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Background: The relationship of systolic blood pressure variability (SBPV) with Alzheimer's disease (AD) remains controversial. We aimed to explore the roles of SBPV in predicting AD incidence and to test the pathways that mediated the relationship of SBPV with cognitive functions. Methods: Longitudinal data across 96 months (T0 to T4) were derived from the Alzheimer's disease Neuroimaging Initiative cohort. SBPV for each participant was calculated based on the four measurements of SBP across 24 months (T0 to T3). At T3, logistic regression models were used to test the SBPV difference between 86 new-onset AD and 743 controls. Linear regression models were used to test the associations of SBPV with cognition and AD imaging endophenotypes for 743 non-demented participants (median age = 77.0, female = 42%). Causal mediation analyses were conducted to explore the effects of imaging endophenotypes in mediating the relationships of SBPV with cognitive function. Finally, Cox proportional hazard model was utilized to explore the association of SBPV with incident risk of AD (T3 to T4, mean follow-up = 3.5 years). Results: Participants with new-onset AD at T3 had significantly higher SBPV compared to their controls (p = 0.018). Higher SBPV was associated with lower scores of cognitive function (p = 0.005 for general cognition, p = 0.029 for memory, and p = 0.016 for executive function), higher cerebral burden of amyloid deposition by AV45 PET (p = 0.044), lower brain metabolism by FDG PET (p = 0.052), and higher burden of white matter hyperintensities (WMH) (p = 0.012). Amyloid pathology, brain metabolism, and WMH partially (ranging from 17.44% to 36.10%) mediated the associations of SBPV with cognition. Higher SBPV was significantly associated with elevated risk of developing AD (hazard ratio = 1.29, 95% confidence interval = 1.07 to 1.57, p = 0.008). Conclusion: These findings supported that maintaining stable SBP in late life helped lower the risk of AD, partially by modulating amyloid pathology, cerebral metabolism, and cerebrovascular health. [ABSTRACT FROM AUTHOR]

Β-site amyloid precursor protein (APP) cleaving enzyme (BACE1) is a crucial protease in the production of amyloid-β (Aβ) in Alzheimer's disease (AD) patients. However, the side effects observed in clinical trials of BACE1 inhibitors, including reduction in brain volume and cognitive worsening, suggest that the exact role of BACE1 in AD pathology is not fully understood. To further investigate this, we examined cerebrospinal fluid (CSF) levels of BACE1 and its cleaved product sAPPβ that reflects BACE1 activity in the China Aging and Neurodegenerative Disorder Initiative cohort. We found significant correlations between CSF BACE1 or sAPPβ levels and CSF Aβ40, Aβ42, and Aβ42/Aβ40 ratio, but not with amyloid deposition detected by 18F-Florbetapir PET. Additionally, CSF BACE1 and sAPPβ levels were positively associated with cortical thickness in multiple brain regions, and higher levels of sAPPβ were linked to increased cortical glucose metabolism in frontal and supramarginal areas. Interestingly, individuals with higher baseline levels of CSF BACE1 exhibited slower rates of brain volume reduction and cognitive worsening over time. This suggests that increased levels and activity of BACE1 may not be the determining factor for amyloid deposition, but instead, may be associated with increased neuronal activity and potentially providing protection against neurodegeneration in AD. [ABSTRACT FROM AUTHOR]

In this study, four new species of Russula subg. Brevipedum collected from China are described based on morphological characteristics and molecular evidence. Russula brevispora has a white body whose whole parts often stain brownish-orange or grayish-orange, extremely crowded lamellae with the presence of lamellulae, basidiospores with low warts and an inamyloid suprahilar spot, and clavate or lageniform hymenial cystidia often with a papillary or submoniliform appendage. Russula flavescens is characterized by a white pileus often turning yellowish brown when touched, white lamellae turning brown or light orange, basidiospores with an inamyloid suprahilar spot, and fusiform hymenial cystidia often with an appendage. Russula longicollis is morphologically characterized by a white pileus, turning grayish orange when bruised, white lamellae turning pale yellow when bruised, basidiospores with isolated warts and an amyloid suprahilar spot, and fusiform hymenial cystidia usually with a long appendage. Russula pseudojaponica has a yellowish-brown pileus center, yellowish lamellae unchanging when bruised, basidiospores with low warts and an inamyloid suprahilar spot, clavate hymenial cystidia often with a papillary appendage, and clavate pileocystidia with granulose contents. Phylogenetic analyses showed that R. flavescens, R. brevispora, and R. pseudojaponica are members of the subsect. Pallidosporinae, whereas R. longicollis belongs to subsect. Lactarioideae, and is somewhat related to R. leucocarpa. [ABSTRACT FROM AUTHOR]

