Rey Yue Yuan

Proteomic Identification of Lower Apolipoprotein A-I in Alzheimer’s Disease

Many researches have been trying to find the potential biomarkers for Alzheimer’s disease (AD). We hereby used the proteomics method to search for protein expression differences in the serum between AD patients and controls. We enrolled 59 AD patients and 74 age- and sex-matched controls in this study. Ten AD patients and 10 controls were selected for proteomic analysis. Apolipoprotein A-I (ApoA-I) was found to have a lower expression in the AD group by a proteomics two-dimensional gel electrophoresis study. We further measured the serum ApoA-I level which was significantly lower in the AD patients (112.29 ± 21.33 mg/dl) in comparison to the controls (144.53 ± 19.91 mg/dl; p < 0.0002). Lower serum ApoA-I levels might be a potential biomarker for AD.

Methylenetetrahydrofolate reductase polymorphisms and plasma homocysteine in levodopa-treated and non-treated Parkinson's disease patients

Genetic C677T and A1298C polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR) and levodopa therapy in Parkinsons disease (PD) may increase homocysteine (Hcy) level. We examined whether connecting both polymorphisms influences the effect of levodopa on Hcy. MTHFR genotypes and Hcy, vitamin B(12), and folate levels were determined in 48 levodopa-treated PD patients (PD-L), 28 non-treated PD patients (PD-N) and 110 controls. Hcy was remarkably higher in PD-L than in PD-N and controls (p<0.001); similarly, the differences were seen in different age subgroups and in both genders. Furthermore, Hcy differences between PD-L and PD-N were evident in 677C/T, T/T, C/T + A/A, T/T + A/A (all p<0.05), and 1298A/A (p<0.001), but not in others such as 677C/C, and C/C + A/A. Hcy in PD-N and controls was comparable for all genotypes. In PD-L, Hcy was the highest in 677T/T, then in C/T, and in C/C with a significant difference from T/T (p=0.014), but was not different among A1298C genotypes. Likewise, Hcy was the highest in 677T/T+1298A/A, intermediate in C/T+A/A, and the lowest in C/C+A/A. In PD-N, Hcy was similar among all genotypes. In conclusion, Hcy elevation may be caused by levodopa administration, and further promoted by 677C/T and T/T, but not by A1298C genotypes. The promoting elevation in 1298A/A is attributed to combining the 677T allele. Neither C677T nor A1298C genotypes contribute to elevating Hcy in PD-N.

Brain Single Photon Emission Computed Tomography in Patients with A3243G Mutation in Mitochondrial DNA tRNA

Abstract: Brain single photon emission computed tomography (SPECT) studies were conducted in three patients with A3243G mutation of the mitochondrial (mt) DNA tRNA. All were born to mothers suffering from chronic progressive external ophthalmoplegia (CPEO) with the same A3243G point mutation of the mtDNA tRNA. The first case manifested clinically with MELAS, the second case manifested with CPEO, and third case was characterized by recurrent migraine‐like headache, tremor, and epilepsy. Brain SPECT of all patients, regardless of whether they had or had not suffered from stroke‐like episodes, showed multiple areas of asymmetrical decreased perfusion, particularly in the posterior and lateral head regions, especially the temporal lobes. Crossed‐cerebellar diaschisis may occur. Conventional brain magnetic resonance images failed to show some of the lesions. Decreased regional cerebral blood flow, rather than previously proposed hyperemia, is likely to be the cause. We conclude that mitochondrial vasculopathy with regional cerebral hypoperfusion may be seen on brain SPECT in patients with mitochondrial disorders and A3243G mutations, regardless of whether they have or have not suffered from stroke‐like episodes.

