Amyloid imaging of dutch‐type hereditary cerebral amyloid angiopathy carriers

Objective To determine whether amyloid imaging with the positron emission tomography (PET) agent Pittsburgh compound B (PiB) can detect vascular β‐amyloid (Aβ) in the essentially pure form of cerebral amyloid angiopathy associated with the Dutch‐type hereditary cerebral amyloid angiopathy (D‐CAA) mutation. Methods PiB retention in a cortical composite of frontal, lateral, and retrosplenial regions (FLR) was measured by PiB‐PET in 19 D‐CAA mutation carriers (M + ; 13 without neurologic symptoms, 6 with prior lobar intracerebral hemorrhage) and 17 mutation noncarriers (M − ). Progression of PiB retention was analyzed in a subset of 18 serially imaged individuals (10 asymptomatic M + , 8 M − ). We also analyzed associations between PiB retention and cerebrospinal fluid (CSF) Aβ concentrations in 17 M + and 11 M − participants who underwent lumbar puncture and compared the findings to PiB‐PET and CSF Aβ in 37 autosomal dominant Alzheimer disease (ADAD) mutation carriers. Results D‐CAA M + showed greater age‐dependent FLR PiB retention ( p < 0.001) than M − , and serially imaged asymptomatic M + demonstrated greater longitudinal increases ( p = 0.004). Among M + , greater FLR PiB retention associated with reduced CSF concentrations of Aβ40 ( r = −0.55, p = 0.021) but not Aβ42 ( r = 0.01, p = 0.991). Despite comparably low CSF Aβ40 and Aβ42, PiB retention was substantially less in D‐CAA than ADAD ( p < 0.001). Interpretation Increased PiB retention in D‐CAA and correlation with reduced CSF Aβ40 suggest this compound labels vascular amyloid, although to a lesser degree than amyloid deposits in ADAD. Progression in PiB signal over time suggests amyloid PET as a potential biomarker in trials of candidate agents for this untreatable cause of hemorrhagic stroke. ANN NEUROL 2019;86:616–625