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Introduction: Familial amyloid polyneuropathy is currently prevalent worldwide as the transthyretin (TTR) Val30Met mutation, and there are other types of mutations. The purpose of this study was to understand the clinical manifestations, electrophysiological characteristics, and outcomes of hormone-related therapy in patients with the TTR Val30Leu mutation in China. Methods: Clinical data were collected from 9 members of a family with the TTR Val30Leu mutation in China, and blood samples of 7 members of the family were sequenced. The electrophysiological examinations of 4 of them were collected and analysed. Results: A total of 7 people had the TTR gene c.148G>T missense mutation and the TTR protein Val30Leu mutation in this family, and the positive members all had similar symptoms, such as limb paraesthesia and gastrointestinal symptoms. In addition, electrophysiological examination showed abnormal nerve conduction velocity in all 4 patients. Conclusions: The clinical manifestations of this mutation involve mainly limb sensory or motor disorders or gastrointestinal symptoms or both, and the electrophysiological examination shows neurogenic damage. [ABSTRACT FROM AUTHOR]

cognitive decline (SCD) have a higher risk to develop Alzheimer’s Disease (AD). Resting-state-functional magnetic resonance imaging (rs-fMRI) was used to document neurological involvement in the two groups from the aspect of brain dysfunction. Accumulation of amyloid-β (Aβ) starts decades ago before the onset of clinical symptoms and may already have been associated with brain function in high-risk populations. However, this study aims to compare the patterns of fractional amplitude of low-frequency fluctuations (fALFF) maps between cognitively normal high-risk groups (SCD and T2DM) and healthy elderly and evaluate the association between regional amyloid deposition and local fALFF signals in certain cortical regions. Materials and methods: A total of 18 T2DM, 11 SCD, and 18 healthy elderlies were included in this study. The dierences in the fALFF maps were compared between HC and high-risk groups. Regional amyloid deposition and local fALFF signals were obtained and further correlated in two high-risk groups. Results: Compared to HC, the altered fALFF signals of regions were shown in SCD such as the left posterior cerebellum, left putamen, and cingulate gyrus. The T2DM group illustrated altered neural activity in the superior temporal gyrus, supplementary motor area, and precentral gyrus. The correlation between fALFF signals and amyloid deposition was negative in the left anterior cingulate cortex for both groups. In the T2DM group, a positive correlation was shown in the right occipital lobe and left mesial temporal lobe. Conclusion: The altered fALFF signals were demonstrated in high-risk groups compared to HC. Very early amyloid deposition in SCD and T2DM groups was observed to aect the neural activity mainly involved in the default mode network (DMN). [ABSTRACT FROM AUTHOR]

Three new species are described and illustrated here based on morphological evidence and phylogenetic analysis from China. Russulaleucomarginata is recognized by a yellowish red to reddish brown pileus center, a yellowish white to reddish white and sometimes cracked margin, and a reddish white to pastel pink stipe. Russula roseola is characterized by its reddish white to ruby red pileus center, pink to rose margin, adnate to slightly decurrent lamellae with unequal-length lamellulae, reddish white to pink stipe, and occasionally three-celled pileocystidia. Russula subsanguinaria is morphologically characterized by a reddish brown to dark brown pileus center, a reddish orange to brownish red margin with striation, a reddish white to pink stipe with an expanded base, basidiospores with moderately distant to dense amyloid warts, and hymenial cystidia turning to reddish black in SV. In this study, we performed phylogenetic analysis based on ITS sequence and 28S-RPB1-RPB2-mtSSU datasets. Detailed morphological features and phylogenetic analysis indicate that these three new species belong to Russula subg. Russula. [ABSTRACT FROM AUTHOR]

Due to its complex pathogenesis and lack of effective therapeutic methods, Alzheimer's disease (AD) has become a severe public health problem worldwide. Recent studies have discovered the function of central nervous system lymphatic drainage, which provides a new strategy for the treatment of AD. Chinese herbal medicine (CHM) has been considered as a cure for AD for hundreds of years in China, and its effect on scavenging β-amyloid protein in the brain of AD patients has been confirmed. In this review, the mechanism of central nervous system lymphatic drainage and the regulatory functions of CHM on correlation factors were briefly summarized. The advances in our understanding regarding the treatment of AD via regulating the central lymphatic system with CHM will promote the clinical application of CHM in AD patients and the discovery of new therapeutic drugs. [ABSTRACT FROM AUTHOR]

