Amyloid-beta Peptides, Depression and Alzheimer's Disease

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BothAlzheimer'sdisease(AD)anddepressionhavebecomeincreasinglymoreprevalentin thehomeboundelderly,leadingtoincreasedratesofmorbidity,nursinghomeplacementand mortality,thanwhatarefoundinthegeneralelderlypopulation.Ourcross!sectionalstudyofan establishedhomeboundpopulationintheBostonareahasfoundthatlowplasmaamyloid!b42 (Ab42)isassociatedwithdepressionindependentlyofcardiovasculardisease.Wefurther foundthatdepressionwithlowAb42combinedwithhighAb40inplasmaisassociatedwith poormemory.SimilarlyotherresearchstudieshaveshownthatahighplasmaA¿40/A¿42 ratiosignificantlyincreasedtheriskofAD.MultiplestudiesdemonstratethatplasmaA¿ correlateswithcerebralspinalfluid(CSF)A¿whencognitionisnormal,butthisequilibrium disappearsaftertheADcognitivesymptomsoccur.Wehypothesizetheexistenceofa potentialdepressionsubtypeassociatedwithAbpeptidesinplasma,whichwehavetermed "amyloid!associateddepression".ThepurposeofthisR01applicationistovalidatethe existenceofamyloid!associateddepressiondefinedbyahighplasmaA¿40/A¿42ratio,andto investigatewhetherthisdepressionsubtypeisaprodromaldepressionofAD.Theproposalis basedonourestablishedpopulation,andhastwoaims:Aim1istodocumentmemorydecline prospectivelyinthosewithamyloid!associateddepressionvs.thosewithnon!amyloid depressionvs.thecontrols.Aim2istoinvestigatetherelationshipbetweenplasmaA¿and CSFA¿,acentralnervoussystem(CNS)biomarkerofAD,inthedifferentdepression subgroups.Ourlong!termgoalistoidentifyprodromalsignsofADtohelpfacilitateearly treatmentofthediseaseinthehomeboundelderlypopulation.