2 455 1 230031 R741 A 1005-9202201302-0455-05doi10. 3969 /j. issn. 1005-9202. 2013. 02. 111 6 1 β- 1. 1 EO Aβ SP NP 1. 1. 1 APP APP 21q21. 1-21. 3 NFT APP18 17 65 EO 170 kb 770 APP LO LO 94% 7 1α F S EO α γ F LO S APPsAPPα P3Aβ 17-40 Aβ 17-42 APP α Aβ16 ~ 1 17 Aβ SP 2β β- β γ sappβ AβAβ 40 Aβ 42 APP -1PSEN1-2PSEN2 APP 2 3 LO α β 4 APOE LO 5 Aβ 40 Aβ 42 Aβ APOE LO Aβ LO 1 Aβ LO 8 1 APP 21q21. 1-21. 3 A692G E693G D694N A713T PSEN1 14q24. 3 Phe105Val Pro117Arg His163Arg PS-1 PSEN2 1q31-42 A85V PS-2 APOE 19q13. 2 APOE _ε2 /3 /4 CLU 8p21 rs11136000 MAPT 17q21. 3 rs62063857 tau CR1 1q32 rs3818361 1 SORL1 11q23. 2-q24. 2 rs641120 APP Aβ TOMM40 19q rs10524523 PLAU 10q22. 2 rs2227564 upa Aβ CALHM1 10q24. 33 rs2986017 rs17853566 Ca 2 + 9 APP 39 8 21 APP A692G E693G D694N A713TF CAA 10 11 31 No. 2003z026 12 APP A673V 1 1958-1. 1. 2 PSEN1 PSEN2 PSENl 14q24. 3 1964-13 3 ~ 12 467 24 6 1 PS-1 PSEN2 1q31-42 12 3 ~ 12
456 2013 1 33 448 PS-2 401 182 PSEN1 1. 2. 3 tau MAPT 23 14 PSEN2 http/ /www. molgen. vib-ua. be /Mutations / PSEN2 tau MAPT 2 3 10 taumapt 17q21. 3 100 kb16 26 40 ~ 90 mrna 6 tau 13 PSEN1 N 0 ~ 2 C 3 ~ 4 14 PSEN1 27 NFT NFT 4 Phe105Val 5 PHF tau 28 Pro117Arg Glu120Gly 6 His163Arg 7 tau Leu226Phe 8 Val261Leu Val272Ala Leu282Arg 12 Ile439Ser H1 H2 H2 Kumar 15 20% ~ 30% 29 30 PSEN1 Aβ 42 Aβ 40 Aβ 42 16 Aβ 40 E120G 32 33 PSEN1 5 34 EO 1. 2 LO LO 133 kb TATA CR1 60% ~ 80% 17 Bertram 18 LO AlzGene Aβ C3b 2011 10 695 http/ /www. alzgene. org / CR1 C3b Aβ C3b Aβ 35 1. 2. 1 E ApoEApoE CR1 19 19q13. 2 3. 7 kb4 3 6 ε2 /2 ε3 /3 ε4 /4 ε2 /3 ε2 /4 ε3 /4 ApoEε4 1883 CR1 CR1 CSF ApoEε4 LO CR1 19 ε2 ε3 ApoEε4 ε4 Aβ Aβ CR1 LCR 20 Kim 21 ApoE 2 ~ 3 MAPT H1 31 MAPT 1. 2. 4 1CR1CR1 1q32 38 T rs3818361 P = 0. 014 OR = 1. 15 36 CNV CR1 CR1-F CR1-S CR1-S 30% 37 1. 2. 2 CLU CLU 8p21449 1. 2. 5 sortilin SORL1SORL1 ApoE Aβ Aβ SNP SORL1 SNP S 22 ApoJ CLU SORL1 S 39 ~ 42 SORL1 rs641120 T /C 75 000 ~ 80 000 Clusterin JApoJ SORL1 LR11 11q23. 2-q24. 2 177. 49 kb J SORL1 APP Aβ SORL1 CLU Aβ Aβ Rogaeva 38 CLU 6 SORL1 CLU SNP 5' Rogae- 38 S 23 rs11136000 CLU va 16% 24 Lee 43 25 CLU S SORL1 SNP rs11136000 C 88%
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