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.
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.
|Chen, Ling; Sun, Jianguo; Xiong, Chengjie (2016) A multiple imputation approach to the analysis of clustered interval-censored failure time data with the additive hazards model. Comput Stat Data Anal 103:242-249|
|Staley, Lyndsay A; Ebbert, Mark T W; Parker, Sheradyn et al. (2016) Genome-wide association study of prolactin levels in blood plasma and cerebrospinal fluid. BMC Genomics 17 Suppl 3:436|
|Staley, Lyndsay A; Ebbert, Mark T W; Bunker, Daniel et al. (2016) Variants in ACPP are associated with cerebrospinal fluid Prostatic Acid Phosphatase levels. BMC Genomics 17 Suppl 3:439|
|Ingber, Adam P; Hassenstab, Jason; Fagan, Anne M et al. (2016) Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future ""Non-Cognitive"" Outcomes of Alzheimer's Disease. J Alzheimers Dis 52:1055-64|
|Gordon, Brian A; Blazey, Tyler; Su, Yi et al. (2016) Longitudinal Î²-Amyloid Deposition and Hippocampal Volume in Preclinical Alzheimer Disease and Suspected Non-Alzheimer Disease Pathophysiology. JAMA Neurol 73:1192-1200|
|Babulal, Ganesh M; Ghoshal, Nupur; Head, Denise et al. (2016) Mood Changes in Cognitively Normal Older Adults are Linked to Alzheimer Disease Biomarker Levels. Am J Geriatr Psychiatry 24:1095-1104|
|Jack Jr, Clifford R; Knopman, David S; ChÃ©telat, GaÃ«l et al. (2016) Suspected non-Alzheimer disease pathophysiology--concept and controversy. Nat Rev Neurol 12:117-24|
|Ebbert, Mark T W; Staley, Lyndsay A; Parker, Joshua et al. (2016) Variants in CCL16 are associated with blood plasma and cerebrospinal fluid CCL16 protein levels. BMC Genomics 17 Suppl 3:437|
|Lucey, Brendan P; Mcleland, Jennifer S; Toedebusch, Cristina D et al. (2016) Comparison of a single-channel EEG sleep study to polysomnography. J Sleep Res 25:625-635|
|Cummings, Jeffrey; Aisen, Paul S; DuBois, Bruno et al. (2016) Drug development in Alzheimer's disease: the path to 2025. Alzheimers Res Ther 8:39|
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