Alzheimer s disease AD AD

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1 DOI: /j.cnki.jinn.2013.z1.025 Journal of International Neurology and Neurosurgery 3 Lehti Maki T Dastidar P Jokela H et al. Effect of long term hormone replace -ment therapy on atherosclerosis progression in post menopausal women relates to functional apolipoprotein E genotype. Clin Endocrinol Metab Giassakisi G Veletza S Papanas N et al. Apolipoprotein E and First -ever Ischaemic Stroke in Greek Hospitalized Pa- 4. ApoE tients. J Int Med Res Kokubo Y Chowdhury AH Date C et al. Age -dependent 5. association of apolipoprotein E genotype with stroke subtypes in a Japanese rural population. Stroke Paternoster L Martínez González NA Lewis S et al. Association Between Apolipoprotein E Genotype and Carotid Intima - Media Thickness May Suggest a Specific Effect on Large Artery Atherothrombotic Stroke. Stroke Szolnoki Z Somogyvari F Kondacs A et al. Evaluation of the interactions of common genetic mutations in stroke subtypes. J Neurol Schilling S Destfano AL Sachdev PS et al. APOE genotype and MRI markers of cerebrovascular disease Systematic review and meta -analysis. Neurology Chiou LL Ching KL Ruey TL et al. Association Of Apolipoprotein E Polymorphism With Ischemic Stroke Subtypes In TAIWAN. Kaohsiung J Med Sci Biffi A Sonni A Anderson CD et al. Variants at APOE influence risk of deep and lobar intracerebral hemorrhage. Ann Neurol Pezzini A Padovani A. Cerebral amyloid angiopathy -related hemorrhages. J Neurol Sci Sullivan PM Mace BE Estrada JC et al. Human apolipoprotein E4 targeted replacement mice show increased preva- 8. E lence of intracerebral hemorrhage associated with vascular amyloid deposition Stroke Cerebrovasu Dis Tzourio C Arima H Harrap S et al. etheicity and the risk of cerebral hemorrhage ApoE genotype Neurology Biffi A Soaai A Anderson CD et al. Variants at APOE iffluence 1 0. E risk of deep and lobar intracerebral hemorrhage. Neurol Ann 1 1 Tascilar N Dursun A Ankarali H et al. Relationship of 2 0 Biffi A Christopher D Anderson MD et al. APOE Genotype apoe polymorphism with lipoprotein a apoa apob and lipid levels in atherosclerotic infarct. J Neurolog Sci Predicts Extent of Bleeding and Outcome in Lobar Intracerebral Hemorrhage. Lancet Neurol MicroRNA mirna mirna MicroRNA MicroRNA Alzheimer s disease AD AD

2 senile plaque SP neurofibrillary tangles NFTs SP amyloid precursor protein APP β 1 beta amyloid cleaving 2007 Lukiw 2 enzyme 1 BACE1 γ AD mirnas Lukiw β amyloid β -protein Aβ NFTs mirna Tau 1 AD mirna mirna 21 ~ 23 RNA mrna 3 untranslated regions UTR AD mirna AD mrna mirna 5 AD mirna 2 ~ 8 mirna mir -29 mir -15 mir -107 mir -181 mir -146 mrna seed region mirna APP BACE1 MAPT microtubule -associated mir -9 mir -101 mir -106 mirna protein tau AD DNA AD mirna mirna 1 1 AD mirna 1 microrna AD microrna AD AD mir-181 ATM DNA mir-146 DNA / RANTES IRAK1 mir-101 APP APP APP Aβ COX2 MAGL2 Tau Tau mir-15 Bcl-2 ERK1 Tau Tau mir-29 BIM BMF HRK Puma BACE1 Aβ Aβ mir-107 BACE1 Aβ Aβ Dicer mirna mirna cofilin CDK6 mir-106 Rb1 p21 APP P73 APP APP Aβ Tau /Tau P62 Aβ 2 AD mirna 2. 1 mir -181 mir mir -181 a mir - mir -181 a mir -181 b 42 β mir -181 c mirna 4 mir -181 c 181 b mir -181 c mir -181 d DNA mir -181 c AD ataxia telangiectasia mutated ATM DNA mir -181 d AD

3 Journal of International Neurology and Neurosurgery AD DNA 2. 4 mir -29 mir -181 c mir mir -29 a mir -29 b DNA mir -29 c 2. 2 mir -146 mir - mir -146 mir -146 a mir -146 b AD mir -146 a Bim Bmf Hrk Puma Bcl -2 mir -146 b C 6 mir -146 a mir -29 b Bcl -2 mir -146 b AD IL -1 C AD NF -κb mir a 7 AD mir -29 b NF -κb 8 mir - BACE1 146 a mir -146 b β mir -146 a AD mir -146 a RANTES I- RAK1 6 mir -146 a mir -29 b 29 c BACE1 AD Aβ AD mir -15 mir -146 mir-15 mir-15 a mir-15 b mir-16 AD mir-195 mir-424 mir-497 mir-503 mir mir -101 APP mir UTR mir -101 AD 16 AD tau mir -101 mir -101 APP AD APP 1 ERK1 mir -101 Aβ 10 mir -15 ERK1 mir -101 COX -2 ERK1 / 2 AD mir -15 a NFTs mirna 11 mir -101 APP tau 17 COX -2 Tau AD AD mir -101 mir -15 tau MGI2 MGI2 tau AD tau 2. 6 mir -107 tau NFTs AD mir -107 mir -107 / 103 mir -107 / 12 mir mir -15 APP COX -2 Tau AD b mir -29 b mir -29 b mir -29 c BACE1 3 UTR β mir -29 mir -15 Bcl -2 tau mir mir -15

