Alzheimer's Imaging Consortium

Locus Coeruleus (LC) is the earliest location for tauopathy and its decline is highly correlated with AD symptomatology. The LC-NE system produces functional adaptive changes in response to chronic stress. [¹¹C]MRB-PET allows in vivo quantification of NE transporter (NET) in humans. Our previous data (ages 25-55) demonstrated that African Americans (AA) had greater NET availability but with faster decline rate compared to whites (W), suggesting chronic lifetime discrimination/stress may contribute to health disparity. The goal of this study is to use a larger sample size and older cohort (55-75) to further compare age and race effects on NET.

Subjects underwent a 90-min dynamic [¹¹C]MRB-PET via simultaneous PET/MRI. The segmentation of ROIs and LC delineation using TSE-neuromelanin was established via registration of PET, MRI, and Freesurfer via Firevoxel (https://wp.nyu.edu/Firevoxel), Binding potential (BP_ND, index of specific binding) using MRTM2 (t*=20 min, k2'=0.022 min-1) and annual percent change (APC = 100 × (em - 1), m is slope) were calculated.

Participants (38 AA, age: 62.97±4.82; 23 W, age 64.63±5.71) were included in our old cohort. In young cohort, avg BP_ND values of ROIs (16) from AA (age 34±7) were consistently higher than those from W (Figure 1), while in old cohort, BP_ND in LC, thalamus, hippocampus, amygdala from AA remains higher, and the group difference was reduced (Figure 2). In young cohort adults, all ROIs showed larger negative APC in BP_ND for AA, particularly in AA-M, e.g., -3%/yr in LTH & RAmyg and -1%/yr in BS & ROfac; while -0.1 & -0.12%/yr in BS & ROfac for W. However, in old cohort, only LC and olfactory bulb showed larger negative APC in AA. Figure 3 illustrates that AA had a steeper decline in LC (slope -0.026) vs W (-0.002).

NET availability is higher in young AA and declines faster in old AA. These two competing factors result in a reduced group difference seen in old cohort. We demonstrate that LC-NE function is sensitive to both age and stress effects and confirm that [¹¹C]MRB-PET is a promising strategy for early detection of underlying mechanisms for the health disparity in preclinical AD.