-coupled interfaces between non-excitable tissues can be electrically excitable. This topologically protected excitability occurs over a far larger range of ion channel expression levels than does excitability in the bulk. Topological excitations at tissue interfaces can cause local elevations in calcium concentration, possibly providing a bioelectrical mechanism for interface sensing. As in condensed matter physics, topological excitations in electrophysiology constitute a distinct class of phenomena which may show exotic and novel properties.

biophysics↗

bioRxiv2021

All-optical electrophysiology with improved genetically encoded voltage indicators reveals interneuron network dynamics in vivo

All-optical electrophysiology can be a powerful tool for studying neural dynamics in vivo, as it offers the ability to image and perturb membrane voltage in multiple cells simultaneously. The "Optopatch" constructs combine a red-shifted archaerhodopsin (Arch)-derived genetically encoded voltage indicator (GEVI) with a blue-shifted channelrhodopsin actuator (ChR). We used a video-based pooled screen to evolve Arch-derived GEVIs with improved signal-to-noise ratio (QuasAr6a) and kinetics (QuasAr6b). By combining optogenetic stimulation of individual cells with high-precision voltage imaging in neighboring cells, we mapped inhibitory and gap junction-mediated connections, in vivo. Optogenetic activation of a single NDNF-expressing neuron in visual cortex Layer 1 significantly suppressed the spike rate in some neighboring NDNF interneurons. Hippocampal PV cells showed near-synchronous spikes across multiple cells at a frequency significantly above what one would expect from independent spiking, suggesting that collective inhibitory spikes may play an important signaling role in vivo. By stimulating individual cells and recording from neighbors, we quantified gap junction coupling strengths. Together, these results demonstrate powerful new tools for all-optical microcircuit dissection in live mice.

neuroscience↗

bioRxiv2021

Understanding gene regulatory mechanisms based on gene classification

The CpG dinucleotide and its methylation play vital roles in gene regulation as well as 3D genome organization. Previous studies have divided genes into several categories based on the CpG intensity around transcription starting sites (TSS) and found that housekeeping genes tend to possess high CpG density while tissue-specific genes are generally characterized by low CpG density. In this study, we investigated how the CpG density distribution of a gene affects its transcription and regulation pattern. Based on the CpG density distribution around TSS, the human genes are clearly divided into different categories. Not only sequence properties, these different clusters exhibited distinctly different structural features, regulatory mechanisms, and correlation patterns between expression level and CpG/TpG density. These results emphasized that the usage of epigenetic marks in gene regulation is partially rooted in the sequence property of genes, such as their CpG density distribution.

genomics↗

bioRxiv2021

Ancient genomes redate the extinction of Sussemionus, a subgenus of Equus, to late Holocene

The exceptionally-rich fossil record available for the equid family has provided textbook examples of macroevolutionary changes. Horses, asses and zebras represent three extant subgenus of Equus lineage, while the Sussemionus subgenus is another remarkable Equus lineage ranging from North America to Ethiopia in Pleistocene. We sequenced 26 archaeological specimens from northern China in Holocene showing morphological features reminiscent of Equus ovodovi, a species representative of Sussemionus, and further confirmed them as this species by genetic analyses. Thus, we present the first high-quality complete genome of the Sussemionus that we sequenced to 12.0x depth-of-coverage and demonstrate that it survived until [~]3,500 years ago, despite the continued demographic collapse during the Last Glacial Maximum and the great human expansion in East Asia. We also confirmed the Equus phylogenetic tree, and found Sussemionus diverged from the ancestor of non-caballine equids [~]2.3-2.7 Million years ago and admixture events could have taken place between them. Our works suggest the small genetic diversity but not the enhanced inbreeding mainly limited the chances of survival of the species, and illustrates how ancient DNA can inform on extinction dynamics and the long-term resilience of species surviving in cryptic population pockets.

genomics↗

bioRxiv2021

Fanconi Anemia Pathway Deficiency Drives Copy Number Variation in Squamous Cell Carcinomas

