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Alzheimer’s Disease Genetics Pathogenesis Models and Experimental Therapeutics
?????? ???? ????? ???? ?? gene?? risk factors?? ?? ???? ????? ?? ?? ???. ??? 0.1%? ??? ????????? ??? ?? ?? ??? ?? ?? ???. ?????????????? ?????? ???? ??? ?? ??? ??? ?? ?? ??? ??? ???? ?? APP? presenilins1? 2? APP ? presenilin genes ????? ?? ?? A-beta42? ?? ???? ??? risk factor? ? ??? APOE? ??? ApoE? E2, E3, E4 gene ??? ??? ??, ???? ?? ??? ?? ????? ????? ???? ??? ????? ???? ??? ????? ?? ???. ???? ?????? ?? ???? E4 gene? ???? ??? ?? ? E4 gnee? ?????? ??? ?? ????. ????????: ? ? ?? ??? ???? ??? ??? ??? ???? ??? ?? ?? ???? ?? ???? ????? ??? ??? ApoE4 ?? ???? ??? ???? ?? ???? ??? ? ???? ???? ??? ?? ?????? ??????? ????? ???? ??? ???? ??? ???? ??? ?????????????? ?????? ???? ??? ?? ??? ??? ?? ?? ??? ??? ???? ?? APP? presenilins1? 2? ??? ??? ???? PSEN1? 14? ???? ???? gene?? ? gene? ??? ??? ??????? ???? ?? ???? ? ???? APP(????? ??? ???)? ?? ?? ????? ?? ????? cleavesed? ?????? ??? ??? ??? ??? 1????? ??? PSEN2? PSEN1? ??? ??? ??? ??? ????. ????? APP? ????????????? ???21?? ???? ??? ???? ??? ?????? ???? ???. * ??? Secretase family? ?? BACE1? β-amyloid cleaving enzyme1?? ? transmembrane aspartyl protease? APP? A-beta? site?? APP? cleavage? ??? ?????? ??? ?? ??? ????? ????? γ-secretase? multiprotein catalytic complex? PS1? PS2? ???? type 1 transmembrane glycoprotein? nicastrin? multipass transmembrane protein? Apha1? Pen-2 ? ????. ???? ???? α-Secretase? ?? cleavage ?? ?? APP NTP((APPs-α)? APP CTF(C83)? ?? ??? ??? ?? γ-secretase? ?? ?? ?? ?????? ???? ?? P3?? A-beta?? ?? peptide? APP intracellular domain(AICD)fragment? ?? ?? ??? Aβ domain? ???? ?? amyloidogenesis? ???. ??? ????? ??? ??? APP? β-secretase? ?? ??? ?? APP NTF(APPs-β) APP CTF(C99)? ???? Amyloidogenic pathway? ??? ?? ??? C99 fragment? γ-secretase? ?? ?? Aβ? AICD? ?????. ??? snile plague? ???? ???? ???? ?? ???. APP intracellular domain (AICD):nuclear signaling * ??? ?????? ???? Aβ amyloidosis? taupathy? ??? ?? ?????? A-beta? 39-43 ????? ????? ???? ?? ?????? ?? ???? ??? ??? amyloid plaque? ?? ???. ?
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