Low Sleep Efficiency in Patients with Cognitive Impairment

Alzheimers disease (AD) is the most common cause of dementias. Mild cognitive impairment (MCI) indicates the situation that a person has memory complaints and mild objective cognitive impairment but no evidence of dementia. Sleep disturbance, one of the behavioral and psychological symptoms of dementia (BPSD), frequently occurs in patients with AD or MCI. The alteration of sleep architectures in AD patients remains inconclusive. In this study, we conducted the polysomnography. (PSG) examination among patients with mild AD with cholinesterase inhibitors (N=10) or MCI (N=12) and age-matched nondemented controls (N=13). The results showed sleep efficiency, which was one of the important parameters for sleep quality was significantly lower in patients with MCI and AD (N=22), 79.14 +/- 11.06 % vs. 67.07 +/- 19.10 %, p=0.046. There were no statistic differences of sleep architecture but a trend of REM insufficiency in patients with MCI or AD. The mean scores of geriatric depression score (GDS) and Epworth sleepiness scale (ESS) did not differ among the three groups. Our study implicated maintenance of sleep was impaired in patients with cognitive impairment and it was independent with depressive symptoms.

Neuromagnetic SII responses do not fully reflect pain scale

To elucidate the role of somatosensory cortices in coding pain magnitude, we recorded the neuromagnetic responses of ten subjects to mild, moderate, and severe pain stimulation by delivering thulium-laser pulses on the dorsum of the left hand. The stimulus intensities for producing different pain levels were determined individually, and the mean values across subjects were 255, 365, and 490 mJ for mild, moderate, and severe pain, respectively. We obtained 40 responses for each intensity condition, and analyzed the averaged cortical signals by multi-dipole modeling. All subjects showed consistent activation over the bilateral secondary somatosensory (SII) cortices for each intensity level, peaking around 150-230 ms, with 15-ms earlier on the contralateral hemisphere. The SII dipole strength was significantly larger for the moderate than for the mild pain stimulation, but lacked further increase as the pain magnitude elevated to the severe level. In contrast, the primary somatosensory cortical response was detected in only half of our subjects, and thus it seemed difficult to evaluate its role in pain intensity coding. Our results suggest that activation strength in human SII cortices reflects the magnitude of peripheral noxious inputs only up to the moderate level, and some other cerebral correlates may get involved in sensing a further increment of pain magnitude.

Increase of toll-like receptor 4 but decrease of interleukin-8 mRNA expression among ischemic stroke patients under aspirin treatment.

OBJECTIVES Toll-like receptors (TLRs) are molecules conserved in evolution for detecting pathogen invasions and tissue damage and are involved in atherogenesis. This study explores the mRNA expression of TLRs and their probable role in further disease occurrence among ischemic stroke patients. DESIGN AND METHODS A total of 89 ischemic stroke patients and 166 controls were recruited for this study. Total RNA was extracted and mRNA was reverse-transcribed to cDNA and was analyzed for TLRs and interleukin 8 (IL8). RESULTS The TLR4 mRNA expression level is significantly higher in the stroke group. Conversely, IL-8 mRNA levels decreased significantly in the patient group. CONCLUSION Our results suggest that TLR4 overexpression in mRNA levels is observed in stroke patients, which might account for the probable inflammatory injury before or after stroke. A reduction of IL-8 expression could result from the downregulatory effects of aspirin.

Zebrafish cyclin Dx is required for development of motor neuron progenitors, and its expression is regulated by hypoxia-inducible factor 2α.

Cyclins play a central role in cell-cycle regulation; in mammals, the D family of cyclins consists of cyclin D1, D2, and D3. In Xenopus, only homologs of cyclins D1 and D2 have been reported, while a novel cyclin, cyclin Dx (ccndx), was found to be required for the maintenance of motor neuron progenitors during embryogenesis. It remains unknown whether zebrafish possess cyclin D3 or cyclin Dx. In this study, we identified a zebrafish ccndx gene encoding a protein which can form a complex with Cdk4. Through whole-mount in situ hybridization, we observed that zccndx mRNA is expressed in the motor neurons of hindbrain and spinal cord during development. Analysis of a 4-kb promoter sequence of the zccndx gene revealed the presence of HRE sites, which can be regulated by HIF2α. Morpholino knockdown of zebrafish Hif2α and cyclin Dx resulted in the abolishment of isl1 and oligo2 expression in the precursors of motor neurons, and also disrupted axon growth. Overexpression of cyclin Dx mRNA in Hif2α morphants partially rescued zccndx expression. Taken together, our data indicate that zebrafish cyclin Dx plays a role in maintaining the precursors of motor neurons.