Alzheimer's disease (AD) is a multifactorial and heterogenic disorder. MiRNA is a class of non-coding RNAs with 19-22 nucleotides in length that can regulate the expression of target genes in the post-transcriptional level. It has been found that the miRNAome in AD patients is significantly altered in brain tissues, cerebrospinal fluid and blood circulation, as compared to healthy subjects. Experimental studies have suggested that expression changes in miRNA could drive AD onset and development via different mechanisms. Therefore, targeting miRNA expression to regulate the key genes involved in AD progression is anticipated to be a promising approach for AD prevention and treatment. Rodent AD models have demonstrated that targeting miRNAs could block biogenesis and toxicity of amyloid β, inhibit the production and hyper-phosphorylation of τ protein, prevent neuronal apoptosis and promote neurogenesis, maintain neural synaptic and calcium homeostasis, as well as mitigate neuroinflammation mediated by microglia. In addition, animal and human studies support the view that miRNAs are critical players contributing to the beneficial effects of cell therapy and lifestyle intervention to AD. This article reviews the most recent advances in the roles, mechanisms and applications of targeting miRNA in AD prevention and treatment based on rodent AD models and human intervention studies. The potential opportunities and challenges in clinical application of targeting miRNA for AD patients are also discussed.
Animals ; Humans ; MicroRNAs/genetics* ; Alzheimer Disease/prevention & control* ; Amyloid beta-Peptides ; Apoptosis ; Microglia

Alzheimer's disease(AD)is a central nervous system disease characterized by progressive cognitive dysfunction and memory loss.Increasing evidences suggest that β amyloid(Aβ)plays a critical role and may be a upstream molecule in AD pathogenesis involving both genetic and environmental factors.Aβ accumulation and its related inflammation are considered early events preceding neurodegeneration and neuronal loss in AD brain.However,all strategies and compounds targeting Aβ deposition have failed in clinical trials,implying complexity of AD pathogenesis.This article reviews Aβ hypothesis and its related mechanisms,pathophysiological process,and therapeutics of AD.
Alzheimer Disease ; pathology ; prevention & control ; therapy ; Amyloid beta-Peptides ; Brain ; physiopathology ; Humans

The Ministry of Science and ICT and the Ministry of Health and Welfare of the Republic of Korea have organized the first National Committee for Dementia Research, to which all domestic experts in the field have been invited as they endeavor to achieve ‘national dementia liability’, which is one of the core national agenda items of the current Korean government. To make this initiative sustainable and bring dementia under control, we should not focus only on providing care and economic support to the family of patients with dementia. Instead, a large-scale, long-term research and development (R&D) strategy for dementia prevention, diagnosis, and therapy is warranted. This R&D project comprises several parts: 1) elucidation of the etiology and prevention of dementia, 2) innovative diagnostics for dementia, 3) tailored therapies for dementia, and 4) tangible and effective care for dementia. Given the fact that dementia is a very heterogeneous condition involving multiple pathogenic factors and typically having a chronic disease course, comprehensive and integrated approaches across various disciplines should be explored for primary, secondary, and tertiary prevention of this disease. With the success of this R&D project, the national dementia liability system will gain momentum and come into its own. Integrated efforts in terms of both policyrelated and scientific initiatives would allow us to take a step closer to realizing our shared goal of living in a world of dementia carefree.
Alzheimer Disease ; Chronic Disease ; Dementia ; Diagnosis ; Humans ; Republic of Korea ; Tertiary Prevention

No abstract available.
Alzheimer Disease* ; Developing Countries* ; Primary Prevention*

OBJECTIVETo explore the potential effect of Guizhi plus Gegen Decoction (GGD) in improving learning and memory of lipopolysaccharides (LPS) induced neuroinflammatory mice and its possible mechanisms.

METHODSTotally 63 male ICR mice were randomly divided into 5 groups, i.e., the normal control (n = 13), the model group (n = 13), the low dose GGD group (n = 10), the high dose GGD group (n = 14), and the positive control group (n = 13). Mice were intraperitoneally injected with LPS (0.33 mg/kg) to induce Alzheimer's disease (AD) model. Mice in the high and the low dose GGD groups were administered with 12 g/kg or 6 g/kg by gastrogavage for 4 successive weeks. Mice in the control group were intraperitoneally injected with minocycline (50 mg/kg) for 3 days. By the end of treatment LPS were injected 4 h before behavior test each day, and then behavior test was conducted in mice of each group. Effect of GGD on learning and memory of AD mice was observed by using open field test, novel object recognition task, and Morris water maze.

