Exploring the vital role of microglial membrane receptors in Alzheimer’s disease pathogenesis: a comprehensive review

Neurodegenerative diseases constitute a broad category of diseases caused by the degeneration of the neurons.They are mainly manifested by the gradual loss of neuron structure and function and eventually can cause death or loss of neurons.As the global population ages rapidly,increased people are being diagnosed with neurodegenerative diseases.It has been established that the onset of Alzheimer’s disease(AD)is closely linked with increasing age and its major pathological features include amyloid-beta plaques(Aβ),Tau hyperphosphorylation,Neurofibrillary tangles(NFTs),neuronal death as well as synaptic loss.The involvement of microglia is crucial in the pathogenesis and progression of AD and exhibits a dual role.For instance,in the early stage of AD,microglia surface membrane proteins or receptors can participate in immunophagocytosis,and anti-inflammatory functions and act as a physical barrier after recognizing various ligands such as Aβand NFTs.However,in the later stage of the disease,membrane receptors on the surface of microglia can cause its activation to release a substantial quantity of pro-inflammatory factors.Which can amplify the neuroinflammatory response.The rapid decline of normal immune phagocytosis can result in the continuous accumulation of abnormal proteins,leading to neuronal dysfunction and destruction of the formed physical barrier as well as the neurovascular microenvironment.It can also increase the transformation of microglia from anti-inflammatory phenotype M2 to pro-inflammatory phenotype M1,induce severe neuronal injury or apoptosis,and aggravate the progression of AD.Due to few articles have focused on the AD-related membrane protein receptors on microglia,thus in this paper,we have reviewed several representative microglial membrane proteins or receptors about their specific roles and functions implicated in AD,and expect that there will be more in-depth research and scientific research results in the treatment of AD by targeted regulation of microglia membrane protein receptors in the future.

Development and validation of a novel nomogram to predict aneurysm rupture in patients with multiple intracranial aneurysms:a multicentre retrospective study

Background and purpose Approximately 15%–45%of patients with unruptured intracranial aneurysms have multiple intracranial aneurysms(MIAs).Determining which one is most likely to rupture is extremely important for treatment decision making for MIAs patients.This study aimed to develop and validate a nomogram to evaluate the per-aneurysm rupture risk of MIAs patients.Methods A total of 1671 IAs from 700 patients with MIAs were randomly dichotomised into derivation and validation sets.Multivariate logistic regression analysis was used to select predictors and construct a nomogram model for aneurysm rupture risk assessment in the derivation set.The discriminative accuracy,calibration performance and clinical usefulness of this nomogram were assessed.We also developed a multivariate model for a subgroup of 158 subarachnoid haemorrhage(SAH)patients and compared its performance with the nomogram model.Results Multivariate analyses identified seven variables that were significantly associated with IA rupture(history of SAH,alcohol consumption,female sex,aspect ratio>1.5,posterior circulation,irregular shape and bifurcation location).The clinical and morphological-based MIAs(CMB-MIAs)nomogram model showed good calibration and discrimination(derivation set:area under the curve(AUC)=0.740 validation set:AUC=0.772).Decision curve analysis demonstrated that the nomogram was clinically useful.Compared with the nomogram model,the AUC of multivariate model developed from SAH patients had lower value of 0.730.Conclusions This CMB-MIAs nomogram for MIAs rupture risk is the first to be developed and validated in a large multi-institutional cohort.This nomogram could be used in decision-making and risk stratification in MIAs patients.

Acute Ischaemic Stroke Cooperation Group of Endovascular Treatment (ANGEL) registry: study protocol for a prospective, multicentre registry in China

Background and purpose Endovascular treatment could improve functional outcomes and reduce mortality in patients with intracranial large artery occlusion. This registry aims to evaluate the endovascular treatment delivery and to improve endovascular treatment algorithm in clinical practice for patients with stroke in China. Methods and analysis This multicentric, nationwide, prospective registry plans to include 20 stroke centres and recruit 900 consecutive AIS patients with large- artery occlusion under endovascular treatment. This registry will enrol acute large vessel occlusion patients suitable for endovascular treatment and the inclusion and exclusion criteria. In this study, 90 days functional independence (modified Rankin Scale score ≤2) is the primary efficacy endpoint. The procedural efficacy endpoint of this registry is target artery recanalisation defined by modified Thrombolysis in Cerebral Infarction score 2b or 3 after endovascular therapy. Symptomatic intracranial haemorrhage with 24±3 hours after the procedure is the primary safety endpoint of this registry. Ethics and dissemination Beijing Tiantan Hospital’s Ethics committee and all other participating centres approved the protocol and data collection of Acute Ischaemic Stroke Cooperation Group of Endovascular Treatment registry. Each participant or representative had a written informed consent.

Safety and efficacy of oral antiplatelet for patients who had acute ischaemic stroke undergoing endovascular therapy

Background and purpose To investigate the safety and efficacy of oral antiplatelet therapy(APT)for patients who had acute ischaemic stroke(AIS),receiving endovascular therapy(EVT).Methods Patients were divided into non-APT group and APT(single APT or dual APT(DAPT)group.The safety and efficacy endpoints at 3-month follow-up were symptomatic intracranial haemorrhage(sICH),recanalisation rate,clinical outcome and mortality.Results Among 915 patients who had AIS,those in APT group(n=199)showed shorter puncture-to recanalisation time,lower frequency of intravenous thrombolysis and more use of tirofiban compared with those in non-antiplatelet group(n=716)(p<0.05 for all).Oral APT was found to be associated with superior clinical outcome compared with non-APT(APT(44.2%)versus non-APT(41.1%)),adjusted OR=2.605,95% CI 1.244 to 5.455,p=0.011).DAPT showed superior clinical outcome compared with non-APT(DAPT(56.5%)versus non-APT(41.1%),adjusted OR=5.405,95% CI 1.614 to 18.102,p=0.006)and lower risk of mortality at 3-month follow-up(DAPT(4.8%)versus non-DAPT(17.7%),adjusted OR=0.008,95%CI 0.000 to 0.441,p=0.019).There was no significant difference in sICH between the two groups.Conclusions Oral APT prior to undergoing EVT is safe and may accompany with superior clinical outcomes.DAPT may associate with superior clinical outcomes and lower risk of mortality.