Alzheimer’s disease strategies for disease modification .pdf

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1、REVIEWSAlzheimer’sdisease:strategiesfordiseasemodificationMartinCitronAbstract

2、Alzheimer’sdiseaseisthelargestunmetmedicalneedinneurology.Currentdrugsimprovesymptoms,butdonothaveprofounddisease-modifyingeffects.However,inrecentyears,severalapproachesaimedatinhibitingdiseaseprogressionhaveadvanced

3、toclinicaltrials.Amongthese,strategiestargetingtheproductionandclearanceoftheamyloid-βpeptide—acardinalfeatureofAlzheimer’sdiseasethatisthoughttobeimportantindiseasepathogenesis—arethemostadvanced.Approachesaimedatmodulatingtheabnormalaggregationoftaufilaments(anotherkeyfeatureofthedisease),andt

4、hosetargetingmetabolicdysfunction,arealsobeingevaluatedintheclinic.Thisarticlediscussesrecentprogresswitheachofthesestrategies,withafocusonanti-amyloidstrategies,highlightingthelessonslearnedandthechallengesthatremain.Alzheimer’sdisease(AD)—themostcommonformofclinicalprogrammesarementionedinthec

5、ontextofeachirreversibledementia—isplacingaconsiderableandmechanisticapproach,andinclusionoromissionfromincreasingburdenonpatients,caregiversandsociety,asthisReviewshouldnotbeconstruedasendorsementormorepeoplelivelongenoughtobecomeaffected(BOX1).rejectionofaspecificprogramme.ADisclinicallycharac

6、terizedbyaprogressionfromepisodicmemoryproblemstoaslowglobaldeclineofRationalefordisease-modifyingstrategiescognitivefunctionthatleavespatientswithend-stageDisease-modifyingstrategiescurrentlybeingpursuedforADbedriddenanddependentoncustodialcare,withADarebasedonatleastonelineofevidencethatsup-de

7、athoccurringonaverage9yearsafterdiagnosis1.portsthenotionthatthetargetedprocessisimportantinThecurrentstandardofcareformildtomoderateAD,whichcanbegroupedintothefollowingcategories:ADincludestreatmentwithacetylcholinesterasepathology,geneticsandepidemiology.inhibitorstoimprovecognitivefunction.Th

8、eNMDA(N-methyl-d-aspartate)antagonistmemantinehasalsoPathology.Post-mortemanalysisofhumanADbrainsbeenshowntoimprovecognitivefunctioninpatientsprovidedthefirstcluestothemechanismsofdiseaseandwithmoderatetosevereAD.Inaddition,