Pittsburgh Compound B and AV-1451 positron emission tomography assessment of molecular pathologies of Alzheimer's disease in progressive supranuclear palsy

Jennifer Lynn Whitwell, J. Eric Ahlskog, Nirubol Tosakulwong, Matthew L. Senjem, Anthony J. Spychalla, Ronald Carl Petersen, Clifford R Jr. Jack, Val Lowe, Keith Anthony Josephs

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10 Citations (Scopus)

Abstract

Introduction: Little is known about Alzheimer's disease molecular proteins, beta-amyloid and paired helical filament (PHF) tau, in progressive supranuclear palsy (PSP). Recent techniques have been developed to allow for investigations of these proteins in PSP. We determined the frequency of beta-amyloid deposition in PSP, and whether beta-amyloid deposition in PSP is associated with PHF-tau deposition pattern, or clinical features. Methods: Thirty probable PSP participants underwent MRI, [18F]AV-1451 PET and Pittsburgh compound B (PiB) PET. Apolipoprotein (APOE) genotyping was also performed. A global PiB standard-uptake value ratio (SUVR) was calculated. AV-1451 SUVRs were calculated for a set of Alzheimer's disease (AD)-related regions and a set of PSP-related regions. Voxel-level analyses were conducted to assess for differences in AV-1451 uptake patterns and MRI atrophy between PiB(+) and PiB(-) cases compared to 60 normal PiB(-) controls. Statistical testing for correlations and associations between variables of interest were also performed. Results: Twelve subjects (40%) showed beta-amyloid deposition. Higher PiB SUVR correlated with older age but not with AV-1451 SUVR in the AD- or PSP-related regions. Higher AV-1451 SUVR in AD-related regions was associated with higher AV-1451 SUVR in PSP-related regions. We found little evidence for beta-amyloid related differences in clinical metrics, proportion of APOE e4 carriers, pattern of AV-1451 uptake, or pattern of atrophy. Conclusion: Beta-amyloid deposition occurs in a relatively high proportion of PSP subjects. Unlike in Alzheimer's disease, however, there is little evidence that beta-amyloid, and PHF-tau, play a significant role in neurodegeneration in PSP.

Original languageEnglish (US)
JournalParkinsonism and Related Disorders
DOIs
StateAccepted/In press - Jan 1 2017

Fingerprint

Progressive Supranuclear Palsy
Molecular Pathology
Positron-Emission Tomography
Alzheimer Disease
Amyloid
Atrophy
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Apolipoprotein E4
Apolipoproteins
Amyloid beta-Peptides

Keywords

  • AV1451
  • Beta-amyloid
  • PiB
  • PSP
  • Tau
  • Tau-PET

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

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title = "Pittsburgh Compound B and AV-1451 positron emission tomography assessment of molecular pathologies of Alzheimer's disease in progressive supranuclear palsy",
abstract = "Introduction: Little is known about Alzheimer's disease molecular proteins, beta-amyloid and paired helical filament (PHF) tau, in progressive supranuclear palsy (PSP). Recent techniques have been developed to allow for investigations of these proteins in PSP. We determined the frequency of beta-amyloid deposition in PSP, and whether beta-amyloid deposition in PSP is associated with PHF-tau deposition pattern, or clinical features. Methods: Thirty probable PSP participants underwent MRI, [18F]AV-1451 PET and Pittsburgh compound B (PiB) PET. Apolipoprotein (APOE) genotyping was also performed. A global PiB standard-uptake value ratio (SUVR) was calculated. AV-1451 SUVRs were calculated for a set of Alzheimer's disease (AD)-related regions and a set of PSP-related regions. Voxel-level analyses were conducted to assess for differences in AV-1451 uptake patterns and MRI atrophy between PiB(+) and PiB(-) cases compared to 60 normal PiB(-) controls. Statistical testing for correlations and associations between variables of interest were also performed. Results: Twelve subjects (40{\%}) showed beta-amyloid deposition. Higher PiB SUVR correlated with older age but not with AV-1451 SUVR in the AD- or PSP-related regions. Higher AV-1451 SUVR in AD-related regions was associated with higher AV-1451 SUVR in PSP-related regions. We found little evidence for beta-amyloid related differences in clinical metrics, proportion of APOE e4 carriers, pattern of AV-1451 uptake, or pattern of atrophy. Conclusion: Beta-amyloid deposition occurs in a relatively high proportion of PSP subjects. Unlike in Alzheimer's disease, however, there is little evidence that beta-amyloid, and PHF-tau, play a significant role in neurodegeneration in PSP.",
keywords = "AV1451, Beta-amyloid, PiB, PSP, Tau, Tau-PET",
author = "Whitwell, {Jennifer Lynn} and Ahlskog, {J. Eric} and Nirubol Tosakulwong and Senjem, {Matthew L.} and Spychalla, {Anthony J.} and Petersen, {Ronald Carl} and Jack, {Clifford R Jr.} and Val Lowe and Josephs, {Keith Anthony}",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.parkreldis.2017.12.016",
language = "English (US)",
journal = "Parkinsonism and Related Disorders",
issn = "1353-8020",
publisher = "Elsevier BV",

