Molecular Insights into Tau Pathology and its Therapeutic Strategies in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of dementia. The two major hallmarks of this disease are extracellular amyloid plaques and intracellular neurofibrillary tangles in the brain, accompanied by loss of neurons and synapses. The plaques and tangles mainly consist of amyloid-β (Aβ) and tau protein, respectively.

Blood and CSF chemokines in Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.

Objective: Chemokines, which are chemotactic inflammatory mediators involved in controlling the migration and residence of all immune cells, are closely associated with brain inflammation, recognized as one of the potential processes/mechanisms associated with cognitive impairment. We aim to determine the chemokines which are significantly altered in Alzheimer's disease (AD) and mild cognitive impairment (MCI), as well as the respective effect sizes, by performing a meta-analysis of chemokines in cerebrospinal fluid (CSF) and blood (plasma or serum).

Methods: We searched three databases (Pubmed, EMBASE and Cochrane library) for studies regarding chemokines.

Effect of antioxidant intake patterns on risks of dementia and cognitive decline.

Background: Previous studies have suggested that increased antioxidant intakes might reduce risk of cognitive disorders including Alzheimer's disease (AD). Which avenue of antioxidant intake (vitamin E/C) is more effective for decreasing risk, however, is largely unknown.

Objectives: To quantitatively investigate the relationships between the pattern of antioxidant intakes and risks of dementia and cognitive decline.

Blood and CSF Homocysteine Levels in Alzheimer's Disease: A Meta-Analysis and Meta-Regression of Case-Control Studies.

Objective: Hyperhomocysteinemia (HHcy), as an important risk factor for Alzheimer's disease (AD), would aggravate cognitive dysfunction. This study aimed to investigate whether and to what degree the homocysteine (Hcy) levels in blood and cerebrospinal fluid (CSF) were elevated in AD patients compared with healthy controls and to explore the factors related to the elevated Hcy levels in AD patients.

Methods: PubMed and Embase databases were searched to identify eligible studies, and study quality was evaluated using the Newcastle-Ottawa Quality Assessment Scale.

Hyperhomocysteinemia and risk of incident cognitive outcomes: An updated dose-response meta-analysis of prospective cohort studies.

Objective: This study aimed to comprehensively assess the dose-response relationship between blood homocysteine levels and risk of all cause, Alzheimer and vascular dementia, as well as cognitive impairment without dementia (CIND).

Method: We searched for all related prospective cohort studies reporting homocysteine as an exposure from patients with cognitive disorders as a result in the PubMed and EMBASE databases up to June 18, 2018. Pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) were extracted.

Effects of Gender and Other Confounding Factors on Leptin Concentrations in Alzheimer's Disease: Evidence from the Combined Analysis of 27 Case-Control Studies.

Leptin, as a link between fat mass and the brain, has been reported to be associated with gender. The gender differences in leptin levels between Alzheimer's disease (AD) and healthy elderly controls are inconclusive so far. To quantitatively summarize the leptin data available from female and male patients with AD, we searched PubMed and EMBASE for articles published from inception to July 20, 2017.

The associations between the MAPT polymorphisms and Alzheimer's disease risk: a meta-analysis.

Published studies revealed that the microtubule-associated protein tau (MAPT) gene polymorphisms increased Alzheimer's disease (AD) risk; the associations of 4 single nucleotide polymorphisms (SNPs, rs242557G/A, rs2471738C/T, rs3785883G/A and rs1467967A/G) of the MAPT gene with AD risk, however, remain inconclusive. Here, we conducted a meta-analysis to investigate the relationship between the MAPT SNPs and AD risk. A significant association of SNP rs242557 with AD risk was found in a dominant [odds ratio (OR) = 1.

The bridging integrator 1 Gene rs7561528 polymorphism contributes to Alzheimer's disease susceptibility in East Asian and Caucasian populations.

Genetic variants of the bridging integrator 1 (BIN1) at the rs7561528 single nucleotide polymorphism were implicated in increased risk of Alzheimer's disease in several case-control association studies. However, the studies have reported apparently conflicting results. Here, we searched the PubMed and Google Scholar databases.

[Research progress of abnormal phosphorylation of microtubule-associated tau protein and of the targeted inhibition of the phosphorylation].

Progressive dementia is described as the first and most prominent symptom of Alzheimer's disease (AD), and hyperphosphorylation of microtubule associated Tau protein (MAPT) plays a key role in neurodegeneration and neuronal dysfunction in AD and other neurodegenerative diseases. This paper reviews several protein kinases and phosphatases which can phosphorylate/dephosphorylate Tau protein, and evaluates a therapeutic strategy based on targeted inhibition of Tau kinases and activation of Tau phosphatases.

Luteolin reduces zinc-induced tau phosphorylation at Ser262/356 in an ROS-dependent manner in SH-SY5Y cells.

In brain, excess zinc alters the metabolism of amyloid precursor protein, leading to β-amyloid protein deposition, one of the hallmarks of Alzheimer's disease (AD) pathology. Recently, it has been reported that zinc accelerates in vitro tau fibrillization, another hallmark of AD. In the current study, we examined the effect of high-concentration zinc on tau phosphorylation in human neuroblastoma SH-SY5Y cells.

Luteolin protects against reactive oxygen species-mediated cell death induced by zinc toxicity via the PI3K-Akt-NF-κB-ERK-dependent pathway.

Zinc ion elevation contributes to acute excitotoxic brain injury and correlates with the severity of dementia in chronic neurodegenerative diseases. Downstream control of zinc-triggered signals is believed to be an efficient countermeasure. In the current study, we examined whether the flavonoid luteolin (Lu) could protect human neuroblastoma SH-SY5Y cells against zinc toxicity.

[Newest research progress in hypoxia genetic adaptation to high altitude].

The genetic adaptation of Plateau residents to hypoxia of low-pressure has been the hot spot for study. In terms of physiology, the adaptation involves the regulation responses of blood vessels, the changes in blood cells, antioxidant capacity and energy metabolism, as well as the hypoxia-induced changes in nuclear transcription. Physiological adaptation is heritable, so people who have already adapted themselves to high altitude are bound to be different, in regard to gene level, from the crowd who have not yet adapted themselves to high altitude environment.

[An analysis of physiological load intensity in the course of track and field studies offered in general colleges].

This investigation was directed to the physiological load intensity in the curricula of track and field studies offered in 8 general colleges. We adopted the sampling survey method and monitored the heart rate of 80 first-year students who were from different grades in 8 colleges and were attending the track and field class. The data collected from these male student show: (1) The pre-exercise heart rate is 80 per minute; the first inflection point appears at 28 minutes after exercise; the heart rate is 132 per minute and the slope is -0.