Abstract #4112

Delayed CSF clearance may provide a more sensitive disease marker than blood-CSF-barrier impairment in an Alzheimer’s disease mouse model

Yuhan Bian^1,2,3, Hannah Fuehrer⁴, Di Cao^1,2,3, Yuanqi Sun^1,2,3, Chunming Gu^1,2,3, Yinghao Li^1,2,3, Adnan Bibic², Yuguo Li², Jiangyang Zhang⁵, Linda Knutsson^2,3,6, Peter C.M. Van Zijl^1,2,3, Wanli Smith⁴, and Jun Hua^2,3

¹Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ³Neurosection, Division of MRI Research, Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, ⁴Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, United States, ⁵Center for Biomedical Imaging, NYU Grossman School of Medicine, New York, NY, United States, ⁶Department of Neurology, Johns Hopkins University, Baltimore, MD, United States

Synopsis

Keywords: Neurofluids, DSC & DCE Perfusion, Alzheimer' Disease; CSF clearance; GBCA

Motivation: Accumulation of abnormal proteins in AD has been linked with barrier breakdown between blood and tissue or CSF, and impaired clearance from the brain.

Goal(s): To use GBCA-induced signal changes in ventricular CSF following intravenous injection and its decay over time as indices to study the integrity of blood-CSF barrier (BCSFB) and GBCA clearance via CSF, respectively.

Approach: Dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI was performed in the 3xTg-AD mouse model.

Results: Impaired clearance in AD mice became significant at 8 months. The amount of GBCA crossing BCSFB appeared similar between AD and WT mice at these early stages.

Impact: Our results suggest that delayed CSF clearance may provide a more sensitive marker for AD, and parameters measured during the clearance phase may be more robust than measures obtained immediately after GBCA administration.

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