Abstract

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:
Aim1 istodocumentmemorydecline prospectivelyinthosewithamyloid!associateddepressionvs.thosewithnon!amyloid depressionvs.thecontrols.
Aim2 istoinvestigatetherelationshipbetweenplasmaA?and CSFA?,acentralnervoussystem(CNS)biomarkerofAD,inthedifferentdepression subgroups.Ourlong!termgoalistoidentifyprodromalsignsofADtohelpfacilitateearly treatmentofthediseaseinthehomeboundelderlypopulation.

Public Health Relevance

Theproposedlongitudinalstudyseekstovalidateamyloidassociateddepression byinvestigatingwhetherthecombinationofdepressionandahighplasma A?40/A?42ratiowillleadtogreaterriskofcognitivedeclineandthefindingofthe ADbiomarkersinCSFascomparedtothosewithalowplasmaA?40/A?42ratio orthosewithoutdepression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG031171-04
Application #
8284382
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Hsiao, John
Project Start
2009-07-15
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$400,461
Indirect Cost
$147,660

  Institution

Name
Boston University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118

  Publications

Zhu, Andrea Q; Kivork, Christine; Vu, Linh et al. (2017) The association between hope and mortality in homebound elders. Int J Geriatr Psychiatry 32:e150-e156
Zhu, Haihao; Stern, Robert A; Tao, Qiushan et al. (2017) An amylin analog used as a challenge test for Alzheimer's disease. Alzheimers Dement (N Y) 3:33-43
Qiu, Wei Qiao; Himali, Jayandra J; Wolf, Philip A et al. (2017) Effects of white matter integrity and brain volumes on late life depression in the Framingham Heart Study. Int J Geriatr Psychiatry 32:214-221
Zhu, H; Wang, X; Wallack, M et al. (2015) Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer's disease. Mol Psychiatry 20:252-62
Qiu, Wendy Wei Qiao; Lai, Angela; Mon, Timothy et al. (2014) Angiotensin converting enzyme inhibitors and Alzheimer disease in the presence of the apolipoprotein E4 allele. Am J Geriatr Psychiatry 22:177-85
Qiu, Wei Qiao; Wallack, Max; Dean, Michael et al. (2014) Association between amylin and amyloid-? peptides in plasma in the context of apolipoprotein E4 allele. PLoS One 9:e88063
Qiu, Wei Qiao; Mwamburi, Mkaya; Besser, Lilah M et al. (2013) Angiotensin converting enzyme inhibitors and the reduced risk of Alzheimer's disease in the absence of apolipoprotein E4 allele. J Alzheimers Dis 37:421-8
Zhu, Haihao; Bhadelia, Rafeeque A; Liu, Zhiheng et al. (2013) The association between small vessel infarcts and the activities of amyloid-? peptide degrading proteases in apolipoprotein E4 allele carriers. Angiology 64:614-20
Vu, Linh N; Dean, Michael J; Mwamburi, Mkaya et al. (2013) Executive function and mortality in homebound elderly adults. J Am Geriatr Soc 61:2128-34
Liu, Zhiheng; Zhu, Haihao; Fang, Guang Guang et al. (2012) Characterization of insulin degrading enzyme and other amyloid-? degrading proteases in human serum: a role in Alzheimer's disease? J Alzheimers Dis 29:329-40

Showing the most recent 10 out of 17 publications