Fanconi anemia (FA), a model syndrome of genome instability, is caused by a deficiency in DNA interstrand crosslink (ICL) repair resulting in chromosome breakage1-3. The FA repair pathway comprises at least 22 FANC proteins including BRCA1 and BRCA24-6, and protects against carcinogenic endogenous and exogenous aldehydes7-10. Individuals with FA are hundreds to thousands-fold more likely to develop head and neck (HNSCC), esophageal and anogenital squamous cell carcinomas (SCCs) with a median onset age of 31 years11. The aggressive nature of these tumors and poor patient tolerance of platinum and radiation-based therapy have been associated with short survival in FA11-16. Molecular studies of SCCs from individuals with FA (FA SCCs) have been limited, and it is unclear how they relate to sporadic HNSCCs primarily driven by tobacco and alcohol exposure or human papillomavirus (HPV) infection17. Here, by sequencing FA SCCs, we demonstrate that the primary genomic signature of FA-deficiency is the presence of a high number of structural variants (SVs). SVs are enriched for small deletions, unbalanced translocations, and fold-back inversions that arise in the context of TP53 loss. The SV breakpoints preferentially localize to early replicating regions, common fragile sites, tandem repeats, and SINE elements. SVs are often connected forming complex rearrangements. Resultant genomic instability underlies elevated copy number alteration (CNA) rates of key HNSCC-associated genes, including PIK3CA, MYC, CSMD1, PTPRD, YAP1, MXD4, and EGFR. In contrast to sporadic HNSCC, we find no evidence of HPV infection in FA HNSCC, although positive cases were identified in gynecologic tumors. A murine allograft model of FA pathway-deficient SCC was enriched in SVs, exhibited dramatic tumor growth advantage, more rapid epithelial-to-mesenchymal transition (EMT), and enhanced autonomous inflammatory signaling when compared to an FA pathway-proficient model. In light of the protective role of the FA pathway against SV formation uncovered here, and recent findings of FA pathway insufficiency in the setting of increased formaldehyde load resulting in hematopoietic stem cell failure and carcinogenesis18-20, we propose that high copy-number instability in sporadic HNSCC may result from functional overload of the FA pathway by endogenous and exogenous DNA crosslinking agents. Our work lays the foundation for improved FA patient treatment and demonstrates that FA SCC is a powerful model to study tumorigenesis resulting from DNA crosslinking damage.

cancer biology↗

bioRxiv2021

Kindlin-2 preserves integrity of the articular cartilage to protect against osteoarthritis

Osteoarthritis (OA) is an aging-related degenerative joint disease, which has no cure partly due to limited understanding of its pathological mechanism(s). Here we report that the focal adhesion protein Kindlin-2, but not Kindlin-1 or -3, is highly expressed in articular chondrocytes of the hyaline cartilage, which is dramatically decreased in the degenerated articular cartilage of aged mice and patients with OA. Inducible deletion of Kindlin-2 in chondrocytes at adult stage leads to spontaneous OA and much severe OA lesions in the mice receiving the surgery of destabilization of the medial meniscus. Mechanistically, Kindlin-2 deficiency promotes mitochondrial oxidative stress and activates Stat3 in articular chondrocytes, leading to Runx2-mediated chondrocyte hypertrophic differentiation and catabolism. In vivo, systemic pharmacological blockade of Stat3 activation or genetic ablation of Stat3 in chondrocytes reverses aberrant accumulation of Runx2 and ECM-degrading enzymes and limits OA deteriorations caused by Kindlin-2 deficiency. Furthermore, genetic inactivation of Runx2 in chondrocytes reverses structural changes and OA lesions caused by Kindlin-2 deletion without down-regulating p-Stat3 in articular chondrocytes. Of translational significance, intraarticular injection of Kindlin-2-expressing adeno-associated virus decelerates progression of aging- and instability-induced knee joint OA in mice. Collectively, we identify a novel pathway comprising of Kindlin-2, Stat3 and Runx2 in articular chondrocytes responsible for maintaining integrity of the articular cartilage and define a potential therapeutic target for OA.

pathology↗

bioRxiv2021

Dendro-somatic synaptic inputs to ganglion cells violate receptive field and connectivity rules in the mammalian retina

