Both Alzheimer?s disease (AD) and depression have become increasingly more prevalent in the homebound elderly, leading to increased rates of morbidity, nursing home placement and mortality, than what are found in the general elderly population. Our cross-sectional study of an established homebound population in the Boston area has found that low plasma amyloid-a42 (Aa42) is associated with depression independently of cardiovascular disease. We further found that depression with low Aa42 combined with high Aa42 in plasma is associated with poor memory. Similarly other research studies have shown that a high plasma Aa40/Aa42 ratio significantly increased the risk of AD. Multiple studies demonstrate that plasma Aa correlates with cerebral spinal fluid (CSF) Aa when cognition is normal, but this equilibrium disappears after the AD cognitive symptoms occur. We hypothesize the existence of a potential depression subtype associated with Ab peptides in plasma, which we have termed ?amyloid-associated depression?. The purpose of this R01 application is to validate the existence of amyloid-associated depression defined by a high plasma Aa40/Aa42 ratio, and to investigate whether this depression subtype is a prodromal depression of AD. The proposal is based on our established population, and has two aims:
Aim 1 is to document memory decline prospectively in those with amyloid-associated depression vs. those with non-amyloid depression vs. the controls.
Aim 2 is to investigate the relationship between plasma Aa and CSF Aa, a central nervous system (CNS) biomarker of AD, in the different depression subgroups. Our long-term goal is to identify prodromal signs of AD to help facilitate early treatment of the disease in the homebound elderly population.

Public Health Relevance

The proposed longitudinal study seeks to validate amyloid associated depression by investigating whether the combination of depression and a high plasma Aa40/Aa42 ratio will lead to greater risk of cognitive decline and the finding of the AD biomarkers in CSF as compared to those with a low plasma Aa40/Aa42 ratio or those without depression.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG031171-03
Application #
8096676
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
2011-07-01
Budget End
2012-06-30
Support Year
3
Fiscal Year
2011
Total Cost
$401,529
Indirect Cost
Name
Boston University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
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
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, 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
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

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