Fig. 3: Example images representing each of the PET and MRI modalities across the DIAN-OBS.

These images are depictions of a representative from each of our participant groups: non-carriers, mutation carriers—asymptomatic and mutation carriers—symptomatic (n = 3). In PiB-PET images, increases in uptake of the PiB tracer reflect increased amyloid deposits. In FDGPET, decreases in tracer uptake are indicative of reduced glucose metabolism (hypometabolism). For tau-PET imaging, increases in tracer uptake represent increases in tau deposits. Together, these three PET measures show greater AD pathology (amyloid deposits, hypometabolism and tau deposits) in this symptomatic mutation carrier compared to the asymptomatic mutation carrier and the control. In contrast, our MRI protocols do not measure tracer uptake, with each MR modality tailored to provide information about specific brain structures or function. T1w images are collected to assess structural morphometry, such as gray matter thickness and volume. Of note, our symptomatic mutation carrier appears to have larger ventricles and greater atrophy of the cortical ribbon compared to our representative asymptomatic mutation carrier and control. DWIs are collected to assess white matter integrity. Red, green and blue colors depict the primary direction of fiber orientation within each voxel, allowing assessment of microstructural changes in white matter. T2-FLAIR images are collected to assess white matter hyperintensities and edema. Here, several bright-white lesions can be visualized in the symptomatic mutation carrier. T2-Star, or susceptibility-weighted images, can be used to evaluate hemorrhagic lesions, such as the presence and location of cerebral microbleeds, which are common in ADAD. These can be visualized in the example symptomatic mutation carrier as small black dots. rsMRI is derived from functional MRI scans and can be used to measure the integrity of functional brain networks. These are thought to be disrupted in association with ADAD disease stage. Here, the default mode network is represented, revealing fewer regions of highly coherent activity fluctuations in the symptomatic mutation carrier. T2-FSE images are collected to quickly assess large deviations from expected structural morphometry (that is, tumors). Finally, ASL images are collected to assess cerebral perfusion. Deriving maps of perfusion allow quantification of the rate of cerebral blood flow, which is thought to decrease as a function of ADAD disease stage.