[Effects of telmisartan on the level of Aß1-42, interleukin-1ß, tumor necrosis factor α and cognition in hypertensive patients with Alzheimer's disease].

OBJECTIVE: To explore the effects of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator-activated receptor γ-stimulating activity, on the levels of Aß1-42, interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α) and cognition in elderly hypertensive patients with Alzheimer's disease (AD). METHODS: A total of 48 patients with probable AD and essential hypertension were randomly assigned into telmisartan group (n = 24, 40 - 80 mg qd) or amlodipine group (n = 24, 5 - 10 mg qd) for 6 months at Henan Provincial People's Hospital during 2008 - 2011. Cognitive evaluations were assessed at pre-treatment and 24 weeks post-treatment by clinical assessment, rating scales and neuropsychological tests while the cerebrospinal fluid (CSF) levels of Aß1-42, IL-1ß and TNF-α by enzyme-linked immunosorbent assay (ELISA). RESULTS: After 6 months, mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) significantly decreased compared with baseline values to a similar extent in both groups. No significant differences existed between two groups in SBP or DBP. The patients displayed significantly higher Aß1-42 and greatly lower levels of IL-1ß and TNF-α in the telmisartan group versus the amlodipine group (P < 0.05). At 24 weeks, the patients in the telmisartan group had better mini-mental state examination (MMSE) (22.0 ± 3.4) and Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) (15 ± 5) scales scores than those taking amlodipine (MMSE (19.5 ± 2.8) and ADAS-cog (18 ± 5). Patients treated with telmisartan had better improvement on the MMSE (P < 0.05) and ADAS-cog (P < 0.05) scales compared with the amlodipine group by the end of study week 24. CONCLUSION: Telmisartan may delay the decreased level of Aß1-42 and reduce the levels IL-1ß and TNF-α in CSF so as to improve the cognitive function of elderly hypertensive patients with AD. With additional benefits in comparison with common antihypertensive drugs, it may offer a novel therapeutic strategy of AD.

[Clinical rehabilitative effect of memantine on cognitive and motor disorders in patients with Parkinson's disease].

OBJECTIVE: To study the effects of memantine on cognitive and motor impairment in patients with Parkinson's disease (PD). METHODS: A total of 55 PD patients complicated by varying degrees of cognitive impairment were randomly divided into two groups. The patients of experimental group (n = 28) received memantine (20 mg/d) while those in the control group (n = 27) conventional antiparkinsonian drug therapy alone. The cognitive and motor evaluations were assessed at pre-treatment and 12, 24 weeks post-treatment by clinical assessment, rating scales and neuropsychological tests. RESULTS: At week 24 the patients in the memantine group had better MMSE (22.8 ± 1.8), ADAS-cog (18.6 ± 2.3), and UPDRS-III (34.6 ± 4.2) scales scores than those taking placebo MMSE (18.5 ± 1.7), ADAS-cog (21.9 ± 2.4), and UPDRS-III (41.2 ± 4.0). Patients treated with memantine had better improvement on the MMSE (P < 0.05), ADAS-cog (P < 0.05), and UPDRS-III (P < 0.05) scales compared with the control group by the end of study week 24. CONCLUSION: Memantine may improve the cognitive and motor impairments of PD. And it is both safe and well-tolerated.

[Effects of ß-amyloid-induced microglial inflammatory supernatant on neuronal apoptosis].

OBJECTIVE: To study the effects of neuronal apoptosis under the induction of ß-amyloid inflammatory supernatant. METHODS: The neurons were intervened by ß-amyloid-induced inflammatory supernatant at the concentration of Aß1-42 at 125 nmol/L. And the expressions of Bcl-2, caspase-3, PARP and neuronal apoptosis were detected. RESULTS: The caspase-3 (14.2 ± 1.8), Bcl-2 (10.6 ± 0.8) positive cells of microglia inflammatory supernatant stimulated group were significantly elevated than the control (2.2 ± 0.6, 5.0 ± 0.3, P < 0.01). Nuclear chromatin was uniform yellow-green fluorescent. And there was significant difference of neuronal apoptosis between microglia inflammatory supernatant group and Aß1-42 directly stimulated group. CONCLUSION: Neuronal apoptosis is induced by caspase-3 in ß-amyloid inflammatory supernatant. One of the important causes is chronic inflammatory process of activated microglia by Aß.

Inhibition of tau hyperphosphorylation and beta amyloid production in rat brain by oral administration of atorvastatin.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder and the leading cause of dementia in the elderly. The two hallmark lesions in AD brain are deposition of amyloid plaques and neurofibrillary tangles (NFTs). Hypercholesteremia is one of the risk factors of AD. But its role in the pathogenesis of AD is largely unknown. The aim of this study was to investigate the relationship between hypercholesteremia and tau phosphorylation or beta-amyloid (Abeta), and evaluate the effect of atorvastatin on the level of tau phosphorylation and Abeta in the brains of rats fed with high cholesterol diet. METHODS: Sprague-Dawley (SD) rats were randomly divided into normal diet control group, high cholesterol diet group, and high cholesterol diet plus atorvastatin (Lipitor, 15 mg x kg(-1) x d(-1)) treated group. Blood from caudal vein was collected to measure total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high-density lipoprotein (HDL) at the end of the 3rd and the 6th months by an enzymatic method. The animals were sacrificed 6 months later and brains were removed. All left brain hemispheres were fixed for immunohistochemistry. Hippocampus and cerebral cortex were separated from right hemispheres and homogenized separately. Tau phosphorylation and Abeta in the brain tissue were determined by Western blotting (using antibodies PHF-1 and Tau-1) and anti-Abeta40/anti-Abeta42, respectively. RESULTS: We found that high cholesterol diet led to hypercholesteremia of rats as well as hyperphosphorylation of tau and increased Abeta level in the brains. Treatment of the high cholesterol diet fed rats with atorvastatin prevented the changes of both tau phosphorylation and Abeta level induced by high cholesterol diet. CONCLUSIONS: Hypercholesteremia could induce tau hyperphosphorylation and Abeta production in rat brain. Atorvastatin could inhibit tau hyperphosphorylation and decrease Abeta generation. It may play a protective role in the patho-process of hypercholesteremia-induced neurodegeneration in the brain.

[Effects of estrogen on P-Tau, ChAT and nerve growth factor protein expressions in the brain tissue of rats with Alzheimer's disease].

OBJECTIVE: To examine the effect of estrogen on the expressions of phosphorylated Tau (P-Tau), ChAT and nerve growth factor (NGF) protein in the brain tissue of rat models of Alzheimer disease (AD). METHODS: Rat models of AD were established by injecting Aß1-42 protein fragments in the right lateral ventricle. Two weeks later, 17ß-estradiol tablets were implanted subcutaneously at the neck of the rats and maintained for 30 days. The pathological changes in the rats' brain neurons and alterations in the expressions of P-Tau, ChAT and NGF proteins were observed using HE staining and immunohistochemistry, respectively. RESULTS: In the AD rats, neurofibrillary tangles occurred in the brain tissue, and estrogen treatment significantly reduced the formation of neurofibrillary tangles. Estrogen treatment also resulted in lowered P-Tau expression and increased ChAT and NGF protein expressions in comparison with those in the AD model rats. CONCLUSION: Estrogen can up-regulate ChAT and NGF and down-regulate tau protein expression, thus producing obvious therapeutic effect on AD in rats.