Amyloid imaging of dutch‐type hereditary cerebral amyloid angiopathy carriers. Issue 4 (12th August 2019)

• Record Type: Journal Article
• Authors: Schultz, Aaron P.; Kloet, Reina W.; Sohrabi, Hamid R.; van der Weerd, Louise; van Rooden, Sanneke; Wermer, Marieke J. H.; Moursel, Laure Grand; Yaqub, Maqsood; van Berckel, Bart N. M.; Chatterjee, Pratishtha; Gardener, Samantha L.; Taddei, Kevin; Fagan, Anne M.; Benzinger, Tammie L.; Morris, John C.; Sperling, Reisa; Johnson, Keith; Bateman, Randall J.; Gurol, M. Edip; van Buchem, Mark A.; Martins, Ralph; Chhatwal, Jasmeer P.; Greenberg, Steven M.
• Is Part Of: Annals of neurology. Volume 86:Issue 4(2019)
• Page Start: 616
• Page End: 625
• Publication Date: 2019-08-12
• Subjects: Neurology -- Periodicals; Pediatric neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; 616.8
• DOI: 10.1002/ana.25560
• Languages: English
• ISSNs: 0364-5134

Abstract

Abstract : 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