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Amyloid imaging of dutch‐type hereditary cerebral amyloid angiopathy carriers

Schultz, A.P., Kloet, R.W., Sohrabi, H.R.ORCID: 0000-0001-8017-8682, Weerd, L., Rooden, S., Wermer, M.J.H., Moursel, L.G., Yaqub, M., Berckel, B.N.M., Chatterjee, P., Gardener, S.L., Taddei, K., Fagan, A.M., Benzinger, T.L., Morris, J.C., Sperling, R., Johnson, K., Bateman, R.J., Gurol, M.E., Buchem, M.A., Martins, R., Chhatwal, J.P. and Greenberg, S.M. (2019) Amyloid imaging of dutch‐type hereditary cerebral amyloid angiopathy carriers. Annals of Neurology, 86 (4). pp. 616-625.

Link to Published Version: https://doi.org/10.1002/ana.25560
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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

Item Type: Journal Article
Publisher: Wiley
Copyright: © 2019 American Neurological Association
URI: http://researchrepository.murdoch.edu.au/id/eprint/55553
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