Background: Chinese Herbal Medicines (CHMs), as an important and integral part of a larger system of medicine practiced in China, called Traditional Chinese Medicine (TCM), have been used in stroke therapy for centuries. A large body of studies suggest that some Chinese herbs can help reverse cognitive impairment in stroke patients, while whether these herbs also exert therapeutic benefits for Alzheimer's disease remains to be seen.Objective: To address this issue, we selected four types of CHMs that are commonly prescribed for stroke treatment in clinical practice, namely DengZhanXiXin (D1), TongLuoJiuNao (T2), QingKaiLing (Q3), and HuangQinGan (H4), and tested their effects on amyloid-β protein precursor (AβPP) processing in vitro.Methods: AβPP, β-secretase (BACE1), and 99-amino acid C-terminal fragment of AβPP (C99) stably transfected cells were used for the tests of AβPP processing. The production of Aβ, activity of BACE1, neprilysin (NEP), and γ-secretase were assessed by ELISA, RT-PCR, and western blot.Results: By upregulating BACE1 activity, D1 increased Aβ production whereas decreased the ratio of Aβ42/Aβ40; by downregulating BACE1 activity and modulating the expression of γ-secretase, T2 decreased Aβ production and the ratio of Aβ42/Aβ40; by downregulating BACE1 activity, Q3 decreased Aβ production; H4 did not change Aβ production due to the simultaneously downregulation of BACE1 and NEP activity.Conclusion: Our study indicates that these four anti-stroke CHMs regulate AβPP processing through different mechanisms. Particularly, T2 with relatively simple components and prominent effect on AβPP processing may be a promising candidate for the treatment of AD. [ABSTRACT FROM AUTHOR]

Background: The clinical manifestations of amyloid cardiomyopathy (AC) are not specific; therefore, AC is often misdiagnosed as hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD). A differential diagnosis of these three conditions is often necessary in the clinical setting. Objectives: To investigate the differential diagnostic performance of radiomic analysis, based on cardiac magnetic resonance (CMR) native T1 mapping images for the left ventricular hypertrophy (LVH) etiologies. Methods: This retrospective, case-control study was conducted on 91 participants (68 males and 23 females; mean age: 48 ± 13 years), including 22 patients with HHD, 27 patients with AC, 28 patients with HCM, and 14 controls in Tongji Hospital (Wuhan, China). All participants underwent 3.0T CMR imaging. Besides, radiomic analyses were performed using T1 mapping images. The cases were divided into training and test datasets using a random seed. Next, the models were constructed with the training dataset and evaluated with the test dataset. Results: A total of 1,033 radiomic features were extracted in this study. Overall, 11, 28, 19, and eight features were selected to construct the basal T1 mapping, mid-chamber T1 mapping, apical T1 mapping, and multi-module conjoint models, respectively. Optimal performance was reported in the mid-chamber and basal T1 mapping models. The area under the curve (AUC), precision, recall, and F1 score were 0.96, 0.84, 0.82, and 0.83 for the mid-chamber T1 mapping model and 0.96, 0.90, 0.89, and 0.88 for the basal T1 mapping model in the independent test dataset, respectively. The lowest diagnostic performance was observed in the apical T1 mapping model. The AUC, precision, recall, and F1 score of the apical T1 mapping model were 0.86, 0.71, 0.70, and 0.70 in the independent test dataset, respectively. Conclusions: The radiomic analysis of T1 mapping could accurately distinguish the three causes of myocardial hypertrophy, including HCM, HHD, and AC. It may be also a suitable alternative to late gadolinium enhancement-CMR. [ABSTRACT FROM AUTHOR]

