Roles of blood monocytes carrying TREM2 mutation in pathogenesis of Alzheimer's disease and its therapeutic potential in APP/PS1 mice.

Introduction: The triggering receptor expressed on myeloid cells 2 (TREM2) arginine-47-histidine (R47H) mutation is a significant risk for Alzheimer's disease (AD) with unclear mechanisms. Previous studies focused on microglial amyloid-β (Aβ) phagocytosis with less attention on the impact of TREM2 mutation on blood monocytes.

Methods: Bone marrow transplantation (BMT) models were used to assess the contribution of blood monocytes carrying TREM2 mutation to AD.

Interleukin-4 promotes the clearance of amyloid-β by monocyte through enhancing the recognition and intracellular processing of amyloid-β.

Background: Impaired clearance of amyloid-β protein (Aβ) in the peripheral system is a crucial event in the pathogenesis of sporadic Alzheimer's disease (AD). Dysfunctional monocytes with deficient clearance of Aβ and increased secretion of pro-inflammatory factors in the periphery are considered to contribute to AD development. Multiple studies suggest that IL-4 can inhibit the inflammatory response and enhance the expression and activity of cathepsin protease associated with intracellular clearance of Aβ by monocytes.

Adipose Tissue-Resident Sphingomonas Paucimobilis Suppresses Adaptive Thermogenesis by Reducing 15-HETE Production and Inhibiting AMPK Pathway.

Obesity represents a low-grade chronic inflammation status, which is associated with compromised adaptive thermogenesis. However, the mechanisms underlying the defective activation of thermogenesis in chronic inflammation remain unclear. Here, a chronic inflammatory model is first estabolished by injecting mice with low-dose lipopolysaccharide (LPS) before cold exposure, and then it is verified that LPS treatment can decrease the core body temperature of mice and alter the microbial distribution in epididymal white adipose tissue (eWAT).

Autoantibodies to BACE1 promote Aβ accumulation and neurodegeneration in Alzheimer's disease.

The profile of autoantibodies is dysregulated in patients with Alzheimer's disease (AD). Autoantibodies to beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) are present in human blood. This study aims to investigate the clinical relevance and pathophysiological roles of autoantibodies to BACE1 in AD.

Association of air pollutants with psychiatric disorders: a two-sample Mendelian randomization.

Background: The link between air pollution and increased risk of psychiatric disorders has been growing in evidence. However, the causal relationship between air pollution and psychiatric disorders remains poorly understood.

Methods: Single-nucleotide polymorphisms associated with air pollutants (including NOx, NO, PM, PM, and PM) from the UK Biobank were used as instrumental variables.

Tracking cognitive trajectories in older survivors of COVID-19 up to 2.5 years post-infection.

Emerging evidence suggests that neurological and other post-acute sequelae of COVID-19 can persist beyond or develop following SARS-CoV-2 infection. However, the long-term trajectories of cognitive change after a COVID-19 infection remain unclear. Here we investigated cognitive changes over a period of 2.

Crosstalk between bone and brain in Alzheimer's disease: Mechanisms, applications, and perspectives.

Alzheimer's disease (AD) is a neurodegenerative disease that involves multiple systems in the body. Numerous recent studies have revealed bidirectional crosstalk between the brain and bone, but the interaction between bone and brain in AD remains unclear. In this review, we summarize human studies of the association between bone and brain and provide an overview of their interactions and the underlying mechanisms in AD.

Rejuvenation of peripheral immune cells attenuates Alzheimer's disease-like pathologies and behavioral deficits in a mouse model.

Immunosenescence contributes to systematic aging and plays a role in the pathogenesis of Alzheimer's disease (AD). Therefore, the objective of this study was to investigate the potential of immune rejuvenation as a therapeutic strategy for AD. To achieve this, the immune systems of aged mice were rejuvenated through young bone marrow transplantation (BMT).

Blood-based CNS regionally and neuronally enriched extracellular vesicles carrying pTau217 for Alzheimer's disease diagnosis and differential diagnosis.

Accurate differential diagnosis among various dementias is crucial for effective treatment of Alzheimer's disease (AD). The study began with searching for novel blood-based neuronal extracellular vesicles (EVs) that are more enriched in the brain regions vulnerable to AD development and progression. With extensive proteomic profiling, GABRD and GPR162 were identified as novel brain regionally enriched plasma EVs markers.

Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside.

The aetiologies and origins of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), are complex and multifaceted. A growing body of evidence suggests that the gut microbiome plays crucial roles in the development and progression of neurodegenerative diseases. Clinicians have come to realize that therapeutics targeting the gut microbiome have the potential to halt the progression of neurodegenerative diseases.

Disease trajectories in older adults with non-AD pathologic change and comparison with Alzheimer's disease pathophysiology: A longitudinal study.

Based on the 'AT(N)' system, individuals with normal amyloid biomarkers but abnormal tauopathy or neurodegeneration biomarkers are classified as non-Alzheimer's disease (AD) pathologic change. This study aimed to assess the long-term clinical and cognitive trajectories of individuals with non-AD pathologic change among older adults without dementia, comparing them to those with normal AD biomarkers and AD pathophysiology. Analyzing Alzheimer's Disease Neuroimaging Initiative data, we evaluated clinical outcomes and conversion risk longitudinally using mixed effects models and multivariate Cox proportional hazard models.

CHIT1-positive microglia drive motor neuron ageing in the primate spinal cord.

Ageing is a critical factor in spinal-cord-associated disorders, yet the ageing-specific mechanisms underlying this relationship remain poorly understood. Here, to address this knowledge gap, we combined single-nucleus RNA-sequencing analysis with behavioural and neurophysiological analysis in non-human primates (NHPs). We identified motor neuron senescence and neuroinflammation with microglial hyperactivation as intertwined hallmarks of spinal cord ageing.

Association of Adipokines with Alzheimer's Disease in a Chinese Cohort.

Background: The correlation between plasma adipose factor levels and Alzheimer's patients is not entirely clear.

Objective: We aimed to investigate associations between AD and plasma levels of three adipokines including plasma adiponectin, leptin, and resistin.

Methods: A single-center, cross-sectional study recruited AD patients (n = 148) and cognitively normal (CN) controls (n = 110).

Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer's Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice.

Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation.

The Diagnostic Potential of Circulating Autoantibodies to Amyloid-β in Alzheimer's Disease.

Background: The profile of naturally occurring antibodies to amyloid-β (NAbs-Aβ) is altered in patients with Alzheimer's disease (AD). However, the diagnostic potential of NAbs-Aβ for AD is not clear yet.

Objective: This study aims to investigate the diagnostic capacities of NAbs-Aβ for AD.

Improving Blood Monocyte Energy Metabolism Enhances Its Ability to Phagocytose Amyloid-β and Prevents Alzheimer's Disease-Type Pathology and Cognitive Deficits.

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear.