Project 1 aims to characterize the accumulation of fibrillar cerebral amyloid-beta (AP) over the age range from the time of onset of Ap deposits to the time when Ap levels approximate those of symptomatic Alzheimer's disease (AD). Project 1 proposes a longitudinal [^^C] PIB imaging study in the cohort of the Adult Children Study (ACS). PET PIB scans will be done on ail ACS participants every two years. The data to be obtained will greatly expand knowledge about preclinical AD and the clinical correlates of Ap accumulation. The long term objective of this effort is to obtain data that will facilitate and foster the design and conduct of clinical trials of anti-Ap therapies for the primary prevention of symptomatic AD. In particular, it aims to help determine the optimal time for intervention in such a trial.
Specific Aims are: 1. Obtain longitudinal [""""""""C] PIB PET scans every 2 years in cognitively normal ACS participants to identify the conversion rate from no or minimal fibrillar Ajj deposition to appreciable AP accumulation, defined by mean cortical binding potential (MCBP) for PIB >0.18, and determine whether this rate is affected by age, APOE genotype, and parental history of AD. 2. Determine the rate and trajectory of change in Ap accumulation in ACS participants, both those with appreciable Ap deposits at their baseline [^^C] PIB PET scan and those lacking Ap deposits at baseline. 3. Examine associations and interactions of cognitive and brain reserve variables (e.g., normalized whole brain volume;regional atrophy;occupation;educational attainment) with longitudinal cognitive performance, obtained in the Clinical Core, in participants with and without Ap accumulation. 4. Correlate findings from Project 1 with appropriate data from Projects 2, 3, and 4 and utilize the Administration (e.g., budgetary oversight), Clinical (e.g., source of participants;longitudinal clinical and cognitive data), Biomarker (e.g., cerebrospinal fluid levels of AP42 in Project 1 participants imaged for Ap deposits), and Data Management and Biostatistics (e.g., data analyses) Cores of this program project grant.

Public Health Relevance

Clarifying the exact timing of amyloid plaque deposition and accumulation that precede symptomatic AD would be extremely helpful in fully understanding the biological origins of AD and to assist in the design of appropriate preventative treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG026276-09
Application #
8732594
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
9
Fiscal Year
2014
Total Cost
$562,356
Indirect Cost
$192,385
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Lucey, Brendan P; Hicks, Terry J; McLeland, Jennifer S et al. (2018) Effect of sleep on overnight cerebrospinal fluid amyloid ? kinetics. Ann Neurol 83:197-204
Jansen, Willemijn J; Ossenkoppele, Rik; Tijms, Betty M et al. (2018) Association of Cerebral Amyloid-? Aggregation With Cognitive Functioning in Persons Without Dementia. JAMA Psychiatry 75:84-95
Gyurkovics, Mate; Balota, David A; Jackson, Jonathan D (2018) Mind-wandering in healthy aging and early stage Alzheimer's disease. Neuropsychology 32:89-101
Islam, Jyoti; Zhang, Yanqing (2018) Brain MRI analysis for Alzheimer's disease diagnosis using an ensemble system of deep convolutional neural networks. Brain Inform 5:2
Roe, Catherine M; Ances, Beau M; Head, Denise et al. (2018) Incident cognitive impairment: longitudinal changes in molecular, structural and cognitive biomarkers. Brain 141:3233-3248
Ihara, Ryoko; Vincent, Benjamin D; Baxter, Michael R et al. (2018) Relative neuron loss in hippocampal sclerosis of aging and Alzheimer's disease. Ann Neurol 84:741-753
Sutphen, Courtney L; McCue, Lena; Herries, Elizabeth M et al. (2018) Longitudinal decreases in multiple cerebrospinal fluid biomarkers of neuronal injury in symptomatic late onset Alzheimer's disease. Alzheimers Dement 14:869-879
Xiong, Chengjie; Luo, Jingqin; Chen, Ling et al. (2018) Estimating diagnostic accuracy for clustered ordinal diagnostic groups in the three-class case-Application to the early diagnosis of Alzheimer disease. Stat Methods Med Res 27:701-714
Gabel, Matthew; Gooblar, Jonathan; Roe, Catherine M et al. (2018) Political Ideology, Confidence in Science, and Participation in Alzheimer Disease Research Studies. Alzheimer Dis Assoc Disord 32:179-184
Roe, Catherine M; Babulal, Ganesh M; Mishra, Shruti et al. (2018) Tau and Amyloid Positron Emission Tomography Imaging Predict Driving Performance Among Older Adults with and without Preclinical Alzheimer's Disease. J Alzheimers Dis 61:509-513

Showing the most recent 10 out of 352 publications