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TY - JOUR

T1 - Pittsburgh Compound B and AV-1451 positron emission tomography assessment of molecular pathologies of Alzheimer's disease in progressive supranuclear palsy

AU - Whitwell, Jennifer Lynn

AU - Ahlskog, J. Eric

AU - Tosakulwong, Nirubol

AU - Senjem, Matthew L.

AU - Spychalla, Anthony J.

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

AU - Lowe, Val

AU - Josephs, Keith Anthony

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Introduction: Little is known about Alzheimer's disease molecular proteins, beta-amyloid and paired helical filament (PHF) tau, in progressive supranuclear palsy (PSP). Recent techniques have been developed to allow for investigations of these proteins in PSP. We determined the frequency of beta-amyloid deposition in PSP, and whether beta-amyloid deposition in PSP is associated with PHF-tau deposition pattern, or clinical features. Methods: Thirty probable PSP participants underwent MRI, [18F]AV-1451 PET and Pittsburgh compound B (PiB) PET. Apolipoprotein (APOE) genotyping was also performed. A global PiB standard-uptake value ratio (SUVR) was calculated. AV-1451 SUVRs were calculated for a set of Alzheimer's disease (AD)-related regions and a set of PSP-related regions. Voxel-level analyses were conducted to assess for differences in AV-1451 uptake patterns and MRI atrophy between PiB(+) and PiB(-) cases compared to 60 normal PiB(-) controls. Statistical testing for correlations and associations between variables of interest were also performed. Results: Twelve subjects (40%) showed beta-amyloid deposition. Higher PiB SUVR correlated with older age but not with AV-1451 SUVR in the AD- or PSP-related regions. Higher AV-1451 SUVR in AD-related regions was associated with higher AV-1451 SUVR in PSP-related regions. We found little evidence for beta-amyloid related differences in clinical metrics, proportion of APOE e4 carriers, pattern of AV-1451 uptake, or pattern of atrophy. Conclusion: Beta-amyloid deposition occurs in a relatively high proportion of PSP subjects. Unlike in Alzheimer's disease, however, there is little evidence that beta-amyloid, and PHF-tau, play a significant role in neurodegeneration in PSP.

AB - Introduction: Little is known about Alzheimer's disease molecular proteins, beta-amyloid and paired helical filament (PHF) tau, in progressive supranuclear palsy (PSP). Recent techniques have been developed to allow for investigations of these proteins in PSP. We determined the frequency of beta-amyloid deposition in PSP, and whether beta-amyloid deposition in PSP is associated with PHF-tau deposition pattern, or clinical features. Methods: Thirty probable PSP participants underwent MRI, [18F]AV-1451 PET and Pittsburgh compound B (PiB) PET. Apolipoprotein (APOE) genotyping was also performed. A global PiB standard-uptake value ratio (SUVR) was calculated. AV-1451 SUVRs were calculated for a set of Alzheimer's disease (AD)-related regions and a set of PSP-related regions. Voxel-level analyses were conducted to assess for differences in AV-1451 uptake patterns and MRI atrophy between PiB(+) and PiB(-) cases compared to 60 normal PiB(-) controls. Statistical testing for correlations and associations between variables of interest were also performed. Results: Twelve subjects (40%) showed beta-amyloid deposition. Higher PiB SUVR correlated with older age but not with AV-1451 SUVR in the AD- or PSP-related regions. Higher AV-1451 SUVR in AD-related regions was associated with higher AV-1451 SUVR in PSP-related regions. We found little evidence for beta-amyloid related differences in clinical metrics, proportion of APOE e4 carriers, pattern of AV-1451 uptake, or pattern of atrophy. Conclusion: Beta-amyloid deposition occurs in a relatively high proportion of PSP subjects. Unlike in Alzheimer's disease, however, there is little evidence that beta-amyloid, and PHF-tau, play a significant role in neurodegeneration in PSP.

KW - AV1451

KW - Beta-amyloid

KW - PiB

KW - PSP

KW - Tau

KW - Tau-PET

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U2 - 10.1016/j.parkreldis.2017.12.016

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