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Amyloid Imaging of Dutch-Type Hereditary Cerebral Amyloid Angiopathy Carriers

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, etc.

Ann Neurol. 2019 Oct;86(4):616-625.

PMID: 31361916

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP64005909	PiB		64005-90-9	Price

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