Background: The relationship between alcohol consumption and Alzheimer's disease (AD) pathology is unclear. Amyloid-β (Aβ) and tau biomarkers in cerebrospinal fluid (CSF) have been proven valuable in establishing prognosis in pre-clinical AD.Objective: We sought to examine the associations between alcohol consumption and CSF AD biomarkers in cognitive intact subjects.Methods: A total of 806 cognitively intact participants who had measurements of CSF Aβ, pTau, and total Tau proteins and drinking characteristics were included from the Chinese Alzheimer's Biomarker and Lifestyle (CABLE) study. Linear and logistic regression analyses were utilized to explore the associations of alcohol consumption with CSF AD biomarkers. We examined the interaction effects of age, gender, and apolipoprotein epsilon (APOE) ɛ4 status on the relationships between the frequency of drinking and CSF biomarkers.Results: The multiple linear regression analyses revealed significant differences in CSF AD biomarkers between infrequent drinking (< 1 times/week) and frequent drinking groups (≥1 times/week). Participants in frequent drinking group had higher CSF p-tau/Aβ42 and tTau/Aβ42. Frequent drinking was significantly associated with greater pTau and tTau abnormalities compared to the infrequent drinking group in older (> 65 years) participants.Conclusion: The present study showed significant associations between drinking frequency and CSF AD biomarkers in cognitively intact older adults. Alcohol consumption may have an influence on AD by modulating amyloid deposition and tau phosphorylation in the preclinical stage. [ABSTRACT FROM AUTHOR]

Background: Neuroimaging has played a primary role in predicting intracerebral hemorrhage (ICH) recurrence of cerebral amyloid angiopathy (CAA); however, the utilities of biomarkers in CAA-related ICH and cognitive impairment remain unexplored.Objective: To investigate the correlations of serum levels of matrix metalloproteinase-2 (MMP-2), MMP-3, and MMP-9 with CAA-related MRI markers, ICH recurrence, and cognitive status.Methods: 68 cases with first probable CAA-ICH and 69 controls were recruited. Clinical and imaging data were obtained at baseline and serum MMPs in the acute phase were measured by Luminex multiplex assays. Cognitive status was assessed with the Chinese version of Mini-Mental State Examination within 10-14 days after ICH onset.Results: Serum MMP-2 level was significantly lower in CAA-ICH patients than controls while MMP-9 was significantly higher. In CAA-ICH patients, MMP-3 level was significantly associated with lobar cerebral microbleeds count after adjusting age, sex, and hypertension (adjusted coefficient 0.368, 95%CI 0.099-0.637, p = 0.008). During a median follow-up of 2.4 years, higher level of MMP-2 predicted lower CAA-ICH recurrence after adjusting age (adjusted HR 0.326, 95%CI 0.122-0.871, p = 0.025), ICH volume (adjusted HR 0.259, 95%CI 0.094-0.715, p = 0.009), total MRI burden of SVD score (adjusted HR 0.350, 95%CI 0.131-0.936, p = 0.037) respectively. Besides, higher level of MMP-2 was significantly associated with decreased risk of cognitive impairment independent of age and ICH volume (adjusted OR 0.054, 95%CI 0.005-0.570, p = 0.015).Conclusion: Serum MMP-2 in acute phase might be a promising biomarker to predict CAA-ICH recurrence and to evaluate the risk of cognitive impairment. [ABSTRACT FROM AUTHOR]

