Alzheimer's disease (AD) is the most common neurodegenerative disease mainly caused by abnormal tau phosphorylation, amyloid β (Aβ) deposition and neuroinflammation. As an important environmental factor, hypoxia has been reported to aggravate AD via exacerbating Aβ and tau pathologies. However, the link between hypoxia and neuroinflammation, especially the changes of pro-inflammatory M1 or anti-inflammation M2 microglia phenotypes in AD, is still far from being clearly investigated. Here, we evaluated the activation of microglia in the brains of APPswe/PS1dE9 transgenic (Tg) mice and their wild type (Wt) littermates, after a single episode of acute hypoxia (24 hours) exposure. We found that acute hypoxia facilitated the activation of M1 microglia in both Tg and Wt mice as evidenced by the elevated M1 markers including cluster of differentiation 86 (CD86), tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2) and CCL3. In addition, the markers of M2 microglia phenotype (Arg-1, CD206, IL-4 and IL-10) were decreased after acute hypoxia exposure, suggesting an attenuated M2 phenotype of microglia. Moreover, the activation of microglial and the release of cytokines and chemokines were associated with Nuclear factor-κB (NF-κB) induction through toll-like receptor 4 (TLR4). In summary, our findings revealed that acute hypoxia facilitated the activation of M1 microglia and attenuated the activation of M2 microglia in a transgenic AD mouse model, indicating the pathological role of hypoxia in the neuroinflammation of AD.

Rapid eye movement sleep behavior disorder (RBD) is a sleep behavior disorder characterized by abnormal behaviors and loss of muscle atonia during rapid eye movement (REM) sleep. RBD is generally considered to be associated with synucleinopathies, such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), and usually precedes years before the first symptom of these diseases. It is believed that RBD predicts the neurodegeneration in synucleinopathy. However, increasing evidences have shown that RBD is also found in non-synucleinopathy neurodegenerative diseases, including Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), etc. Sleep disturbance such as RBD may be an early sign of neurodegeneration in these diseases, and also serve as an assessment of cognitive impairments. In this review, we updated the clinical characteristics, diagnosis, and possible mechanisms of RBD in neurogenerative diseases. A better understanding of RBD in these neurogenerative diseases will provide biomarkers and novel therapeutics for the early diagnosis and treatment of the diseases.

The C-type lectins DC-SIGN, DC-SIGNR and LSECtin are encoded by the lectin gene cluster on chromosome 19p13.3 and perform cell-adhesion and pathogen recognition functions on dendritic cells, liver cells and lymph node sinusoidal endothelial cells. DC-SIGN and DC-SIGNR share similar overall gene and protein molecule structures, and they exhibit high affinity for high-mannose carbohydrates. LSECtin, a Ca2+-dependent C-type lectin, interacts with mannose, NAcGlc and fucose. These lectins allow pathogen recognition (e.g., viruses, bacteria and allergens) and cell adhesion for dendritic and endothelial cells in different tissues, which may enhance the infection and facilitate the spread of those pathogens. A better understanding of these lectins may yield information about how pathogens are captured by particular cells and how they spread in different tissues. These studies would provide more detail about the physiopathological mechanisms of viral and bacterial infections and may also lead to new strategies to treat or prevent infections.

Introduction: It has been reported that environmental factors such as hypoxia could contribute to the pathogenesis of Alzheimer's disease (AD). Therapeutics like hyperbaric oxygen treatment, which improves tissue oxygen supply and ameliorates hypoxic conditions in the brain, may be an alternative therapy for AD and amnestic mild cognitive impairment (aMCI). The present work aims to investigate the potential therapeutic effect of hyperbaric oxygen treatment for AD and aMCI. Methods: We recruited 42 AD, 11 aMCI, and 30 control AD patients in this study. AD and aMCI patients were treated with 40 minutes of hyperbaric oxygen once a day for 20 days and assessed by neuropsychiatric assessments including Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Activities of Daily Living (ADL) scale before and at 1‐, 3‐, and 6‐month follow‐up after treatment. Control AD patients who were not given hyperbaric oxygen treatment had similar clinical profile as hyperbaric oxygen treated AD. We examined 10 of the AD/aMCI patients with fluorodeoxyglucose positron emission tomography. Results: In self‐comparison study, one course of hyperbaric oxygen treatment significantly improved the cognitive function assessed by MMSE and MoCA in AD patients after 1‐month follow‐up; such treatment also significantly improved MMSE score at 3‐month follow‐up and MoCA score at 1‐ and 3‐month follow‐up in aMCI patients. The ADL scale was significantly improved in AD patients after 1‐ and 3‐month follow‐up. Compared to the control AD patients, the MMSE and MoCA in hyperbaric oxygen treated AD patients were significantly improved after 1‐month follow‐up. Hyperbaric oxygen treatment also ameliorated the reduced brain glucose metabolism in some of the AD and aMCI patients. Conclusion: Based on previous studies and our recent findings, we propose that hyperbaric oxygen treatment may be a promising alternative therapy for AD and aMCI.