Neuropathologic heterogeneity does not impair florbetapir-positron emission tomography postmortem correlates

Brittany Dugger, Christopher M. Clark, Geidy Serrano, Monica Mariner, Barry J. Bedell, R. Edward Coleman, P. Murali Doraiswamy, Ming Lu, Adam S. Fleisher, Eric M. Reiman, Marwan N. Sabbagh, Carl H. Sadowsky, Julie A. Schneider, Simone P. Zehntner, Alan P. Carpenter, Abhinay D. Joshi, Mark A. Mintun, Michael J. Pontecorvo, Daniel M. Skovronsky, Lucia I. SueThomas G. Beach

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Neuropathologic heterogeneity is often present among Alzheimer disease (AD) patients. We sought to determine whether amyloid imaging measures of AD are affected by concurrent pathologies. Thirty-eight clinically and pathologically defined AD and 17 nondemented patients with quantitative florbetapir F-18 (F-AV-45) positron emission tomography (PET) imaging during life and postmortem histological β-amyloid quantification and neuropathologic examination were assessed. AD patients were divided on the basis of concurrent pathologies, including those with Lewy bodies (LBs) (n = 21), white matter rarefaction (n = 27), severe cerebral amyloid angiopathy (n = 11), argyrophilic grains (n = 5), and TAR DNA binding protein-43 inclusions (n = 18). Many patients exhibited more than 1 type of concurrent pathology. The ratio of cortical to cerebellar amyloid imaging signal (SUVr) and immunohistochemical β-amyloid load were analyzed in 6 cortical regions of interest. All AD subgroups had strong and significant correlations between SUVr and histological β-amyloid measures (p μ 0.001). All AD subgroups had significantly greater amyloid measures versus nondemented patients, and mean amyloid measures did not significantly differ between AD subgroups. When comparing AD cases with and without each pathology, AD cases with LBs had significantly lower SUVr measures versus AD cases without LBs (p = 0.002); there were no other paired comparison differences. These findings indicate that florbetapir-PET imaging is not confounded by neuropathological heterogeneity within AD.

Original languageEnglish (US)
Pages (from-to)72-80
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume73
Issue number1
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Positron-Emission Tomography
Alzheimer Disease
Amyloid
Lewy Bodies
Pathology
florbetapir
Cerebral Amyloid Angiopathy
Matched-Pair Analysis
DNA-Binding Proteins

Keywords

  • A-amyloid
  • Alzheimer disease
  • Argyrophilic grains
  • Autopsy
  • Cerebral amyloid angiopathy
  • Leuko-araiosis
  • Lewy bodies
  • PET imaging
  • Plaques
  • TDP-43
  • Vascular dementia
  • White matter.

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Neuropathologic heterogeneity does not impair florbetapir-positron emission tomography postmortem correlates. / Dugger, Brittany; Clark, Christopher M.; Serrano, Geidy; Mariner, Monica; Bedell, Barry J.; Coleman, R. Edward; Doraiswamy, P. Murali; Lu, Ming; Fleisher, Adam S.; Reiman, Eric M.; Sabbagh, Marwan N.; Sadowsky, Carl H.; Schneider, Julie A.; Zehntner, Simone P.; Carpenter, Alan P.; Joshi, Abhinay D.; Mintun, Mark A.; Pontecorvo, Michael J.; Skovronsky, Daniel M.; Sue, Lucia I.; Beach, Thomas G.

In: Journal of Neuropathology and Experimental Neurology, Vol. 73, No. 1, 01.01.2014, p. 72-80.