Amanita chuformis, a new species in the A. pseudogemmata-A. ballerina subclade of Amanita section Phalloideae, is described from China with both multi-gene phylogenetic and morphological data. This species occurs in subalpine coniferous forests in southwestern China and is characterized by its brownish pileus decorated with conical to patch-like volval remnants, a slightly striate pileal margin, a marginate basal bulb, and weakly amyloid to amyloid, subglobose to broadly ellipsoid basidiospores measuring 9.5-11 × 8-9.5 μm. Phylogenetic analyses based on internal transcribed spacer (ITS) region, the nuclear ribosomal RNA large subunit (nrLSU) and the genes for the polymerase II second largest subunit (RPB2) and for translation elongation factor 1-α (TEF1α) indicate A. chuformis is close to A. pseudogemmata and A. levistriata. The new species is described, illustrated and compared with closely related and similar species. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study is to investigate the incremental value of amyloid positron emission tomography (Aβ-PET) in a tertiary memory clinic setting in China., Methods: A total of 1073 patients were offered Aβ-PET using 18 F-florbetapir. The neurologists determined a suspected etiology (Alzheimer's disease [AD] or non-AD) with a percentage estimate of their confidence and medication prescription both before and after receiving the Aβ-PET results., Results: After disclosure of the Aβ-PET results, etiological diagnoses changed in 19.3% of patients, and diagnostic confidence increased from 69.3% to 85.6%. Amyloid PET results led to a change of treatment plan in 36.5% of patients. Compared to the late-onset group, the early-onset group had a more frequent change in diagnoses and a higher increase in diagnostic confidence., Discussion: Aβ-PET has significant impacts on the changes of diagnoses and management in Chinese population. Early-onset cases are more likely to benefit from Aβ-PET than late-onset cases., Highlights: Amyloid PET contributes to diagnostic changes and its confidence in Chinese patients. Amyloid PET leads to a change of treatment plans in Chinese patients. Early-onset cases are more likely to benefit from amyloid PET than late-onset cases., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objective: To investigate the prognostic value of serum amyloid A (SAA) in the patients with Corona Virus Disease 2019 (COVID-19). Methods: The medical data of 89 COVID-19 patients admitted to Renmin Hospital of Wuhan University from January 3, 2020 to February 26, 2020 were collected. Eighty-nine cases were divided into survival group (53 cases) and non-survival group (36 cases) according to the results of 28-day follow-up. The SAA levels of all patients were recorded and compared on 1 day after admission (before treatment) and 3 days, 5 days, and 7 days after treatment. The ROC curve was drawn to analyze the prognosis of patients with COVID-19 by SAA. Results: The difference of comparison of SAA between survival group and non-survival group before treatment was not statistically significant, Z1 = − 1.426, P = 0.154. The Z1 values (Z1 is the Z value of the rank sum test) of the two groups of patients at 3 days, 5 days, and 7 days after treatment were − 5.569, − 6.967, and − 7.542, respectively. The P values were all less than 0.001, and the difference was statistically significant. The ROC curve results showed that SAA has higher sensitivity to the prognostic value of 1 day (before treatment), 3 days, 5 days, and 7 days after treatment, with values of 0.806, 0.972, 0.861, and 0.961, respectively. Compared with SAA on the 7th day and C-reactive protein, leukocyte count, neutrophil count, lymphocyte count, and hemoglobin on the 7th day, the sensitivities were: 96.1%, 83.3%, 88.3%, 83.3%, 67.9%, and 83.0%, respectively, of which SAA has the highest sensitivity. Conclusion: SAA can be used as a predictor of the prognosis in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background and Aim: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Southern China, Southeast Asia. Radiotherapy is the main treatment for NPC. Still, about 20% of patients with NPC have a recurrence. No effective serum biomarkers are available for recurrent nasopharyngeal carcinoma (rNPC) to date. This study aimed to explore whether amyloid beta (A4) precursor protein (APP) might serve as a valuable diagnostic and prognostic biomarker for patients with rNPC. Methods: In a previous study, a tandem mass tag–based proteomic test was performed, which screened 59 differentially expressed proteins (DEPs) between nonrecurrent nasopharyngeal carcinoma (nrNPC) and rNPC. In this study, a protein–protein interaction was conducted to screen the key proteins among the 59 DEPs. APP was validated and evaluated by enzyme-linked immunosorbent assay in 70 serum samples [recurrence (n = 35) and no-recurrence (n = 35)]. Also, the receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of APP. Results: The area under the ROC curve was 0.666 (95% CI: 0.514–0.818, P = 0.044). The best cutoff point of the relative expression levels for APP was 1.23 (concentration = 16.95 ng/mL), at which the sensitivity was 55.2% and the specificity was 90.9%. Conclusion: The findings indicated that APP might be a valuable diagnostic and prognostic biomarker for patients with rNPC. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment and the deposition of amyloid plaques in the brain. In a transgenic mouse model of AD, cognitive impairment and synaptic dysfunction were revealed to be associated with soluble amyloid oligomers and to occur prior to plaque formation. The results of our previous studies revealed that striatal-enriched protein tyrosine phosphatase (STEP)61 negatively regulated the β-amyloid protein-mediated ERK/cAMP-response element-binding protein (CREB) signaling pathway. Dl-3-n-butylphthalide (NBP) is a synthetic compound approved by the Food and Drug Administration of China for the treatment of ischemic stroke in 2002. Studies have shown that the neuroprotective effects of NBP involve multiple mechanisms. The present study further explored the mechanism of NBP therapy in amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice, and the involvement of the STEP/ERK/CREB signaling pathway. The results suggested that NBP treatment effectively ameliorated the spatial learning and memory impairment of the APP/PS1 transgenic mice, which was assessed using a Morris water maze. In addition, NBP reduced amyloid-induced activation of STEP61 levels, while increasing phosphorylated (p)-ERK1/2 and p-CREB levels in the cerebral cortex and hippocampus of APP/PS1 transgenic mice by western blotting and immunostaining. In conclusion, the present study provided evidence to suggest that the new drug NBP improved amyloid-induced learning and memory deficits, likely through the regulation of the STEP/ERK/CREB pathway. The results revealed that NBP, as a multi-target drug, may exert a neuroprotective effect. Therefore, NBP may serve as an effective treatment for AD. [ABSTRACT FROM AUTHOR]

