The proposed research """"""""Aging in prosimian primate: model for AD pathology"""""""" is based on the finding that several possibly related syndromes occur during CNS aging in the prosimian primate species of Otolemur. These include: central cholinergic dystrophy, beta-amyloidosis (plaques and vascular amyloid), and central acute phase response (activated microglia and elevated interleukin-1 levels). In addition, these animals manifest spontaneously in captivity dietary iron overload syndrome and mild copper deficiency which may be associated with CNS aging pathology.
The specific aims are:
SPECIFIC AIM 1 : To test a series of Otolemurs of various ages for the attributes of copper deficiency in peripheral tissues and CNS, and to correlate iron and copper status with abnormalities in acute phase proteins (ceruloplasmin and beta-amyloid protein), abnormality in central noradrenergic and cholinergic pathways, appearance of beta-amyloidosis (vascular and plaque), and abnormalities in central immune mechanisms (gliosis, interleukin levels, and activation of microglia).
SPECIFIC AIM 2 : To test whether all prosimians with DIOS have 'chronic' acute phase response and the relationship to copper deficiency; and to see whether chronic stimulation of acute phase response produces a stepwise increase in CNS injury.
SPECIFIC AIM 3 : To test the longterm effect of altering trace mineral balance, and of protective drug regimens to CNS injury in cohorts of young Otolemur and other prosimians followed for 4-5 years to the age where CNS injury is evident in 'normal' captive Otolemur. The goal of the proposed research is to describe the relationship between peripheral abnormalities and central nervous system aging in Otolemur. Understanding the temporal sequence and cellular basis of these aging changes may further rational prevention and treatment. Vulnerability to age-related CNS injury in Otolemur may be pertinent to mechanisms n human aging and diseases with AD pathology.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
5P50AG005128-08
Application #
3802473
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Duke University
Department
Type
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Petyuk, Vladislav A; Chang, Rui; Ramirez-Restrepo, Manuel et al. (2018) The human brainome: network analysis identifies HSPA2 as a novel Alzheimer’s disease target. Brain 141:2721-2739
Sims, Rebecca (see original citation for additional authors) (2017) Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. Nat Genet 49:1373-1384
Jun, Gyungah R; Chung, Jaeyoon; Mez, Jesse et al. (2017) Transethnic genome-wide scan identifies novel Alzheimer's disease loci. Alzheimers Dement 13:727-738
Karch, Celeste M; Ezerskiy, Lubov A; Bertelsen, Sarah et al. (2016) Alzheimer's Disease Risk Polymorphisms Regulate Gene Expression in the ZCWPW1 and the CELF1 Loci. PLoS One 11:e0148717
Mez, Jesse; Mukherjee, Shubhabrata; Thornton, Timothy et al. (2016) The executive prominent/memory prominent spectrum in Alzheimer's disease is highly heritable. Neurobiol Aging 41:115-121
Ridge, Perry G; Hoyt, Kaitlyn B; Boehme, Kevin et al. (2016) Assessment of the genetic variance of late-onset Alzheimer's disease. Neurobiol Aging 41:200.e13-200.e20
Hohman, Timothy J; Bush, William S; Jiang, Lan et al. (2016) Discovery of gene-gene interactions across multiple independent data sets of late onset Alzheimer disease from the Alzheimer Disease Genetics Consortium. Neurobiol Aging 38:141-150
Jun, G; Ibrahim-Verbaas, C A; Vronskaya, M et al. (2016) A novel Alzheimer disease locus located near the gene encoding tau protein. Mol Psychiatry 21:108-17
Hohman, Timothy J; Cooke-Bailey, Jessica N; Reitz, Christiane et al. (2016) Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk. Alzheimers Dement 12:233-43
Ghani, Mahdi; Reitz, Christiane; Cheng, Rong et al. (2015) Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals. JAMA Neurol 72:1313-23

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