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, Dominantly Inherited Alzheimer Network, M. Edip Gurol & 4 others Mark A. van Buchem, Ralph Martins, Jasmeer P. Chhatwal, Steven M. Greenberg

Research output: Contribution to journalArticleResearchpeer-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;86:616–625.

LanguageEnglish
Pages616-625
Number of pages10
JournalAnnals of Neurology
Volume86
Issue number4
Early online date30 Jul 2019
DOIs
Publication statusPublished - Oct 2019

Fingerprint

Familial Cerebral Amyloid Angiopathy
Amyloid
Cerebrospinal Fluid
Positron-Emission Tomography
Alzheimer Disease
Mutation
Blood Vessels
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Cerebral Amyloid Angiopathy
Spinal Puncture
Amyloid Plaques
Cerebral Hemorrhage
Neurologic Manifestations

Cite this

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. https://doi.org/10.1002/ana.25560
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. ; Dominantly Inherited Alzheimer Network ; Gurol, M. Edip ; van Buchem, Mark A. ; Martins, Ralph ; Chhatwal, Jasmeer P. ; Greenberg, Steven M. / Amyloid imaging of Dutch-type hereditary cerebral amyloid angiopathy carriers. In: Annals of Neurology. 2019 ; Vol. 86, No. 4. pp. 616-625.
@article{589d678c601b4d5098a6309d6c891848,
title = "Amyloid imaging of Dutch-type hereditary cerebral amyloid angiopathy carriers",
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.",
author = "Schultz, {Aaron P.} and Kloet, {Reina W.} and Sohrabi, {Hamid R.} and {van der Weerd}, Louise and {van Rooden}, Sanneke and Wermer, {Marieke J. H.} and Moursel, {Laure Grand} and Maqsood Yaqub and {van Berckel}, {Bart N. M.} and Pratishtha Chatterjee and Gardener, {Samantha L.} and Kevin Taddei and Fagan, {Anne M.} and Benzinger, {Tammie L.} and Morris, {John C.} and Reisa Sperling and Keith Johnson and Bateman, {Randall J.} and {Dominantly Inherited Alzheimer Network} and Gurol, {M. Edip} and {van Buchem}, {Mark A.} and Ralph Martins and Chhatwal, {Jasmeer P.} and Greenberg, {Steven M.}",
year = "2019",
month = "10",
doi = "10.1002/ana.25560",
language = "English",
volume = "86",
pages = "616--625",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "Wiley-Liss, Wiley",
number = "4",

}

Schultz, AP, Kloet, RW, Sohrabi, HR, van der Weerd, L, van Rooden, S, Wermer, MJH, Moursel, LG, Yaqub, M, van Berckel, BNM, Chatterjee, P, Gardener, SL, Taddei, K, Fagan, AM, Benzinger, TL, Morris, JC, Sperling, R, Johnson, K, Bateman, RJ, Dominantly Inherited Alzheimer Network, Gurol, ME, van Buchem, MA, Martins, R, Chhatwal, JP & Greenberg, SM 2019, 'Amyloid imaging of Dutch-type hereditary cerebral amyloid angiopathy carriers', Annals of Neurology, vol. 86, no. 4, pp. 616-625. https://doi.org/10.1002/ana.25560

Amyloid imaging of Dutch-type hereditary cerebral amyloid angiopathy carriers. / 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.; Dominantly Inherited Alzheimer Network; Gurol, M. Edip; van Buchem, Mark A.; Martins, Ralph; Chhatwal, Jasmeer P.; Greenberg, Steven M.

In: Annals of Neurology, Vol. 86, No. 4, 10.2019, p. 616-625.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Amyloid imaging of Dutch-type hereditary cerebral amyloid angiopathy carriers

AU - Schultz, Aaron P.

AU - Kloet, Reina W.

AU - Sohrabi, Hamid R.

AU - van der Weerd, Louise

AU - van Rooden, Sanneke

AU - Wermer, Marieke J. H.

AU - Moursel, Laure Grand

AU - Yaqub, Maqsood

AU - van Berckel, Bart N. M.

AU - Chatterjee, Pratishtha

AU - Gardener, Samantha L.

AU - Taddei, Kevin

AU - Fagan, Anne M.

AU - Benzinger, Tammie L.

AU - Morris, John C.

AU - Sperling, Reisa

AU - Johnson, Keith

AU - Bateman, Randall J.

AU - Dominantly Inherited Alzheimer Network

AU - Gurol, M. Edip

AU - van Buchem, Mark A.

AU - Martins, Ralph

AU - Chhatwal, Jasmeer P.

AU - Greenberg, Steven M.

PY - 2019/10

Y1 - 2019/10

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85070664067&partnerID=8YFLogxK

U2 - 10.1002/ana.25560

DO - 10.1002/ana.25560

M3 - Article

VL - 86

SP - 616

EP - 625

JO - Annals of Neurology

T2 - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 4

ER -

Schultz AP, Kloet RW, Sohrabi HR, van der Weerd L, van Rooden S, Wermer MJH et al. Amyloid imaging of Dutch-type hereditary cerebral amyloid angiopathy carriers. Annals of Neurology. 2019 Oct;86(4):616-625. https://doi.org/10.1002/ana.25560