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Wang H.-L.,Hebei Medical University | Wang Y.-Y.,Hebei Medical University | Liu X.-G.,Jingxing Hospital | Kuo S.-H.,Columbia University | And 4 more authors.
Journal of Alzheimer's Disease | Year: 2016

Abnormal cholesterol metabolism is an established feature of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) is the fluid surrounding the central nervous system, and the protein and lipid content alterations in the CSF could be biomarkers for degenerative changes in the brain. The laboratory diagnosis of AD is limited to the analysis of three biomarkers in CSF: Aβ42, total tau, and phospho-tau. The purpose of this analysis is to systematically analyze the available data describing the biomarkers of cholesterol and its metabolites in the CSF of subjects with AD. MEDLINE, EMBASE, and the Cochrane Central database were systematically queried to collect studies that have evaluated the markers of cholesterol and its metabolites in the CSF of subjects with mild cognitive impairment (MCI) or AD and age-matched controls. Analysis of the published data shows that the levels of cholesterol are increased in MCI subjects; 24-hydroxycholesterol and 27-hydroxycholesterol are elevated in AD and MCI subjects compared to controls. There is a significant dysfunction of cholesterol metabolism in the CSF of AD subjects. This analysis indicates that in addition to the available biomarkers in the CSF, such as Aβ42, total tau, and phospho-tau, 24-hydroxycholesterol, 27-hydroxycholesterol, and cholesterol appear to be sensitive biomarkers for the evaluation of MCI and AD. © 2016 - IOS Press and the authors. All rights reserved. Source

Wang H.,Hebei Medical University | Lian K.,Hebei Medical University | Han B.,Hebei Medical University | Wang Y.,Hebei Medical University | And 6 more authors.
Journal of Alzheimer's Disease | Year: 2014

Alzheimer's disease (AD), the most common age-dependent neurodegenerative disorder, produces a progressive decline in cognitive function. The metabolic mechanism of AD has emerged in recent years. In this study, we used multivariate analyses of gas chromatography-mass spectrometry measurements to determine that learning and retention-related metabolic profiles are altered during aging in the hippocampus of the senescence-accelerated mouse prone 8 (SAMP8). Alterations in 17 metabolites were detected in mature and aged mice compared to young mice (13 decreased and 4 increased metabolites), including metabolites related to dysfunctional lipid metabolism (significantly increased cholesterol, oleic acid, and phosphoglyceride levels), decreased amino acid (alanine, serine, glycine, aspartic acid, glutamate, and gamma-aminobutyric acid), and energy-related metabolite levels (malic acid, butanedioic acid, fumaric acid, and citric acid), and other altered metabolites (increased N-acetyl-aspartic acid and decreased pyroglutamic acid, urea, and lactic acid) in the hippocampus. All of these alterations indicated that the metabolic mechanisms of age-related cognitive impairment in SAMP8 mice were related to multiple pathways and networks. Lipid metabolism, especially cholesterol metabolism, appears to play a distinct role in the hippocampus in AD. © 2014-IOS Press and the authors. All rights reserved. Source

Cui H.-X.,Hebei Medical University | Cui H.-X.,Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province | Xie G.-S.,Hebei Medical University | Li S.,Hebei Medical University | And 5 more authors.
Acta Anatomica Sinica | Year: 2010

Objective: To explore the effects of dihydrostestosterone (DHT) on synaptic plasticity and the expression of N-methyl-D-aspartate receptor 1(NMDAR1) in CA1 region of hippocampus in senescence accelerated mouse prone strain 8 (SAMP8). Methods: Twenty-one 6-month-old male SAMP8 were randomly divided into sham-operation control group, castrated group and DHT replacement therapy after castration group(7 in each group). The dose of DHT was 1mg/(kg·d) . Twenty-one days later, the apical dendritic thorns density in hippocampal CA1 region was observed with Golgi staining method. Immunohistochemical method and computer pathological image analysis system were used to determine the expression of synaptophysin and N-methyl-D-aspartate 1 (NMDAR1) in hippocampal CA1 region. Results: 1. In the Golgi staining, the number of the apical dendritic thorns density of hippocampal CA1 region of castrated group decreased. However, DHT replacement therapy could significantly increase the apical dendritic thorns density (P < 0.05). 2. The expressions of synaptophysin and NMDAR1 in the hippocampal CA1 region of castrated group decreased markedly. The average absorbance (AA) values were sharply lower than those of other groups (P < 0.05). DHT replacement therapy could obviously increase the expression of synaptophysin and NMDAR1 in the hippocampal CA1 region. Conclusion: DHT replacement therapy can increase the density of dendritic thorns and modulate synaptic plasticity of hippocampal CA1 region. DHT may potentially affect hippocampal synaptic plasticity by modulating pyramidal cell NMDAR1. Source

Wang H.,Hebei Medical University | Geng Y.,Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province | Han B.,Hebei Medical University | Qiang J.,Hebei Medical University | And 5 more authors.
PLoS ONE | Year: 2013

Chronic high-frequency repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique that has recently received increasing interests as a therapeutic procedure for neurodegenerative diseases. To identify the metabolism mechanism underlying the improving effects of rTMS, we observed that high frequency (25Hz) rTMS for 14 days could reverse the decline of the performance of the passive avoidance task in aged mice. We further investigated the metabolite profiles in the prefrontal cortex (PFC) in those mice and found that rTMS could also reverse the metabolic abnormalities of gamma-aminobutyric acid, N-acetyl aspartic, and cholesterol levels to the degree similar to the young mice. These data suggested that the rTMS could ameliorate the age-related cognitive impairment and improving the metabolic profiles in PFC, and potentially can be used to improve cognitive decline in the elderly. © 2013 Wang et al. Source

Xu S.,Hebei Medical University | Xu S.,Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province | Xie B.,Hebei Medical University | Xie B.,Brain Aging and Cognitive Neuroscience Laboratory of Hebei Province | And 14 more authors.
Neuroepidemiology | Year: 2014

Background: Mild cognitive impairment (MCI) has been suggested as a term for a boundary area between normal aging and dementia. This study was designed to determine the prevalence of MCI in the elderly in the Hebei province, China, and explore its related factors. Methods: Participants included 2,601 community-dwelling people aged 60 years or older who resided in the four major cities of the Hebei province. In stage 1 of the study, the Mini-Mental State Examination and the Montreal Cognitive Assessment were administered for screening purposes. In stage 2, the subjects who screened positive were further examined by neurologists. The diagnosis of MCI was made according to Petersen's criteria. Results: The estimated prevalence of MCI was 21.3%. MCI was more prevalent at age 65-69 (28.3%), and its overall rates among men (24.1%) were higher than those of women (19.9%). The higher prevalence of MCI was associated with very old age (≥80 years old; OR = 2.457, 95% CI = 1.471-4.104), male gender (OR = 1.363, 95% CI = 1.097-1.694), low education level (OR = 2.439, 95% CI = 1.623-3.663), and poor economic status (OR = 2.882, 95% CI = 1.949-4.255). Conclusions: Our findings show a high prevalence of MCI in the elderly urban population in the Hebei province. Gender, education level, and economic status may have an important role in the etiology of MCI. © 2014 S. Karger AG, Basel. Source

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