Amyloid imaging of dutch-type hereditary cerebral amyloid angiopathy carriers

Authors/Creators

• Aaron P. Schultz
• Reina W. Kloet
• Hamid R. Sohrabi, Edith Cowan UniversityFollow
• 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, Edith Cowan UniversityFollow
• Kevin Taddei, Edith Cowan UniversityFollow
• Anne M. Fagan
• Tammie L. Benzinger
• John C. Morris
• Reisa Sperling
• Keith Johnson
• Randall J. Bateman
• Dominantly Inherited Alzheimer Network
• M. Edip Gurol
• Mark A. van Buchem
• Ralph Martins, Edith Cowan UniversityFollow
• Jasmeer P. Chhatwal
• Steven M. Greenberg

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.

Keywords

amyloid beta protein[1-40], amyloid beta protein[1-42], Pittsburgh compound B, adult, Article, brain hemorrhage, cerebrospinal fluid analysis, clinical article, cohort analysis, controlled study, female, gene mutation, genetic disorder, human, human tissue, lumbar puncture, male, middle aged, positron emission tomography, priority journal, staining, tissue section, vascular amyloidosis

Document Type

Journal Article

Date of Publication

2019

ISSN

1531-8249

Volume

86

Issue

4

PubMed ID

31361916

Publication Title

Annals of Neurology

Publisher

Wiley

School

School of Medical and Health Sciences

RAS ID

30040

Funders

This work was supported by the National Institute of Neurologic Diseases and Stroke (R01NS070834) and the Dominantly Inherited Alzheimer's Network (UF1AG032438), which is funded by the National Institute on Aging, the German Center for Neurodegenerative Diseases, and the Raul Carrea Institute for Neurological Research, with partial support from the Research and Development Grants for Dementia from the Japan Agency for Medical Research and Development and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute.

Comments

Schultz, A. P., Kloet, R. W., Sohrabi, H. R., van der Weerd, L., van Rooden, S., Wermer, M. J. H., ... & Greenberg, S. M. (2019). Amyloid imaging of dutch‐type hereditary cerebral amyloid angiopathy carriers. Annals of Neurology, 86(4), 616-625.

Available here.

Copyright

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First Page

616

Last Page

625