Weak central coherence in patients with Alzheimer’s disease

Central coherence refers to the ability to interpret details of information into a whole. To date, the concept of central coherence is mainly used in research of autism, Asperger＇s syndrome and recently in the research on eating disorders. The main purpose of the present study was to examine central coherence in patients with Alzheimer＇s disease. Nine Alzheimer＇s disease patients and ten age- and gender-matched control subjects, who differed significantly in neurological assessment, were shown a picture of a fire. Compared to control subjects, the Alzheimer＇s disease patients described the picture in a fragmented way by mentioning details and separate objects without perceiving the context of the fire. In conclusion, patients with Alzheimer＇s disease are at the weak end of central coherence, and hence suffer from a fragmented view of their surroundings. The findings have important clinical implications for the understanding of patients with Alzheimer＇s diseaseand also for the possibility of caregivers to meet the Alzheimer＇s disease individual in an appropriate way in the everyday care.

Protective effects of Lingguizhugan decoction on amyloid-beta peptide (25-35)-induced cell injury Anti-inflammatory effects

In the present study, a human neuroblastoma cell line （SH-SY5Y） and BV-2 microglia were treated with amyloid-β peptide （25-35）, as a model of Alzheimer＇s disease, to evaluate the protective effects of 10-3-10-8 g/mL Lingguizhugan decoction and to examine the underlying anti-inflammatory mechanism. Lingguizhugan decoction significantly enhanced the viability of SH-SY5Y cells with amyloid-β peptide-induced injury, and lowered levels of interleukin-1β, interleukin-6, tumor necrosis factor-a and nitric oxide in the culture supernatant of activated BV-2 microglia. The effects of 103 g/mL Lingguizhugan decoction were more significant. These results suggest that Lingguizhugan decoction can protect SH-SY5Y cells against amyloid-β peptide （25-35）-induced injury in a dose-dependent manner by inhibiting overexpression of inflammatory factors by activated microglia.

Protective effect of tetrahydroxy stilbene glucoside on learning and memory by regulating synaptic plasticity

Damage to synaptic plasticity induced by neurotoxicity of amyloid-beta is regarded to be one of the pathological mechanisms of learning and memory disabilities in Alzheimer＇s disease patients. This study assumed that the damage of amyloid-beta to learning and memory abilities was strongly associated with the changes in the Fyn/N-methyl-D-aspartate receptor 2B （NR2B） expression. An APP695V7171 transgenic mouse model of Alzheimer＇s disease was used and treatment with tetrahydroxy-stilbene glucoside was administered intragas- trically. Results showed that intragastric administration of tetrahydroxy-stilbene glucoside improved the learning and memory abilities of the transgenic mice through increasing NR2B receptors and Fyn expression. It also reversed parameters for synaptic interface structure of gray type I. These findings indicate that tetrahydroxy stilbene glucoside has protective effects on the brain, and has prospects for its clinical application to improve the learning and memory abilities and treat Alzheimer＇s disease.

Pharmarcogenetic Mechanism of ACE liD Polymorphism Adversely Responding to ACE Inhibitors in Regulating the ACE Promoter Activity in Neurons

The ACE （angiotensin converting enzyme） inhibitors are not only drugs widely prescribed drugs in cardiovascular diseases, but also potentially therapeutic agents in dementia. Based on the findings that the ACE inhibitors could activate the c-Jun N-terminal kinase signal to increase the ACE gene expression and that the Alu element of the human ACE gene involved in regulating ACE promoter activity, we aimed to investigate whether there are different pharmacogenetic responses of ACE I/D polymorphism to the ACE inhibitors in neurons. The three reporter vectors, pACEpro（0-SEAP, p-I-ACEpro-SEAP, and p-D-ACEpro-SEAP were used to examine the transcriptional activity of the vectors responding to the lisinopril treatment using a transient-transfection method in SH-SY5Y cells. Our results showed that lisinopril increased the promoter activity of an ACE gene by 16.7%. Additionally, we found the lisinopril enhanced the ACE promoter activity of the I-form vector by 17.2%, but adversely reduced that of the D-form vector by 16.8%, as compared with the respective control without the lisinopril treatment. Firstly, our findings had proved that the UD polymorphism of ACE gene contrarily responds to the ACE inhibitors in regulating the ACE expression in neurons, which provide a novel insight suggesting genetic testing to tailor the treatment regimens in AD （Alzheimer＇s disease） patients.

