In this application, we propose to characterize a novel blood biomarker of Alzheimer's disease (AD). We previously demonstrated in a pilot study that the dynamic changes in plasma amyloid-beta (A?) levels after administration of an OGTT (hitherto referred to as ?A?-OGTT??) differentiates mild cognitive impairment (MCI) subjects from clinically normal (CN) subjects. In this proposal, we will demonstrate the following: (i) A?-OGTT? can also differentiate AD subjects from CN subjects; (ii) A?-OGTT? is associated with brain A? burden on Pittsburg Compound B-Positron Emission Tomography (PiB-PET); (iii) the mechanism of A?-OGTT? may be due to the role of A?-binding proteins (chaperones). In a cross-sectional study, we will administer OGTT to a group of individuals in each of the MCI, AD and CN groups. Plasma samples will be obtained at various time points after the administration of OGTT. Plasma samples will be quantified for A? 40, 42, and A? binding proteins. A?-OGTT? value will be calculated for all groups to determine if there are differences among the three groups. A?-OGTT? value will also be correlated with A? burden on PiB-PET in CN to determine if the plasma biomarker is reflective of the underlying pathology in a preclinical population. Finally, A?-OGTT? value will be correlated with A? binding protein levels. The results of this proposal will provide data regarding the potential utility of A?-OGTT? as a diagnostic biomarker of MCI and AD, as well as a biomarker of underlying disease state. It will also provide data on the potential relationship between plasma A? 40 and 42 levels and A? binding proteins, and whether there may be a more efficient clearance of A? in NC. In addition, the data from this proposal will enable us to gather sufficient data to design a longitudinal study to demonstrate the utility of A?-OGTT? in differentiating subjects, predict disease progression, and monitor therapeutic response.

Public Health Relevance

The goal of the proposed project is to develop a simple, non-invasive and easily accessible blood biomarker for Alzheimer's disease (AD). We will use oral glucose tolerance test (OGTT), which is already available in most community laboratories, to determine if the changes in the blood amyloid level after an OGTT can be helpful as a marker for AD. We will also determine if the changes in blood amyloid is reflective of the brain amyloid load, and to determine if we can understand how amyloid may be cleared from the blood.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG057725-04
Application #
9936131
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Luo, Yuan
Project Start
2017-09-15
Project End
2021-05-31
Budget Start
2020-06-15
Budget End
2021-05-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Kim, Yejin; Rosenberg, Paul; Oh, Esther (2018) A Review of Diagnostic Impact of Amyloid Positron Emission Tomography Imaging in Clinical Practice. Dement Geriatr Cogn Disord 46:154-167