TY - JOUR
T1 - Cerebral Amyloid Angiopathy Pathology and Its Association With Amyloid-β PET Signal
AU - McCarter, Stuart J.
AU - Lesnick, Timothy G.
AU - Lowe, Val
AU - Mielke, Michelle M.
AU - Constantopoulos, Eleni
AU - Rabinstein, Alejandro A.
AU - Przybelski, Scott A.
AU - Botha, Hugo
AU - Jones, David T.
AU - Ramanan, Vijay K.
AU - Jack, Clifford R.
AU - Petersen, Ronald C.
AU - Knopman, David
AU - Boeve, Bradley F.
AU - Murray, Melissa E.
AU - Dickson, Dennis W.
AU - Vemuri, Prashanthi
AU - Kantarci, Kejal
AU - Reichard, R. Ross
AU - Graff-Radford, Jonathan
N1 - Publisher Copyright:
© American Academy of Neurology.
PY - 2021/11/2
Y1 - 2021/11/2
N2 - Background and ObjectivesTo determine the contribution of cerebral amyloid angiopathy (CAA) to Pittsburgh compound B (PiB)-PET tracer retention.MethodsParticipants from the Mayo Clinic Study of Aging and Mayo Clinic Alzheimer's Disease Research Center with antemortem PiB-PET imaging for β-amyloid (Aβ) who later underwent autopsy were included in this study. Pathologic regional leptomeningeal, parenchymal, capillary CAA, and Aβ plaque burden were calculated from one hemisphere. Regional lobar amyloid standardized uptake value ratio (SUVR) on PET was calculated from the same hemisphere sampled at autopsy. Single- and multiple-predictor linear regression models were used to evaluate the relative contributions of pathologically determined regional CAA and Aβ plaques to antemortem PiB-PET SUVR.ResultsForty-one participants (30 male, 11 female) with a mean (SD) age at death of 75.7 (10.6) years were included. Twenty-seven (66%) had high PiB signal with a mean (SD) of 2.3 (1.2) years from time of PET scan to death; 24 (59%) had a pathologic diagnosis of Alzheimer disease. On multivariate analysis, CAA was not associated with PiB-PET SUVR, while plaques remained associated with PiB-PET SUVR in all regions (all p < 0.05). In patients without frequent amyloid plaques, CAA was not associated with PiB-PET in any region.DiscussionWe did not find evidence that pathologically confirmed regional CAA burden contributes significantly to proximal antemortem regional PiB-PET signal, suggesting that amyloid PET imaging for measurement of cortical amyloid burden is unconfounded by CAA on a lobar level. Whether CAA burden contributes to PiB-PET signal in patients with severe CAA phenotypes, such as lobar hemorrhage, requires further investigation.
AB - Background and ObjectivesTo determine the contribution of cerebral amyloid angiopathy (CAA) to Pittsburgh compound B (PiB)-PET tracer retention.MethodsParticipants from the Mayo Clinic Study of Aging and Mayo Clinic Alzheimer's Disease Research Center with antemortem PiB-PET imaging for β-amyloid (Aβ) who later underwent autopsy were included in this study. Pathologic regional leptomeningeal, parenchymal, capillary CAA, and Aβ plaque burden were calculated from one hemisphere. Regional lobar amyloid standardized uptake value ratio (SUVR) on PET was calculated from the same hemisphere sampled at autopsy. Single- and multiple-predictor linear regression models were used to evaluate the relative contributions of pathologically determined regional CAA and Aβ plaques to antemortem PiB-PET SUVR.ResultsForty-one participants (30 male, 11 female) with a mean (SD) age at death of 75.7 (10.6) years were included. Twenty-seven (66%) had high PiB signal with a mean (SD) of 2.3 (1.2) years from time of PET scan to death; 24 (59%) had a pathologic diagnosis of Alzheimer disease. On multivariate analysis, CAA was not associated with PiB-PET SUVR, while plaques remained associated with PiB-PET SUVR in all regions (all p < 0.05). In patients without frequent amyloid plaques, CAA was not associated with PiB-PET in any region.DiscussionWe did not find evidence that pathologically confirmed regional CAA burden contributes significantly to proximal antemortem regional PiB-PET signal, suggesting that amyloid PET imaging for measurement of cortical amyloid burden is unconfounded by CAA on a lobar level. Whether CAA burden contributes to PiB-PET signal in patients with severe CAA phenotypes, such as lobar hemorrhage, requires further investigation.
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U2 - 10.1212/WNL.0000000000012770
DO - 10.1212/WNL.0000000000012770
M3 - Article
C2 - 34504022
AN - SCOPUS:85121406620
SN - 0028-3878
VL - 97
SP - E1799-E1808
JO - Neurology
JF - Neurology
IS - 18
ER -