Scavenging Effect of Naoerkang(脑尔康) on Amyloid BetaPeptide Deposition in the Hippocampus in a Rat Model of Alzheimer's Disease

Objective： To observe the effect of a Chinese medicine compound, Naoerkang （脑尔康, NEK）, on amyloid-beta peptide （1-42; A 131-42） and matrix metalloproteinase-9 （MMP-9） expressions in the hippocampus of AIzheimer＇s disease （AD） model rats. Methods： A total of 48 male Sprague Dawley （SD） rats were randomly divided into normal control, untreated, and piracetam groups, and low-dose, medium-dose, and high-dose NEK groups, with 8 rats in each group. The 5-1μL aggregated Aβ1-42 （2μg/μL） were injected into both CA1 areas of the hippocampus in the rats to establish an AD model, whereas the normal control was treated with the same dose of normal saline. The rats in the NEK groups were treated with a high, medium, or low dose of NEK [60 g/（kg-d）, 30 g/（kg-d）, and 15 g/（kg.d）], respectively, intragastrically for 28 days; piracetam （0.375 g/kg, intragastrically） was consecutively administered in the piracetam group; and normal saline was applied in the normal control and untreated groups. A Y-maze test was used for behavioral study to test the learning and memory abilities. A 131-~ and MMP-9 expressions in the hippocampus was determined immunohistochemically, and the results were analyzed by image acquisition and an analysis system. Results： Aggregated A 131.42 induced obvious learning and memory dysfunction, as well as up-regulation of A 13 1-42 expression in the hippocampus. Compared with those in the normal control group, the learning and memory abilities of rats in the untreated group significantly decreased （P〈0.01）, and the expression of A β1-42 was significantly increased （P〈0.01）. Twenty-eight days after different treatments, compared with those in the untreated group, the learning and memory abilities of AD model rats in the piracetam, low-dose, medium-dose and high-dose NEK groups were significantly improved （P〈0.01 or P〈0.05）, and the expression of Aβ1-42 in the hippocampus decreased （P〈0.01 or P〈0.05）, and MMP-9 increased （P〈0.01 or P〈0.05）, especially in the high-dose NEK group. Conclusion： NEK might play a role of anti-dementia by increasing the expression of MMP-9 in the hippocampus of AD model rats, resulting in the reduction of the quantity of Aβ1.42 and improvement in learning and memory ability in AD model rats.

Influence of Electroacupuncture on COX Activity of Hippocampal Mitochondria in Senescence-accelerated Mouse Prone 8 Mice

Objective: To observe the effect of electroacupuncture(EA) on cytochrome c oxidase(COX) activity of hippocampal mitochondria in senescence-accelerated mouse prone 8(SAMP8) mice, and to explore the EA mechanism on Alzheimer disease(AD) in improving energy metabolic disorder. Methods: Twelve SAMP8 mice were randomly divided into a model group and an EA group, with six in each group. Six senescence-accelerated mouse resistance 1(SAMR1) mice were prepared as blank group. Mice in the EA group received EA on Baihui(GV 20) and Yongquan(KI 1), once a day for 7 d as a course, altogether 3 courses with one day interval between two courses. Mice in the model group and the blank group were manipulated and fixed as those in the EA group. After interventions, Morris water maze was employed to test spatial learning and memory ability to evaluate EA effect; spectrophotometry was used to detect the activity of hippocampal mitochondria COX. Results: Compared with the blank group, mean escape latencies of the EA group and model group were prolonged significantly in Morris water maze tests(P<0.01), the residue duration in the former platform quadrant significantly decreased(P<0.01). Compared with the model group, mean escape latencies on 1 d, 2 d and 3 d of the EA group were significantly reduced(P<0.05), and those on 4 d and 5 d continued the decreasing tendency(P<0.01), the residue duration on the former platform quadrant was significantly prolonged(P<0.05). The COX activity tests showed that, compared with the blank group, COX activities of the model group and the EA group were significantly decreased(P<0.01); compared with the model group, COX activity of the EA group was significantly elevated(P<0.01). Conclusion: It's plausible that EA improves AD learning and memory ability by increasing mitochondria COX activity, protecting the structure and function, and improving energy metabolism.