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Barry Cobb posted an update 6 months, 3 weeks ago
Moreover, the VDAC1-AKT (protein kinaseB)-GSK3β (glycogen synthase kinase 3 beta)-VDAC1 signaling pathway was abnormally activated in the hippocampus of APP/PS1 mice after noise exposure.
Chronic noise exposure and APP/PS1 overexpression may synergistically exacerbate cognitive impairment and neuropathological changes that occur in AD. This interaction may be mediated by the positive feedback loop of the VDAC1-AKT-GSK3β-VDAC1 signaling pathway.
Chronic noise exposure and APP/PS1 overexpression may synergistically exacerbate cognitive impairment and neuropathological changes that occur in AD. This interaction may be mediated by the positive feedback loop of the VDAC1-AKT-GSK3β-VDAC1 signaling pathway.
APOE ε4 is the best-known risk factor for late-onset Alzheimer’s disease (AD). Population studies have demonstrated a relatively low prevalence of APOE ε4 among Chinese population, implying additional risk factors that are Chinese-specific may exist. Apart from ε-alleles, genetic variation profile along the full-length APOE has rarely been investigated.
In this study, we filled this gap by comprehensively determining all genetic variations in APOE and investigated their potential associations with late-onset AD and mild cognitive impairment (MCI) in southern Chinese.
Two hundred and fifty-seven southern Chinese participants were recruited, of whom 69 were AD patients, 83 had MCI, and 105 were normal controls. Full-length APOE from promoter to 3’UTR regions were sequenced. Genetic variants were identified and compared among the three groups.
While APOEε4 was more significantly found in AD patients, the prevalence of APOE ε4 in southern Chinese AD patients was the lowest when compared to other areas of China and nearby regions, as well as other countries worldwide. We further identified 13 rare non-singleton variants in APOE. selleck screening library Significantly more AD patients carried any of the rare non-singleton variants than MCI and normal subjects. Such difference was observed in the non-carriers of ε4-allele only. Among the identified rare variants, the potential functional impact was predicted for rs532314089, rs553874843, rs533904656 and rs370594287.
Our study suggests an ethnic difference in genetic risk composition of AD in southern Chinese. Rare variants on APOE are a potential candidate for AD risk stratification biomarker in addition to APOE-ε4.
Our study suggests an ethnic difference in genetic risk composition of AD in southern Chinese. Rare variants on APOE are a potential candidate for AD risk stratification biomarker in addition to APOE-ε4.
In a previous study on Alzheimer’s disease (AD), we showed that vestibular dysfunction derived from cerebral disorders contributes to balance disorders. No previous clinical study has attempted to prevent the progression of balance disorders in dementia patients through vestibular stimulation using an air caloric device.
The purpose of this pilot study was to delay the progression of balance disorders by inducing vestibular compensation, specifically by utilizing the effect of vestibular stimulation to activate the cerebrum.
Fifteen individuals were randomized and classified into a stimulation group or a nonstimulation group. Eight AD patients underwent vestibular stimulation every 2 weeks for 6 months in the stimulation group. Seven AD patients participated in the nonstimulation group (the control group). Both groups were subsequently evaluated using a Mini-Mental State Examination (MMSE), stepping test, caloric test, and smooth pursuit eye movement test just before starting the study and 6 months latet vestibular stimulation by air caloric device is safe and tolerable in patients with AD.
As a potential brain imaging biomarker, amplitude of low frequency fluc-tuation (ALFF) has been used as a feature to distinguish patients with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) from normal controls (NC). However, it remains unclear whether the frequency-dependent pattern of ALFF alterations can effectively distinguish the different phases of the disease.
In the present study, 52 AD and 50 aMCI patients were enrolled together with 43 NC in total. The ALFF values were calculated in the following three frequency bands classical (0.01-0.08 Hz), slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz) for the three different groups. Subsequently, the local functional abnormalities were employed as features to examine the effect of classification among AD, aMCI and NC using a support vector machine (SVM).
We found that the among-group differences of ALFF in the different frequency bands were mainly located in the left hippocampus (HP), right HP, bilateral posterior cingulate cortex (PCC) and bilateral precuneus (PCu), left angular gyrus (AG) and left medial prefrontal cortex (mPFC). When the local functional abnormalities were employed as features, we identified that the ALFF in the slow-5 frequency band showed the highest accuracy to distinguish among the three groups.
These findings may deepen our understanding of the pathogenesis of AD and suggest that slow-5 frequency band may be helpful to explore the pathogenesis and distinguish the phases of this disease.
These findings may deepen our understanding of the pathogenesis of AD and suggest that slow-5 frequency band may be helpful to explore the pathogenesis and distinguish the phases of this disease.
White matter (WM) beta-amyloid uptake has been used as a reference region to calculate the cortical standard uptake value ratio (SUVr). However, white matter hyperintensities (WMH) may have an influence on WM beta-amyloid uptake. Our study aimed to investigate the associations between WMH and WM beta-amyloid deposition in cognitively unimpaired elderly.
Data from 83 cognitively unimpaired individuals in the Alzheimer’s Disease Neuroimag- ing Initiative (ADNI) dataset were analyzed. All participants had complete baseline and four-year follow-up information about WMH volume, WM 18F-AV-45 SUVr, and cognitive function, includ- ing ADNI-Memory (ADNI-Mem) and ADNI-Executive function (ADNI-EF) scores. Cross-sectional and longitudinal linear regression analyses were used to determine the associations between WMH and WM SUVr and cognitive measures.
Lower WM 18F-AV-45 SUVr at baseline was associated with younger age (β=0.01, P=0.037) and larger WMH volume (β=-0.049, P=0.048). The longitudinal analysis found an annual increase in WM 18F-AV-45 SUVr was associated with an annual decrease in WMH volume (β=-0.