PET imaging with the Tau radioligand AV-1451 was introduced into the BLSA study in 2016. In combination with PET amyloid imaging and MRI measures, these studies will provide information on the preclinical stages of Alzheimer's Disease. Through August 25, 2019, 110 participants have had at least one PET Tau scan, and of these, 60 participants have had 2 or more scans. A customized analysis pipeline has been developed with refined MRI-based regions using the MUSE analysis for structural MRI region of interest definition. PET images are acquired on a High Resolution Research Tomograph for PET brain imaging and transferred to the Laboratory of Behavioral Neuroscience for analysis. Preliminary analysis of the first 60 images show the expected finding of greater Tau deposition in individuals with positive amyloid PET scans. In addition, associations of extracerebral off-target binding with age have been demonstrated. All participants enrolled in the BLSA PET Tau scan study also have an amyloid PET scan in addition to cognitive, motor and other BLSA assessments. The enrollment of BLSA participants into the PET Tau imaging study and analysis of additional images continues. In an initial publication (Alzheimer's & Dementia, DADM in press), we used 18F-AV-1451 (18F-Flortaucipir) PET to measure tau pathology in 54 cognitively normal BLSA participants (mean age 77.5, SD 8.9). We examined associations between PET radiotracer retention and age, sex, race, and amyloid positivity. We also investigated relationships between regional radiotracer retention and retrospective rates of change in regional volumes and cognitive function adjusting for age, sex, and amyloid status (positive vs negative). Greater age, male sex, black race, and amyloid positivity were associated with higher 18FAV-1451 retention in distinct brain regions. Retention in the entorhinal cortex was associated with lower entorhinal volume (p < 0.05) and a steeper decline in memory performance (p < 0.05). Assessment of medial temporal tau pathology will provide insights into structural brain changes in preclinical Alzheimer's disease that may predict later cognitive impairment and Alzheimer's disease. During this timeframe, we also assisted our Johns Hopkins collaborators on the development of a new Tau PET radiotracer (Wong et al, J Nuc Med 2018).

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000341-03
Application #
10017610
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Budget End
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
National Institute on Aging
Department
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