RESULTSOpen field test showed there was no statistical difference in the movement time and the movement distance among all groups (P > 0.05), suggesting that LPS and GGD had no effect on locomotor activities of mice. In novel object recognition test, AD mice spent significantly shorter time to explore novel object after they were induced by LPS (P < 0.05), while for AD mice in the low and high dose GGD groups, their capacities for exploration and memory were significantly improved (P < 0. 05, P < 0.01). Results of Morris water maze showed that AD mice exhibited increased escape latency (P < 0.05) and spent much less time in swimming across the original platform (both P < 0.05). However, AD mice in the low and high dose GGD groups had obvious shortened latency and increased time percentage for swimming (P < 0.05, P < 0.01).

CONCLUSIONGGD possessed certain improvement in learning and memory disorder of LPS induced AD mice.

Alzheimer Disease ; chemically induced ; drug therapy ; psychology ; Animals ; Drugs, Chinese Herbal ; therapeutic use ; Lipopolysaccharides ; adverse effects ; Male ; Memory Disorders ; prevention & control ; Mice ; Mice, Inbred ICR ; Neuritis ; chemically induced ; drug therapy ; psychology ; Phytotherapy

Alzheimer's disease (AD) is the leading cause of dementia, and the most prevalent neurodegenerative disease in the elderly. The prevalence of AD is predicted to rise as life expectancy grows across populations. The exact cause of this devastating disease is still unknown; however, it is an aging-related multi-factorial disorder, and growing evidence supports the contribution of modifiable environmental factors to unmodifiable factors such as gene and ageing itself. The recent advancement of methodologies and techniques for early diagnosis of AD facilitates the investigation of strategies to reduce the risk for AD progression in the earliest stages of the disease. Pharmacological attempts at curing, halting or modifying it have, by and large, been unsuccessful, and no breakthrough is seen in the near future. However, a lot of elements that seem to contribute to the disease such as risk factors have been identified, mainly from epidemiological and basic research studies. Many of these are amenable to lifestyle modification. Therefore, prevention in the preclinical stage is likely the most effective way to decrease the incidence of this age-associated dreadful neurodegenerative condition, and its associated burden for individuals and society. We provide an overview of modifiable risk factors for AD along with the supporting evidence.
Alzheimer Disease/epidemiology/*prevention & control ; Cognitive Therapy ; Dietary Supplements ; Health Behavior ; Humans ; Mind-Body Therapies ; Motor Activity ; Risk Factors

OBJECTIVETo observe effects of acupuncture and moxibustion on ultrastructure and silent information regulator 1 (SIR1) in hippocampal neuron mitochondria in rats with Alzheimer's disease (AD) in order to explore its possible effective mechanism during the process of protecting mitochondria.

METHODSEighty Wistar rats were randomly divided into a normal group, a sham operation group, a model group and an acupuncture group, 20 rats in each one. The AD model was established in the model group and acupuncture group with injection of Amyloid beta Protein Fragment1-14 (Abeta1-42) into the hippocampus. Acupuncture and moxibustion was applied at "Baihui" (GV 20) and "Shenshu" (BL 23) in the acupuncture group, once a day, seven days as a treatment course and totally two course were required. The rest groups were all fed with normal diet, without any treatment. The transmission electron microscopy, immunohistochemistry and immunoblotting technique were respectively adapted to measure ultrastructure and level of STR1 in hippocampal neuron mitochondria in AD rats.

RESULTSCompared with the model group, the ultrastructure in hippocampal neuron mitochondria in the acupuncture group was effectively improved. The average optical density of SIR1 in hippocampus was 0.21 +/- 0.10 and the gray value was 136.82 +/- 47.42 in the model group, which were obviously lower than 0.47 +/- 0.09 and 281.44 +/- 57.98 in the normal group (both P < 0.01). However, levels of SIR1 in the acupuncture group, they were 0.32 +/- 0.11 and 199.52 +/- 58.12, which were significantly increased compared with those in the model group (both P < 0.05).