Research output: Contribution to journalArticle

Dugger, B, Clark, CM, Serrano, G, Mariner, M, Bedell, BJ, Coleman, RE, Doraiswamy, PM, Lu, M, Fleisher, AS, Reiman, EM, Sabbagh, MN, Sadowsky, CH, Schneider, JA, Zehntner, SP, Carpenter, AP, Joshi, AD, Mintun, MA, Pontecorvo, MJ, Skovronsky, DM, Sue, LI & Beach, TG 2014, 'Neuropathologic heterogeneity does not impair florbetapir-positron emission tomography postmortem correlates', Journal of Neuropathology and Experimental Neurology, vol. 73, no. 1, pp. 72-80. https://doi.org/10.1097/NEN.0000000000000028
Dugger, Brittany ; Clark, Christopher M. ; Serrano, Geidy ; Mariner, Monica ; Bedell, Barry J. ; Coleman, R. Edward ; Doraiswamy, P. Murali ; Lu, Ming ; Fleisher, Adam S. ; Reiman, Eric M. ; Sabbagh, Marwan N. ; Sadowsky, Carl H. ; Schneider, Julie A. ; Zehntner, Simone P. ; Carpenter, Alan P. ; Joshi, Abhinay D. ; Mintun, Mark A. ; Pontecorvo, Michael J. ; Skovronsky, Daniel M. ; Sue, Lucia I. ; Beach, Thomas G. / Neuropathologic heterogeneity does not impair florbetapir-positron emission tomography postmortem correlates. In: Journal of Neuropathology and Experimental Neurology. 2014 ; Vol. 73, No. 1. pp. 72-80.
@article{2767ac538e4748989e1835da922367b5,
title = "Neuropathologic heterogeneity does not impair florbetapir-positron emission tomography postmortem correlates",
abstract = "Neuropathologic heterogeneity is often present among Alzheimer disease (AD) patients. We sought to determine whether amyloid imaging measures of AD are affected by concurrent pathologies. Thirty-eight clinically and pathologically defined AD and 17 nondemented patients with quantitative florbetapir F-18 (F-AV-45) positron emission tomography (PET) imaging during life and postmortem histological β-amyloid quantification and neuropathologic examination were assessed. AD patients were divided on the basis of concurrent pathologies, including those with Lewy bodies (LBs) (n = 21), white matter rarefaction (n = 27), severe cerebral amyloid angiopathy (n = 11), argyrophilic grains (n = 5), and TAR DNA binding protein-43 inclusions (n = 18). Many patients exhibited more than 1 type of concurrent pathology. The ratio of cortical to cerebellar amyloid imaging signal (SUVr) and immunohistochemical β-amyloid load were analyzed in 6 cortical regions of interest. All AD subgroups had strong and significant correlations between SUVr and histological β-amyloid measures (p μ 0.001). All AD subgroups had significantly greater amyloid measures versus nondemented patients, and mean amyloid measures did not significantly differ between AD subgroups. When comparing AD cases with and without each pathology, AD cases with LBs had significantly lower SUVr measures versus AD cases without LBs (p = 0.002); there were no other paired comparison differences. These findings indicate that florbetapir-PET imaging is not confounded by neuropathological heterogeneity within AD.",
keywords = "A-amyloid, Alzheimer disease, Argyrophilic grains, Autopsy, Cerebral amyloid angiopathy, Leuko-araiosis, Lewy bodies, PET imaging, Plaques, TDP-43, Vascular dementia, White matter.",
author = "Brittany Dugger and Clark, {Christopher M.} and Geidy Serrano and Monica Mariner and Bedell, {Barry J.} and Coleman, {R. Edward} and Doraiswamy, {P. Murali} and Ming Lu and Fleisher, {Adam S.} and Reiman, {Eric M.} and Sabbagh, {Marwan N.} and Sadowsky, {Carl H.} and Schneider, {Julie A.} and Zehntner, {Simone P.} and Carpenter, {Alan P.} and Joshi, {Abhinay D.} and Mintun, {Mark A.} and Pontecorvo, {Michael J.} and Skovronsky, {Daniel M.} and Sue, {Lucia I.} and Beach, {Thomas G.}",
year = "2014",
month = "1",
day = "1",
doi = "10.1097/NEN.0000000000000028",
language = "English (US)",
volume = "73",
pages = "72--80",
journal = "American Journal of Psychotherapy",
issn = "0002-9564",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Neuropathologic heterogeneity does not impair florbetapir-positron emission tomography postmortem correlates

AU - Dugger, Brittany

AU - Clark, Christopher M.

AU - Serrano, Geidy

AU - Mariner, Monica

AU - Bedell, Barry J.

AU - Coleman, R. Edward

AU - Doraiswamy, P. Murali

AU - Lu, Ming

AU - Fleisher, Adam S.

