The influence of β-amyloid on [ 18 F]AV-1451 in semantic variant of primary progressive aphasia

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

OBJECTIVE: To compare [18F]AV-1451 uptake in the semantic variant of primary progressive aphasia (svPPA) to Alzheimer dementia, and determine whether increased uptake in svPPA is associated with the presence of β-amyloid (Aβ). METHODS: Thirty-one participants with svPPA underwent MRI and Pittsburgh compound B-PET scanning, and 17 of these also underwent [18F]AV-1451 tau-PET. A global Pittsburgh compound B standardized uptake value ratio was calculated for all participants, with a cutoff of 1.42 used to define Aβ(+) participants. We assessed region and voxel-level [18F]AV-1451 uptake in the whole svPPA cohort and separately in Aβ(+) and Aβ(-) svPPA groups, compared to 12 Aβ(+) participants with Alzheimer dementia and 170 cognitively normal, Aβ(-) controls. RESULTS: Of the entire cohort of participants with svPPA, 26% were Aβ(+). The Aβ(+) participants were older at scan compared to the Aβ(-) participants. svPPA showed elevated [18F]AV-1451 uptake in anteromedial temporal regions but the degree of uptake was lower than in Alzheimer dementia. After controlling for age, Aβ(+) status in svPPA was associated with significantly higher uptake in all anteromedial and inferior/middle lateral temporal regions, but uptake was still lower than in Alzheimer dementia. CONCLUSION: Although [18F]AV-1451 uptake is focally elevated in svPPA, the level of uptake is much less than what occurs in Alzheimer dementia and appears to be at least partially related to Aβ. Therefore, it is possible that some of the increased uptake of [18F]AV-1451 in svPPA is related to binding paired helical filament tau.

Original languageEnglish (US)
Pages (from-to)e710-e722
JournalNeurology
Volume92
Issue number7
DOIs
StatePublished - Feb 12 2019

Fingerprint

Primary Progressive Aphasia
Semantics
Amyloid
Alzheimer Disease
Temporal Lobe
7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

@article{d70b8733faf144e093551d1027e1d2bf,
title = "The influence of β-amyloid on [ 18 F]AV-1451 in semantic variant of primary progressive aphasia",
abstract = "OBJECTIVE: To compare [18F]AV-1451 uptake in the semantic variant of primary progressive aphasia (svPPA) to Alzheimer dementia, and determine whether increased uptake in svPPA is associated with the presence of β-amyloid (Aβ). METHODS: Thirty-one participants with svPPA underwent MRI and Pittsburgh compound B-PET scanning, and 17 of these also underwent [18F]AV-1451 tau-PET. A global Pittsburgh compound B standardized uptake value ratio was calculated for all participants, with a cutoff of 1.42 used to define Aβ(+) participants. We assessed region and voxel-level [18F]AV-1451 uptake in the whole svPPA cohort and separately in Aβ(+) and Aβ(-) svPPA groups, compared to 12 Aβ(+) participants with Alzheimer dementia and 170 cognitively normal, Aβ(-) controls. RESULTS: Of the entire cohort of participants with svPPA, 26{\%} were Aβ(+). The Aβ(+) participants were older at scan compared to the Aβ(-) participants. svPPA showed elevated [18F]AV-1451 uptake in anteromedial temporal regions but the degree of uptake was lower than in Alzheimer dementia. After controlling for age, Aβ(+) status in svPPA was associated with significantly higher uptake in all anteromedial and inferior/middle lateral temporal regions, but uptake was still lower than in Alzheimer dementia. CONCLUSION: Although [18F]AV-1451 uptake is focally elevated in svPPA, the level of uptake is much less than what occurs in Alzheimer dementia and appears to be at least partially related to Aβ. Therefore, it is possible that some of the increased uptake of [18F]AV-1451 in svPPA is related to binding paired helical filament tau.",
author = "Whitwell, {Jennifer Lynn} and Martin, {Peter R.} and Duffy, {Joseph R.} and Heather Clark and Machulda, {Mary Margaret} and Christopher Schwarz and Weigand, {Stephen D.} and Irene Sintini and Senjem, {Matthew L.} and Nilufer Taner and Hugo Botha and Rene Utianski and Jonathan Graff-Radford and Jones, {David T} and Boeve, {Bradley F} and Knopman, {David S} and Petersen, {Ronald Carl} and Jack, {Clifford R Jr.} and Val Lowe and Josephs, {Keith Anthony}",
year = "2019",
month = "2",
day = "12",
doi = "10.1212/WNL.0000000000006913",
language = "English (US)",
volume = "92",
pages = "e710--e722",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

TY - JOUR

T1 - The influence of β-amyloid on [ 18 F]AV-1451 in semantic variant of primary progressive aphasia

AU - Whitwell, Jennifer Lynn

AU - Martin, Peter R.