4 Lukiw WJ. Micro -RNA speciation in fetal adult and Alzhei- mir -107 AD MCI mer s disease hippocampus. Neuroreport BACE1 mrna Geekiyanage H Chan C. MicroRNA / c regulates mir -107 serine palmitoyltransferase and in turn amyloid β novel targets in sporadic Alzheimer s disease. J Neurosci AD β 20miR -107 AD Schonrock N Ke YD Humphreys D et al. Neuronal microrna deregulation in response to Alzheimer s disease amy- AD 2. 7 mir -106 loid -beta. PLoS One e mir -106 mir Wang Y Yu Y Tsuyada A et al. Transforming growth factor -β regulates the sphere -initiating stem cell -like feature in mir -17 mir -18 mir -20 mir -93 mir -106 mir -106 a mir -106 b 21 breast cancer through mirna and ATM. Oncogene mir -106 a APP 3 UTR APP mir -106 a APP mir -106 a mir106 b 6 Cui JG Li YY Zhao Y et al. Differential regulation of interleukin -1 receptor -associated kinase -1 IRAK -1 and I- RAK -2 by microrna a and NF -kappab in stressed hu- APP mir -106 b man astroglial cells and in Alzheimer disease. J Biol Chem APP AD 22 mir b 1 retinoblastoma protein 1 p21 22 mary human brain cells. Exp Neurol Lukiw WJ. NF -кb -regulated micro RNAs mirnas in pri- 21 p73 p73 tau AD p Vilardo E Barbato C Ciotti M et al. MicroRNA regulates tau p73 amyloid precursor protein expression in hippocampal neurons. J Biol Chem tau mir -106 a 1 1 Yokota O Terada S Ishizu H et al. Cyclooxygenase -2 in mir106 b AD Aβ the hippocampus is up -regulated in Alzheimer s disease but not in variant Alzheimer s disease with cotton wool plaques 3 in humans. Neurosci Lett mirna AD 1 2 Sachdeva M Wu H Ru P et al. MicroRNA mediated AD mirna AD mirna Akt activation and estrogen -independent growth. gene Onco- 1 3 Kole AJ Swahari V Hammond SM et al. mir -2 9 b is activated during neuronal maturation and targets BH3 -only genes RNA mirna AD to restrict apoptosis. Genes Dev Lewis BP Burge CB Bartel DP. Conserved seed pairing often flanked by adenosines indicates that thousands of human genes are microrna targets. Cell AD mir -106 b 8 Granic I Dolga AM Nijholt IM et al. Inflammation and NF -kappab in Alzheimer s disease and diabetes. J Alzheimers Dis mir -106 b p73 9 Lee YJ Han SB Nam SY et al. Inflammation and Alzheimer s disease. Arch Pharm Res Hébert SS Horré K Nicola L et al. Loss of microrna cluster mir -2 9 a / b -1 in sporadic Alzheimer s disease correlates with increased BACE1 / beta -secretase expression. Proc Natl Acad Sci U S A Zong Y Wang H Dong W et al. mir -2 9 c regulates BACE 1 protein expression. Brain Res

5 Journal of International Neurology and Neurosurgery 1 6 Cimmino A Calin GA Fabbri M et al. mir -1 5 and mir induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A Hébert SS Papadopoulou AS Smith P et al. Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration. Hum Mol Genet Finnerty JR Wang WX Hébert SS et al. The mir -1 5 / group of microrna genes evolutionary biology cellular functions and roles in human diseases. J Mol Biol Nelson PT Wang WX. MiR is reduced in Alzheimer s disease brain neocortex validation study. J Alzheimers Dis Bonda DJ Lee HP Kudo W et al. Pathological implications of cell cycle re -entry in Alzheimer disease. Expert Rev Mol Med e Hébert SS Horré K Nicola L et al. MicroRNA regulation of Alzheimer s Amyloid precursor protein expression. Neurobiol Dis Wang PY Li YJ Zhang S et al. Regulating A5 4 9 cells growth by ASO inhibiting mirna expression. Mol Cell Biochem Kim YK Yu J Han TS et al. Functional links between clustered micrornas suppression of cell -cycle inhibitors by microrna clusters in gastric cancer. Nucleic Acids Res Patel N Hoang D Miller N et al. MicroRNAs can regulate human APP levels. Mol Neurodegener Sampath D Calin GA Puduvalli VK et al. Specific activation of microrna1 0 6 b enables the p7 3 apoptotic response in chronic lymphocytic leukemia by targeting the ubiquitin ligase Itch for degradation. Blood Meenhuis A van Veelen PA de Looper H et al. MiR / 2 0 / 9 3 / promote hematopoietic cell expansion by targeting sequestosome 1 -regulated pathways in mice. Blood β β Aβ β β normal brain aging β beta amyloid Aβ AD NBA Alzheimer s disease AD 1 mild cognitive impairment MCI 4 Aβ Aβ deposition Aβ lixingqiangsyy@ yeah. net ypengcao@ yahoo. com 466

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