AU - Reiman, Eric M.

AU - Sabbagh, Marwan N.

AU - Sadowsky, Carl H.

AU - Schneider, Julie A.

AU - Zehntner, Simone P.

AU - Carpenter, Alan P.

AU - Joshi, Abhinay D.

AU - Mintun, Mark A.

AU - Pontecorvo, Michael J.

AU - Skovronsky, Daniel M.

AU - Sue, Lucia I.

AU - Beach, Thomas G.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Neuropathologic heterogeneity is often present among Alzheimer disease (AD) patients. We sought to determine whether amyloid imaging measures of AD are affected by concurrent pathologies. Thirty-eight clinically and pathologically defined AD and 17 nondemented patients with quantitative florbetapir F-18 (F-AV-45) positron emission tomography (PET) imaging during life and postmortem histological β-amyloid quantification and neuropathologic examination were assessed. AD patients were divided on the basis of concurrent pathologies, including those with Lewy bodies (LBs) (n = 21), white matter rarefaction (n = 27), severe cerebral amyloid angiopathy (n = 11), argyrophilic grains (n = 5), and TAR DNA binding protein-43 inclusions (n = 18). Many patients exhibited more than 1 type of concurrent pathology. The ratio of cortical to cerebellar amyloid imaging signal (SUVr) and immunohistochemical β-amyloid load were analyzed in 6 cortical regions of interest. All AD subgroups had strong and significant correlations between SUVr and histological β-amyloid measures (p μ 0.001). All AD subgroups had significantly greater amyloid measures versus nondemented patients, and mean amyloid measures did not significantly differ between AD subgroups. When comparing AD cases with and without each pathology, AD cases with LBs had significantly lower SUVr measures versus AD cases without LBs (p = 0.002); there were no other paired comparison differences. These findings indicate that florbetapir-PET imaging is not confounded by neuropathological heterogeneity within AD.

AB - Neuropathologic heterogeneity is often present among Alzheimer disease (AD) patients. We sought to determine whether amyloid imaging measures of AD are affected by concurrent pathologies. Thirty-eight clinically and pathologically defined AD and 17 nondemented patients with quantitative florbetapir F-18 (F-AV-45) positron emission tomography (PET) imaging during life and postmortem histological β-amyloid quantification and neuropathologic examination were assessed. AD patients were divided on the basis of concurrent pathologies, including those with Lewy bodies (LBs) (n = 21), white matter rarefaction (n = 27), severe cerebral amyloid angiopathy (n = 11), argyrophilic grains (n = 5), and TAR DNA binding protein-43 inclusions (n = 18). Many patients exhibited more than 1 type of concurrent pathology. The ratio of cortical to cerebellar amyloid imaging signal (SUVr) and immunohistochemical β-amyloid load were analyzed in 6 cortical regions of interest. All AD subgroups had strong and significant correlations between SUVr and histological β-amyloid measures (p μ 0.001). All AD subgroups had significantly greater amyloid measures versus nondemented patients, and mean amyloid measures did not significantly differ between AD subgroups. When comparing AD cases with and without each pathology, AD cases with LBs had significantly lower SUVr measures versus AD cases without LBs (p = 0.002); there were no other paired comparison differences. These findings indicate that florbetapir-PET imaging is not confounded by neuropathological heterogeneity within AD.

KW - A-amyloid

KW - Alzheimer disease

KW - Argyrophilic grains

KW - Autopsy

KW - Cerebral amyloid angiopathy

KW - Leuko-araiosis

KW - Lewy bodies

KW - PET imaging

KW - Plaques

KW - TDP-43

KW - Vascular dementia

KW - White matter.

UR - http://www.scopus.com/inward/record.url?scp=84891827346&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891827346&partnerID=8YFLogxK

U2 - 10.1097/NEN.0000000000000028

DO - 10.1097/NEN.0000000000000028

M3 - Article

AN - SCOPUS:84891827346

VL - 73

SP - 72

EP - 80

JO - American Journal of Psychotherapy

JF - American Journal of Psychotherapy

SN - 0002-9564

IS - 1

ER -