Plasma proteomics identify biomarkers and undulating changes of brain aging.

Proteomics enables the characterization of brain aging biomarkers and discernment of changes during brain aging. We leveraged multimodal brain imaging data from 10,949 healthy adults to estimate brain age gap (BAG), an indicator of brain aging. Proteome-wide association analysis across 4,696 participants of 2,922 proteins identified 13 significantly associated with BAG, implicating stress, regeneration and inflammation.

Neuronal double-stranded DNA accumulation induced by DNase II deficiency drives tau phosphorylation and neurodegeneration.

Background: Deoxyribonuclease 2 (DNase II) plays a key role in clearing cytoplasmic double-stranded DNA (dsDNA). Deficiency of DNase II leads to DNA accumulation in the cytoplasm. Persistent dsDNA in neurons is an early pathological hallmark of senescence and neurodegenerative diseases including Alzheimer's disease (AD).

Novel inflammatory and insulin resistance indices provide a clue in cerebral amyloid angiopathy.

This study investigated the correlation of newly identified inflammatory and insulin resistance indices with cerebral amyloid angiopathy (CAA), and explored their potential to differentiate CAA from hypertensive arteriopathy (HA). We retrospectively analyzed 514 consecutive patients with cerebral small vessel disease (CSVD)-related haemorrhage, comparing the differences in novel inflammatory and insulin resistance indices between patients with CAA and HA. Univariate regression, LASSO and multivariate regression were used to screen variables and construct a classification diagnosis nomogram.

Identification and validation of cortisol-related hub biomarkers and the related pathogenesis of biomarkers in Ischemic Stroke.

Background: Ischemic stroke is a disease in which cerebral blood flow is blocked due to various reasons, leading to ischemia, hypoxia, softening, and even necrosis of brain tissues. The level of cortisol is related to the occurrence and progression of ischemic stroke. However, the mechanism governing their interrelationship is still unclear.

Spatiotemporal expression and coexpression patterns of SRPK1 in the human brain: A neurodevelopmental perspective.

Background: SRPK1 is a splicing-related protein that plays an important role in the development and function of the human brain. This article presents evidence that SRPK1 has distinct spatiotemporal expression patterns enriched in processes related to neurodevelopmental disorders across development.

Material And Method: We used the BrainSpan growing mammalian brain transcriptome to evaluate the distribution of SRPK1 throughout the entire brain.

Joint analysis of proteome, transcriptome, and multi-trait analysis to identify novel Parkinson's disease risk genes.

Genome-wide association studies (GWAS) have identified multiple risk variants for Parkinson's disease (PD). Nevertheless, how the risk variants confer the risk of PD remains largely unknown. We conducted a proteome-wide association study (PWAS) and summary-data-based mendelian randomization (SMR) analysis by integrating PD GWAS with proteome and protein quantitative trait loci (pQTL) data from human brain, plasma and CSF.

Clearance dysfunction of trans-barrier transport and lymphatic drainage in cerebral small vessel disease: Review and prospect.

Cerebral small vessel disease (CSVD) causes 20%-25% of stroke and contributes to 45% of dementia cases worldwide. However, since its early symptoms are inconclusive in addition to the complexity of the pathological basis, there is a rather limited effective therapies and interventions. Recently, accumulating evidence suggested that various brain-waste-clearance dysfunctions are closely related to the pathogenesis and prognosis of CSVD, and after a comprehensive and systematic review we classified them into two broad categories: trans-barrier transport and lymphatic drainage.

Integrating single-nucleus sequence profiling to reveal the transcriptional dynamics of Alzheimer's disease, Parkinson's disease, and multiple sclerosis.

Background: Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS) are three nervous system diseases that partially overlap clinically and genetically. However, bulk RNA-sequencing did not accurately detect the core pathogenic molecules in them. The availability of high-quality single cell RNA-sequencing data of post-mortem brain collections permits the generation of a large-scale gene expression in different cells in human brain, focusing on the molecular features and relationships between diseases and genes.

Identifying causal genes for migraine by integrating the proteome and transcriptome.

Background: While previous genome-wide association studies (GWAS) have identified multiple risk variants for migraine, there is a lack of evidence about how these variants contribute to the development of migraine. We employed an integrative pipeline to efficiently transform genetic associations to identify causal genes for migraine.