In retinal neurons, morphology strongly influences visual response features. Ganglion cell (GC) dendrites ramify in distinct strata of the inner plexiform layer (IPL) so that GCs responding to light increments (ON) or decrements (OFF) receive appropriate excitatory inputs. This vertical stratification prescribes response polarity and ensures consistent connectivity between cell types, whereas the lateral extent of GC dendritic arbors typically dictates receptive field (RF) size. Here, we identify circuitry in mouse retina that contradicts these conventions. A2 amacrine cells are interneurons understood to mediate "cross-over" inhibition by relaying excitatory input from the ON layer to inhibitory outputs in the OFF layer. Ultrastructural and physiological analyses show, however, that some A2s deliver powerful inhibition to OFF GC somas and proximal dendrites in the ON layer, rendering their inhibitory RFs smaller than their dendritic arbors. This OFF pathway, avoiding entirely the OFF region of the IPL, challenges several tenets of retinal circuitry.

neuroscience↗

bioRxiv2021

Competition between distinct ApoE alleles and mCRP for the endothelial receptor CD31 differentially regulates neurovascular inflammation and Alzheimer's disease pathology

BACKGROUNDC-reactive protein (CRP) in peripheral inflammation is associated with increased Alzheimers disease (AD) risk in Apolipoprotein E4 (ApoE4), but not ApoE3 or E2, humans. It remains unknown whether peripheral monomeric CRP (mCRP) induces AD pathogenesis through some receptor of blood-facing endothelia in the brain in an ApoE genotype dependent fashion. METHODSWe used human samples, ApoE knock-in and deficient mouse models, and primary brain endothelia. Different ApoE mice were intraperitoneally (i.p.) injected with mCRP. The characterizations by immunostaining, proximity ligation assay (PLA) and siRNA were conducted to identify the receptor for mCRP. Brain microvessel and endothelia were isolated for RNA sequencing to explore the molecular pathway. RESULTSWe demonstrate that CD31 (PECAM-1), a blood-facing endothelial receptor in brain, is a competitive target of both mCRP and ApoE protein. ApoE2 competes more strongly with mCRP for CD31 than ApoE4 does, and expressing ApoE4 or knocking out ApoE gene results in higher levels of mCRP-CD31 binding, leading to a decrease of CD31 expression but an increase in CD31 phosphorylation, along with greater cerebrovascular damage and AD pathology. This competitive binding mediates differential endothelial molecular responses depending on ApoE genotype, increasing cerebrovascular inflammation and mitochondria impairment in ApoE4 mice, while inducing vasculogenesis and protective changes in the presence of ApoE2. CONCLUSIONSOur study reveals a novel and dynamic endothelial ApoE-mCRP-CD31 pathway for AD pathogenesis during chronic inflammation and provides some insight into the opposing ApoE4-neurodegenerative and ApoE2-neuroprotective effects in AD. Clinical PerspectiveO_ST_ABSWHAT IS NEW?C_ST_ABSO_LICD31 is a competitive target of both mCRP and ApoE in brain endothelia in an ApoE-allele dependent pattern C_LIO_LImCRP increases CD31 phosphorylation in the brain endothelia and damages cerebrovasculature in ApoE4 carriers and AD brains C_LIO_LImCRP expression results in neuroprotective or neurodegenerative pathway activation in an ApoE-dependent manner C_LI WHAT ARE THE CLINICAL IMPLICATIONS?O_LIAlthough ApoE4 is a major genetic risk factor of AD, some ApoE4 carriers do not develop AD by the age of 90. C_LIO_LIElderly people often experience peripheral inflammatory attacks and develop chronic low-grade inflammation, which results in the formation and release of mCRP. Because CRP is routine clinical laboratory test, clinicians can use blood CRP level to predict AD risk in ApoE4 carriers. C_LIO_LIEvidence of Apoe4 genotype and chronic low-grade inflammation stages marked by elevated CRP levels should be targeted in personalized treatment and clinical trials for AD. C_LI

neuroscience↗