Familial amyloid polyneuropathy (FAP) caused by a genetic mutation in transthyretin (TTR) is an autosomal dominant hereditary disease. The retrospective, observational case series study presents the ocular clinicopathological findings of five cases carrying the TTR mutation c.401A>G (p.Tyr134Cys). Multimodal retinal imaging and electrophysiological examination, Congo red staining and immunohistochemical analysis of specimens, and genetic analyses were performed. Cases 1 and 2 were symptomatic with vitreous and retinal amyloid deposition and poor visual recovery. Case 3 had a symptomatic vitreous haze in the left eye with good postoperative visual recovery. The right eye of case 3 and the eyes of cases 4 and 5 were asymptomatic. Thicker retinal nerve fiber layer, retinal venous tortuosity with prolonged arteriovenous passage time on fluorescein angiography and retinal dysfunction detected by multifocal electroretinogram occurred even in asymptomatic eyes. Moreover, the internal limiting membrane from patients with FAP was stained positive for Congo red and transforming growth factor-β1. The results highlight the amyloid deposition of mutant TTR in the optic disc and retina, even in the asymptomatic stage. The deposited amyloid leads to increased resistance to venous return and retinal functional abnormalities. Therefore, careful follow-up of structural and functional changes in the retina is needed, even in asymptomatic patients with FAP.

To investigate the relationship between amnestic mild cognitive impairment (aMCI) and candidate gene polymorphisms in a Chinese population, 116 aMCI patients and 93 normal controls were recruited. Multi-dimensional neuropsychological tests were used to extensively assess the cognitive functions of the subjects. MassARRAY and iPLEX systems were used to measure candidate single nucleotide polymorohisms (SNPs) and analyse allelic, genotypic or haplotypic distributions. The scores of the neuropsychological tests were significantly lower for the aMCI patients than for the normal controls. The distributions of SNPs relating to the amyloid cascade hypothesis (TOMM40 rs157581 G and TOMM40 rs2075650 G), to the cholesterol metabolism hypothesis (ApoE rs429358 C, LDLR rs11668477 G and CH25H rs7091822 T and PLAU rs2227564 CT) and to the tau hypothesis (MAPT/STH rs242562 GG) in aMCI were significantly different than those in normal controls. Interactions were also found in aMCI amongst SNPs in LDLR rs11668477, PLAU rs2227564, and TOMM40 rs157581, between SNPs in TOMM40 rs157580 and BACE2 rs9975138. The study suggests that aMCI is characterised by memory impairment and associated with SNPs in three systems relating to the pathogenesis of AD-those of the amyloid cascade, tau and cholesterol metabolism pathways. Interactions were also observed between genes in the amyloid pathway and between the amyloid and cholesterol pathways. [ABSTRACT FROM AUTHOR]

• Microglial activation conditionally induced the differentiation of specifically phenotypic phagocytes. • IL-10KO promoted the transformation of microglial phenotype DAM-II and its phagocytosis. • IL-10R/STAT3 negatively regulated the microglial phagocytosis. Both the total amount and annual growth rate of Alzheimer's disease (AD) patients in China are much higher than in other regions in the world. This trend of rapid growth will be difficult to change in the next few decades, hence the prevention and treatment situation of AD patients in China is more severe. Maintaining the balance between the production and removal pathways of Aβ is an important guarantee for the body to maintain its normal physiological state. The dysfunction of Aβ clearance is an important factor of Aβ accumulation in brain tissue of AD patients causing neurotoxicity of synaptic damage and neuronal death. Based on the literature review, it introduced the important role of microglias in clearing Aβ deposits in the process of Alzheimer's disease. And most of these phagocytic cells were the specific phenotype of disease-related microglia (DAM-I/DAM-II) that induced microglial differentiation after activation. IL-10KO promoted the transformation of microglial phenotype DAM-II, and enhanced its phagocytosis for Aβ oligomers. There is a hypothesis that IL-10R/STAT3 negatively regulates microglial phagocytosis. It was learnt that blocking the IL-10R/STAT3 pathway promoted microglial activation and enhanced phagocytosis. The comprehensive review on the involvement of IL-10R/STAT3 pathway in the process of AD would open up new ideas and discover new targets for the development of new therapeutic drugs. [ABSTRACT FROM AUTHOR]