Methods: We conducted a proteome-wide association study (PWAS) by combining data from the migraine GWAS data with proteomic data from the human brain and plasma to identify proteins that may play a role in the risk of developing migraine.

Correlation between neutrophil gelatinase phase lipocalin and cerebral small vessel disease.

Background: Cerebral small vessel disease (CSVD) is common in the elderly population. Neutrophil gelatinase-associated lipocalin (NGAL) is closely related to cardiovascular and cerebrovascular diseases. NGAL causes pathological changes, such as damage to the vascular endothelium, by causing inflammation, which results in other related diseases.

Effects of exercise interventions in Alzheimer's disease: A meta-analysis.

Objective: The aim of this study was to investigate the clinical efficacy of exercise intervention in the treatment of patients with Alzheimer's disease (AD) by meta-analysis.

Methods: From January 2000 to January 2022, PubMed, Web of Science, Embase, CNKI, and WanFang databases were searched for all studies on the clinical efficacy of exercise intervention in the treatment of AD patients. Stata 17.

ArhGAP11A mediates amyloid-β generation and neuropathology in an Alzheimer's disease-like mouse model.

Amyloid-β (Aβ) plays an important role in the neuropathology of Alzheimer's disease (AD), but some factors promoting Aβ generation and Aβ oligomer (Aβo) neurotoxicity remain unclear. We here find that the levels of ArhGAP11A, a Ras homology GTPase-activating protein, significantly increase in patients with AD and amyloid precursor protein (APP)/presenilin-1 (PS1) mice. Reducing the ArhGAP11A level in neurons not only inhibits Aβ generation by decreasing the expression of APP, PS1, and β-secretase (BACE1) through the RhoA/ROCK/Erk signaling pathway but also reduces Aβo neurotoxicity by decreasing the expressions of apoptosis-related p53 target genes.

Physiological β-amyloid clearance by the liver and its therapeutic potential for Alzheimer's disease.

Cerebral amyloid-β (Aβ) accumulation due to impaired Aβ clearance is a pivotal event in the pathogenesis of Alzheimer's disease (AD). Considerable brain-derived Aβ is cleared via transporting to the periphery. The liver is the largest organ responsible for the clearance of metabolites in the periphery.

Single-nucleus transcriptional profiling uncovers the reprogrammed metabolism of astrocytes in Alzheimer's disease.

Astrocytes play an important role in the pathogenesis of Alzheimer's disease (AD). It is widely involved in energy metabolism in the brain by providing nutritional and metabolic support to neurons; however, the alteration in the metabolism of astrocytes in AD remains unknown. Through integrative analysis of single-nucleus sequencing datasets, we revealed metabolic changes in various cell types in the prefrontal cortex of patients with AD.

GGC repeat expansion in NOTCH2NLC induces dysfunction in ribosome biogenesis and translation.

GGC repeat expansion in the 5' untranslated region (UTR) of NOTCH2NLC is associated with a broad spectrum of neurological disorders, especially neuronal intranuclear inclusion disease (NIID). Studies have found that GGC repeat expansion in NOTCH2NLC induces the formation of polyglycine (polyG)-containing protein, which is involved in the formation of neuronal intranuclear inclusions. However, the mechanism of neurotoxicity induced by NOTCH2NLC GGC repeats is unclear.

Genetic analysis of the ATP11B gene in Chinese Han population with cerebral small vessel disease.

Background: A loss-of-function mutation in ATPase phospholipid transporting 11-B (putative) (ATP11B) gene causing cerebral small vessel disease (SVD) in vivo, and a single intronic nucleotide polymorphism in ATP11B: rs148771930 that was associated with white matter hyperintensities burden in European patients with SVD, was recently identified. Our results suggest that ATP11B may not play an essential role in SVD in the Chinese population.

Results: We performed target region sequencing including ATP11B gene in 182 patients with sporadic SVD, and identified five rare variants and two novel variants of ATP11B.

Human blood metabolites and lacunar stroke: A Mendelian randomization study.

Background: Lacunar stroke accounts for a quarter of all strokes, but little is known about the underlying pathological mechanisms. Analysis of serum metabolites may allow better understanding of the underlying biological processes. Mendelian randomization (MR) can provide information on the causality of associations.