Calculating the Number of People with Alzheimers Disease in any Country Using Saturated Mutation Models of Brain Cell Loss that also Predict Widespread Natural Immunity to the Disease英文文献资料.docVIP

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Calculating the Number of People with Alzheimers Disease in any Country Using Saturated Mutation Models of Brain Cell Loss that also Predict Widespread Natural Immunity to the Disease英文文献资料.doc

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Calculating the Number of People with Alzheimers Disease in any Country Using Saturated Mutation Models of Brain Cell Loss that also Predict Widespread Natural Immunity to the Disease英文文献资料

ComputationalandMathematicalMethodsinMedicine Vol.11,No.2,June2010,119–159 CalculatingthenumberofpeoplewithAlzheimer’sdiseaseinany countryusingsaturatedmutationmodelsofbraincelllossthatalso predictwidespreadnaturalimmunitytothedisease IvanKramer* DepartmentofPhysics,UniversityofMarylandBaltimoreCounty,1000HilltopCircle,Catonsville, MD21250,USA (Received3May2007;?nalversionreceived16March2009) The series of mutations that cause brain cells to spontaneously and randomly die leadingtoAlzheimer’sdisease(AD)ismodelled.TheprevalenceofADasafunction ofageinmalesandfemalesiscalculatedfromtwoverydifferentmutationmodelsof braincelldeath.Oncetheprevalencefunctionsaredetermined,thenumberofpeople withADinanycountryorcitycanbeestimated. Themodelsdevelopedheredependonthreeindependentparameters:thenumberof mutations necessary for a brain cell associated with AD to spontaneously die, the averagetimebetweenmutations,andthefractionoftheriskpopulationthatisimmune todevelopingthedisease,ifany.Thevaluesoftheseparametersaredeterminedby ?ttingthemodel’sADincidencefunctiontotheincidencedata. Thebest?tstotheincidenceratedatapredictthatasmuchas74.1%ofmalesand 79.5%offemalesmaybenaturallyimmunetodevelopingAD.Thus,thedevelopment ofADisnotanormalorinevitableresultoftheagingprocess.These?tsalsopredict thatmalesandfemalesdevelopADthroughdifferentpathways,requiringadifferent numberofmutationstocausethedisease.ThenumberofpeopleintheUSAwithADin theyear2000isestimatedtobe451,000. ItisofparamountimportancetodeterminethenatureoftheimmunitytoADpredicted here.Findingwaysofblockingthemutationsleadingtotherandom,spontaneousdeath ofmemorybraincellswouldpreventADfromdevelopingaltogether. Keywords: Alzheimer’s disease; mutation model; prevalence; incidence rate; brain cellloss 1. Theorderedmutationmodeloflate-onsetAlzheimer’sdisease Alzheimer’sdisease(AD)beginswhenneuronsinthebrainspontaneouslybegindyingin adisorganizedwaytakingsomememorywithit.ResearchdatasuggeststhatADresults fromaseriesofrandommissensemutati