Amyloid imaging of dutch-type hereditary cerebral amyloid angiopathy carriers

Aaron P. Schultz, Reina W. Kloet, Hamid R. Sohrabi, Louise van der Weerd, Sanneke van Rooden, Marieke J. H. Wermer, Laure Grand Moursel, Maqsood Yaqub, Bart N. M. van Berckel, Pratishtha Chatterjee, Samantha L. Gardener, Kevin Taddei, Anne M. Fagan, Tammie L. Benzinger, John C. Morris, Reisa Sperling, Keith Johnson, Randall J. Bateman, M. Edip Gurol, Mark A. van BuchemRalph Martins, Jasmeer P. Chhatwal, Steven M. Greenberg, Dominantly Inherited Alzheimer Network

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Pages (from-to)616-625
JournalAnnals of Neurology
Volume86
Issue number4
DOIs
Publication statusPublished - 1 Oct 2019

Cite this

Schultz, A. P., Kloet, R. W., Sohrabi, H. R., van der Weerd, L., van Rooden, S., Wermer, M. J. H., ... Dominantly Inherited Alzheimer Network (2019). Amyloid imaging of dutch-type hereditary cerebral amyloid angiopathy carriers. Annals of Neurology, 86(4), 616-625. https://doi.org/10.1002/ana.25560