AU - Duffy, Joseph R.

AU - Clark, Heather

AU - Machulda, Mary Margaret

AU - Schwarz, Christopher

AU - Weigand, Stephen D.

AU - Sintini, Irene

AU - Senjem, Matthew L.

AU - Taner, Nilufer

AU - Botha, Hugo

AU - Utianski, Rene

AU - Graff-Radford, Jonathan

AU - Jones, David T

AU - Boeve, Bradley F

AU - Knopman, David S

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

AU - Lowe, Val

AU - Josephs, Keith Anthony

PY - 2019/2/12

Y1 - 2019/2/12

N2 - OBJECTIVE: To compare [18F]AV-1451 uptake in the semantic variant of primary progressive aphasia (svPPA) to Alzheimer dementia, and determine whether increased uptake in svPPA is associated with the presence of β-amyloid (Aβ). METHODS: Thirty-one participants with svPPA underwent MRI and Pittsburgh compound B-PET scanning, and 17 of these also underwent [18F]AV-1451 tau-PET. A global Pittsburgh compound B standardized uptake value ratio was calculated for all participants, with a cutoff of 1.42 used to define Aβ(+) participants. We assessed region and voxel-level [18F]AV-1451 uptake in the whole svPPA cohort and separately in Aβ(+) and Aβ(-) svPPA groups, compared to 12 Aβ(+) participants with Alzheimer dementia and 170 cognitively normal, Aβ(-) controls. RESULTS: Of the entire cohort of participants with svPPA, 26% were Aβ(+). The Aβ(+) participants were older at scan compared to the Aβ(-) participants. svPPA showed elevated [18F]AV-1451 uptake in anteromedial temporal regions but the degree of uptake was lower than in Alzheimer dementia. After controlling for age, Aβ(+) status in svPPA was associated with significantly higher uptake in all anteromedial and inferior/middle lateral temporal regions, but uptake was still lower than in Alzheimer dementia. CONCLUSION: Although [18F]AV-1451 uptake is focally elevated in svPPA, the level of uptake is much less than what occurs in Alzheimer dementia and appears to be at least partially related to Aβ. Therefore, it is possible that some of the increased uptake of [18F]AV-1451 in svPPA is related to binding paired helical filament tau.

AB - OBJECTIVE: To compare [18F]AV-1451 uptake in the semantic variant of primary progressive aphasia (svPPA) to Alzheimer dementia, and determine whether increased uptake in svPPA is associated with the presence of β-amyloid (Aβ). METHODS: Thirty-one participants with svPPA underwent MRI and Pittsburgh compound B-PET scanning, and 17 of these also underwent [18F]AV-1451 tau-PET. A global Pittsburgh compound B standardized uptake value ratio was calculated for all participants, with a cutoff of 1.42 used to define Aβ(+) participants. We assessed region and voxel-level [18F]AV-1451 uptake in the whole svPPA cohort and separately in Aβ(+) and Aβ(-) svPPA groups, compared to 12 Aβ(+) participants with Alzheimer dementia and 170 cognitively normal, Aβ(-) controls. RESULTS: Of the entire cohort of participants with svPPA, 26% were Aβ(+). The Aβ(+) participants were older at scan compared to the Aβ(-) participants. svPPA showed elevated [18F]AV-1451 uptake in anteromedial temporal regions but the degree of uptake was lower than in Alzheimer dementia. After controlling for age, Aβ(+) status in svPPA was associated with significantly higher uptake in all anteromedial and inferior/middle lateral temporal regions, but uptake was still lower than in Alzheimer dementia. CONCLUSION: Although [18F]AV-1451 uptake is focally elevated in svPPA, the level of uptake is much less than what occurs in Alzheimer dementia and appears to be at least partially related to Aβ. Therefore, it is possible that some of the increased uptake of [18F]AV-1451 in svPPA is related to binding paired helical filament tau.

UR - http://www.scopus.com/inward/record.url?scp=85061357876&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061357876&partnerID=8YFLogxK

U2 - 10.1212/WNL.0000000000006913

DO - 10.1212/WNL.0000000000006913

M3 - Article

C2 - 30635491

AN - SCOPUS:85061357876

VL - 92

SP - e710-e722

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 7

ER -