Familial amyloidotic polyneuropathy type 1 (FAP1, MIM176300) is an autosomal dominant disease caused by mutations in the transthyretin (TTR ) gene. An extended Chinese kindred of FAP1 was first reported in Hong Kong in 1989, three of the four histologically proven subjects have deceased. TTR gene mutations were not studied then. A DNA-based diagnosis was performed on FAP1 by restriction analysis and direct DNA sequencing was carried out on a symptomatic member of this family who had undergone a liver transplantation. It showed a substitution of thymine by cytosine in the second base of codon 30 in exon 2 of the TTR gene, with the creation of a novel Hha I restriction endonuclease site. Valine is substituted by alanine (V30A) in the mutant TTR . Both restriction analysis and direct sequencing revealed the same mutation in one of the two asymptomatic siblings. This mutation was first reported in a FAP1 family of German descent. [ABSTRACT FROM AUTHOR]

Background Apolipoprotein E (apoE) is present in a variety of biochemically different amyloid deposits, including Alzheimer's disease, systemic amyloidosis and primary cutaneous amyloidosis (PCA). Among the three closely related alleleic forms of apoE, the ε4 allele is linked to Alzheimer's disease. Apolipoprotein A-I (apoA-I), another apolipoprotein, is also found in senile plaques of Alzheimer's disease and in amyloid of aortic atherosclerotic plaques. Furthermore, apoA-I has recently been found to be associated with hereditary cutaneous and cardiac amyloidosis. Objectives To determine whether the apoE ε4 allele is associated with increased risk of PCA and whether apoE and apoA-I are present in PCA and common secondary cutaneous amyloidosis (SCA) (i.e. basal cell carcinoma, Bowen's disease and seborrhoeic keratosis). Methods We examined the apoE genotype in 57 Chinese patients with PCA and 58 normal healthy control subjects of similar age. In addition, immunohistochemical staining was performed to determine the localization of apoE and apoA-I in skin tissues from 15 patients with SCA and 15 with PCA. Results The frequency of the ε4 allele in the PCA group was not significantly higher than that in the control group (8·8% vs. 6·9%, P > 0·05). ApoE was present in amyloid deposits in both PCA and SCA, but apoA-I was not detected in these cutaneous amyloid deposits. Conclusions ApoE is also a component of amyloid deposits in SCA. Although the genetic susceptibility of certain apoE isoforms may not be a crucial factor in the development of PCA and, although apoA-I is not associated with amyloid deposits of PCA and SCA, the role of apolipoproteins in amyloidogenesis deserves further scrutiny. [ABSTRACT FROM AUTHOR]

Introduction. Familial amyloid polyneuropathy (FAP) is a rare autosomal dominant peripheral neuropathy. We report a case series of Malaysian FAP patients. Methods. Patients with definite (genetically confirmed) FAP seen at the University of Malaya Medical Centre between 2008 till 2019 were included in the series. The patients' demographic and clinical features and investigations including nerve conduction studies and electromyography (NCS/EMG), echocardiography, sural nerve biopsy and hATTR mutation are reported. Results. A total 21 index cases were seen. Nineteen (90%) were ethnic Chinese, one ethnic (5%) Malay and one (5%) ethnic Indian; Fourteen (67%) were men. Mean age of onset of symptoms was 56.1 ± 10.5 years (range: 31-73). Nineteen (90%) patients presented with numbness and weakness of the limbs while two had postural hypotension. Fifteen (71%) patients had positive family history. NCS/EMG showed sensorimotor polyneuropathy in 19 (90%) patients; fifteen (71%) showing axonal neuropathy. Amyloid deposits were seen on nerve biopsy in ten patients and rectal, leptomeningeal and endomyocardial biopsies in 1 patient respectively. The latter was diagnosed as familial amyloid cardiomyopathy (FAC). Sixteen patients (76%) had abnormal cardiac echocardiogram with amyloid deposits. Fifteen Chinese patients (71%) carried the Ala97Ser hATTR mutation while the FAC patient has Asp39Val mutation. Our Malay patient had Glu54Lys mutation and Indian patient had Gly67Val mutation. Two patients carried Val30Met mutation. Autonomic function test was abnormal in all 7 patients in whom they were carried out. Conclusion. FAP in Malaysians is seen mainly among ethnic Chinese, in whom Ala97Ser may be a common mutation. This is also the reported "hotspot" mutation for FAP reported in Taiwan but not in China. Similar to Taiwan, Chinese-Malaysians are descended from immigrants from Southern China. Similar to Taiwanese patients, our FAP patients with Ala97Ser mutation, present with late-onset progressive sensorimotor polyneuropathy and cardiac involvement was common. [ABSTRACT FROM AUTHOR]

