We hypothesize that Alzheimer's disease (AD) has a preclinical stage in which elevated levels of brain amyloid protein and accumulation of beta-amyloid deposits foreshadow the gradual onset of neuronal dysfunction, cell loss and dementia. While the exact role of amyloid in the initiation of brain damage is still unclear, clarifying the exact timing of amyloid deposition that precede AD would be extremely helpful in understanding the biological origins of AD and in designing appropriate interventions. Brain imaging provides a window into many of the hypothesized biochemical, functional and anatomic changes in AD. With Positron Emission Tomography (PET) using [11C]PIB it is possible to estimate the density of beta-amyloid plaques by imaging the PIB binding sites. With PET using [18F]FDG it is possible to estimate neuronal function from measures of metabolic activity. Finally, with magnetic resonance imaging (MRI) volume loss over time can be quantified in regional and global brain measures. It is our premise that by examining the temporal and spatial interrelationships between these three measures important insights will be gained in the pathophysiology of AD. The value of these imaging biomarkers are further enhanced by combining the data with CSF biomarkers and clinical and psychometric data. Towards these goals, the Imaging Core will provide two key support activities to the DIAN effort:
Aim 1 : Oversee the collection of all image data. This data includes MR scans for morphometrics, PET FDG scans for metabolism and PET PIB scans for imaging beta-amyloid plaques.
Aim 2 : Perform image processing and analysis to extract biologically relevant measures from the image data set. These measures include whole brain volume and cortical and subcortical regional measures of gray matter volume, relative glucose metabolism and PIB-derived estimates of beta-amyloid plaque deposition.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AG032438-05
Application #
8425006
Study Section
Special Emphasis Panel (ZAG1-ZIJ-1)
Project Start
2013-01-01
Project End
2014-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
5
Fiscal Year
2013
Total Cost
$740,648
Indirect Cost
$55,662
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Su, Yi; Blazey, Tyler M; Snyder, Abraham Z et al. (2015) Partial volume correction in quantitative amyloid imaging. Neuroimage 107:55-64
Fagan, Anne M; Xiong, Chengjie; Jasielec, Mateusz S et al. (2014) Longitudinal change in CSF biomarkers in autosomal-dominant Alzheimer's disease. Sci Transl Med 6:226ra30
Xiong, Chengjie; Luo, Jingqin; Gao, Feng et al. (2014) Optimizing parameters in clinical trials with a randomized start or withdrawal design. Comput Stat Data Anal 69:101-113
Brier, Matthew R; Thomas, Jewell B; Snyder, Abraham Z et al. (2014) Unrecognized preclinical Alzheimer disease confounds rs-fcMRI studies of normal aging. Neurology 83:1613-9
Xiong, Chengjie; Weng, Hua; Bennett, David A et al. (2014) Subsets of a large cognitive battery better power clinical trials on early stage Alzheimer's disease. Neuroepidemiology 43:131-9
Storandt, Martha; Balota, David A; Aschenbrenner, Andrew J et al. (2014) Clinical and psychological characteristics of the initial cohort of the Dominantly Inherited Alzheimer Network (DIAN). Neuropsychology 28:19-29
Ting, Simon Kang Seng; Benzinger, Tammie; Kepe, Vladimir et al. (2014) A novel PSEN1 mutation (I238M) associated with early-onset Alzheimer's disease in an African-American woman. J Alzheimers Dis 40:271-5
Gordon, Brian A; Blazey, Tyler; Benzinger, Tammie Ls (2014) Regional variability in Alzheimer's disease biomarkers. Future Neurol 9:131-134
Ryman, Davis C; Acosta-Baena, Natalia; Aisen, Paul S et al. (2014) Symptom onset in autosomal dominant Alzheimer disease: a systematic review and meta-analysis. Neurology 83:253-60
Dobrowolska, Justyna A; Kasten, Tom; Huang, Yafei et al. (2014) Diurnal patterns of soluble amyloid precursor protein metabolites in the human central nervous system. PLoS One 9:e89998

Showing the most recent 10 out of 20 publications