CONCLUSIONThe reinforcing-kidney and regulating-Governor Vessel method of acupuncture and moxibustion for AD could improve ultrastructure of mitochondria and increase levels of SIR1 to achieve the aim of recovering injury of mitochondria and protecting function of mitochondria.

Acupuncture Therapy ; Alzheimer Disease ; metabolism ; prevention & control ; therapy ; Amyloid beta-Peptides ; metabolism ; Animals ; Hippocampus ; cytology ; metabolism ; Humans ; Male ; Mitochondria ; metabolism ; Moxibustion ; Neurons ; cytology ; metabolism ; Rats ; Rats, Wistar

Many studies have shown that chronic inflammation occurs in the brain of patients with Alzheimer's disease (AD). It is well known that long-term administration of non-steroidal anti-inflammatory drugs (NSAIDs) can alleviate the cognitive decline of AD patient and elderly. Several inflammatory cytokines produced in the metabolism of arachidonic acid (AA) are closely related to inflammatory diseases. Lipoxygenases (LOXs) and cyclooxygenases (COXs) play a crucial role in the AA network, the products eicosanoids have an important impact on the progression of AD. Although there are many arguments and conflicting evidence, currently LOXs and COXs are still the hot topics in the research on AD pathogenesis and drug development. Here, we review the progress in research on COXs and LOXs, including their actions on CNS and their association with AD, and explore the feasibility of LOXs and COXs as targets for the drugs to prevent and/or treat AD.
Alzheimer Disease ; drug therapy ; enzymology ; prevention & control ; Amyloid beta-Peptides ; metabolism ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; therapeutic use ; Arachidonic Acid ; metabolism ; Brain ; metabolism ; Cyclooxygenase 1 ; metabolism ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase Inhibitors ; therapeutic use ; Humans ; Lipoxygenase Inhibitors ; therapeutic use ; Lipoxygenases ; metabolism ; Prostaglandin H2 ; metabolism ; Prostaglandin-Endoperoxide Synthases ; metabolism

Periodontal disease is a predictor of stroke and cognitive impairment. The association between the number of lost teeth (an indicator of periodontal disease) and silent infarcts and cerebral white matter changes on brain CT was investigated in community-dwelling adults without dementia or stroke. Dental examination and CT were performed in 438 stroke- and dementia-free subjects older than 50 yr (mean age, 63 +/- 7.9 yr), who were recruited for an early health check-up program as part of the Prevention of Stroke and Dementia (PRESENT) project between 2009 and 2010. In unadjusted analyses, the odds ratio (OR) for silent cerebral infarcts and cerebral white matter changes for subjects with 6-10 and > 10 lost teeth was 2.3 (95% CI, 1.38-4.39; P = 0.006) and 4.2 (95% CI, 1.57-5.64; P < 0.001), respectively, as compared to subjects with 0-5 lost teeth. After adjustment for age, education, hypertension, diabetes mellitus, hyperlipidemia, and smoking, the ORs were 1.7 (95% CI, 1.08-3.69; P = 0.12) and 3.9 (95% CI, 1.27-5.02; P < 0.001), respectively. These findings suggest that severe tooth loss may be a predictor of silent cerebral infarcts and cerebral white matter changes in community-dwelling, stroke- and dementia-free adults.
Age Factors ; Aged ; Alzheimer Disease/diagnosis ; Brain/*radiography ; Cross-Sectional Studies ; Dementia/pathology/prevention & control ; Diabetes Complications/diagnosis ; Female ; Humans ; Hyperlipidemias/complications ; Hypertension/complications ; Interviews as Topic ; Male ; Middle Aged ; Odds Ratio ; Periodontal Diseases/complications/*diagnosis ; Predictive Value of Tests ; Risk Factors ; Stroke/pathology/prevention & control ; Tomography, X-Ray Computed ; Tooth Loss

Alzheimer Disease ; drug therapy ; genetics ; prevention & control ; Amyloid beta-Peptides ; genetics ; Animals ; Disease Models, Animal ; Mice ; Mice, Transgenic ; Phytotherapy ; Presenilin-1 ; genetics