As brain insults, sleep disorders could enhance microglial activation and aggravate neuroinflammation. Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) serves as a readout for TREM2-associated microglial responses. We aimed to study the association of sleep characteristics with CSF sTREM2 in cognitively normal (CN) older adults. Linear and non-linear regression analyses were conducted in 830 participants with measurements of sleep characteristics and CSF sTREM2, after adjusting for age, sex, education, the Chinese-Modified Mini-Mental State Examination (CM-MMSE) scores, and APOE4 status. These analyses were also performed in amyloid-negative (A -) and amyloid-positive (A +) individuals. Linear relationships between sleep characteristics and CSF sTREM2 were found. In all the participants, sleep efficiency score in Pittsburgh Sleep Quality Index (PSQI) (p = 0.037) showed a positive linear association with CSF sTREM2. In A + individuals, the grade of PSQI total score (p = 0.011) as well as subjective sleep quality score (p = 0.048) and sleep efficiency score (p < 0.001) in PSQI were positively associated with CSF sTREM2. Besides, several U-shaped relationships were revealed of sleep-time measures, such as insufficient or excessive nocturnal sleep duration, with CSF sTREM2 in A + individuals (the optimal model: bedtime 22:21 p.m., time to fall asleep 22:52 p.m., nocturnal sleep duration 7.36 h). In A - individuals, the above relationships were not found. Poor self-reported sleep characteristics and sleep indicators were associated with higher CSF sTREM2, suggesting that sleep might play an important role in the regulation of TREM2-associated microglial activity., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Four new cembranoids (1 – 4) were isolated from the extracts of a soft coral collected from the sea area near Xisha Island, South China Sea. The structures of these compounds were determined mainly by spectroscopic analyses, with the absolute configuration of 1 being established by X - ray diffraction analysis. In bioassay, compounds 1 and 3 displayed moderate inhibitory activity against Aβ 42 aggregation (20.6% and 37.2% inhibition at 10 μM). The binding mode of 1 with Aβ 42 monomer was predicted by molecular docking. In addition, compounds 1 and 3 did not show cytotoxicity against human tumor cell lines (SH-SY5Y, MDA-MB-426, A549, Hep3B, and HT-29) at 100 μM. Taken together, these cembranoids as new anti-Aβ aggregation agents derived from Sinularia sp. provided a new chemical scaffold for anti-Alzhemer's disease drug discovery. Unlabelled Image [ABSTRACT FROM AUTHOR]

Anionic antimicrobial peptides (AAMPs) with net charges ranging from -1 to -8 have been identified in frogs, toads, newts and salamanders across Africa, South America and China. Most of these peptides show antibacterial activity and a number of them are multifunctional, variously showing antifungal activity, anticancer action, neuropeptide function and the ability to potentiate conventional antibiotics. Antimicrobial mechanisms proposed for these AAMPs, include toroidal pore formation and the Shai-Huang-Matsazuki model of membrane interaction along with pH dependent amyloidogenesis and membranolysis via tilted peptide formation. The potential for therapeutic and biotechnical application of these AAMPs has been demonstrated, including the development of amyloid-based nanomaterials and antiviral agents. It is concluded that amphibian AAMPs represent an untapped potential source of biologically active agents and merit far greater research interest., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Abstract: Toll-like receptor 2 (TLR2) represents a reasonable functional and positional candidate gene for Alzheimer''s disease (AD) as it is located under the linkage region of AD on chromosome 4q, and is functionally involved in the microglia-mediated inflammatory response and amyloid β (Aβ) clearance. In the current study, 7 single nucleotide polymorphisms (SNPs) that span the TLR2 were selected and their associations with late-onset AD (LOAD) risk were assessed in a case-control sample comprising 785 individuals in a Han Chinese population. No significant differences in the frequency of TLR2 alleles, genotypes, and haplotypes in the AD cases were detected compared with the controls. TLR2 gene might not play a major role in the genetic predisposition to late-onset Alzheimer''s disease in this population. [Copyright &y& Elsevier]