Brain imaging measurements of fibrillar amyloid-β burden, paired helical filament tau burden, and atrophy in cognitively unimpaired persons with two, one, and no copies of the APOE ε4 allele

Valentina Ghisays, Dhruman D. Goradia, Hillary Protas, Robert J. Bauer, Vivek Devadas, Pierre N. Tariot, Val J. Lowe, David S. Knopman, Ronald C. Petersen, Clifford R. Jack, Richard J. Caselli, Yi Su, Kewei Chen, Eric M. Reiman

Research output: Contribution to journalArticle

Abstract

Introduction: We previously characterized associations between brain imaging measurements of amyloid-β (Aβ) plaque burden and apolipoprotein E (APOE) ϵ4 gene dose in a small number of cognitively unimpaired late-middle-aged APOE ϵ4 homozygotes (HMs), heterozygotes (HTs), and noncarriers (NCs). We now characterize cross-sectional Aβ plaque, tau tangle, and cortical atrophy (neurodegeneration) measurements, classifications, and associations with age in a larger number of unimpaired HMs, HTs, and NCs over a wider age range. Methods: We analyzed 11C Pittsburgh compound B (Aβ) positron emission tomography (PET), flortaucipir (tau) PET, and volumetric magnetic resonance imaging data from 164 study participants of age 47–86 years, including 26 APOE ϵ4 HMs, 48 HTs, and 90 NCs matched for age and sex. Results: Aβ PET measurements rose, plateaued at the respective ages of 68 and 76, and then declined with age in unimpaired HM and HT groups. Compared with NCs, these two groups began to have significantly higher Aβ PET measurements at ages 62 and 70, respectively, and no longer had significantly higher measurements by ages 71 and 78, respectively. They began to have significantly higher entorhinal cortex tau PET measurements at ages 66 and 70, respectively, and no longer had significantly higher measurements by ages 74 and 78, respectively. Brain atrophy measurements tended to decline slowly with age in all three genetic groups. Their elevated tau PET measurements were attributable to those with positive Aβ PET scans. 41.0%, 18.0%, and 5.0% of the 47- to 70-year-old HMs, HTs, and NCs and 25.0%, 79.0%, and 38.0% of the 71- to 86-year-old HMs, HTs, and NCs had positive Aβ PET scans, and the long-term recall memory scores are significantly higher in the older HMs than in HT and NC groups, suggesting resistance to Aβ deposition in those HMs who remained unimpaired at older ages. Conclusions: This study provides information about Aβ plaque burden, tau tangle burden, and neurodegeneration in cognitively unimpaired persons at three levels of genetic risk for AD. Unimpaired APOE ϵ4 HMs can be studied before their 70s to evaluate the understanding of factors, processes, and interventions involved in the predisposition to and prevention of AD, and after their 70s, to discover factors, processes, and interventions involved in the resilience or resistance to and prevention of AD.

Original languageEnglish (US)
JournalAlzheimer's and Dementia
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Apolipoprotein E4
Homozygote
Amyloid
Neuroimaging
Atrophy
Positron-Emission Tomography
Heterozygote
Alleles
Entorhinal Cortex
Long-Term Memory
Amyloid Plaques
Magnetic Resonance Imaging

Keywords

  • Alzheimer's
  • Amyloid
  • APOE
  • Biomarkers
  • MRI
  • Neurodegeneration
  • PET
  • Prevention
  • Tau

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Brain imaging measurements of fibrillar amyloid-β burden, paired helical filament tau burden, and atrophy in cognitively unimpaired persons with two, one, and no copies of the APOE ε4 allele. / Ghisays, Valentina; Goradia, Dhruman D.; Protas, Hillary; Bauer, Robert J.; Devadas, Vivek; Tariot, Pierre N.; Lowe, Val J.; Knopman, David S.; Petersen, Ronald C.; Jack, Clifford R.; Caselli, Richard J.; Su, Yi; Chen, Kewei; Reiman, Eric M.

In: Alzheimer's and Dementia, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Introduction: We previously characterized associations between brain imaging measurements of amyloid-β (Aβ) plaque burden and apolipoprotein E (APOE) ϵ4 gene dose in a small number of cognitively unimpaired late-middle-aged APOE ϵ4 homozygotes (HMs), heterozygotes (HTs), and noncarriers (NCs). We now characterize cross-sectional Aβ plaque, tau tangle, and cortical atrophy (neurodegeneration) measurements, classifications, and associations with age in a larger number of unimpaired HMs, HTs, and NCs over a wider age range. Methods: We analyzed 11C Pittsburgh compound B (Aβ) positron emission tomography (PET), flortaucipir (tau) PET, and volumetric magnetic resonance imaging data from 164 study participants of age 47–86 years, including 26 APOE ϵ4 HMs, 48 HTs, and 90 NCs matched for age and sex. Results: Aβ PET measurements rose, plateaued at the respective ages of 68 and 76, and then declined with age in unimpaired HM and HT groups. Compared with NCs, these two groups began to have significantly higher Aβ PET measurements at ages 62 and 70, respectively, and no longer had significantly higher measurements by ages 71 and 78, respectively. They began to have significantly higher entorhinal cortex tau PET measurements at ages 66 and 70, respectively, and no longer had significantly higher measurements by ages 74 and 78, respectively. Brain atrophy measurements tended to decline slowly with age in all three genetic groups. Their elevated tau PET measurements were attributable to those with positive Aβ PET scans. 41.0{\%}, 18.0{\%}, and 5.0{\%} of the 47- to 70-year-old HMs, HTs, and NCs and 25.0{\%}, 79.0{\%}, and 38.0{\%} of the 71- to 86-year-old HMs, HTs, and NCs had positive Aβ PET scans, and the long-term recall memory scores are significantly higher in the older HMs than in HT and NC groups, suggesting resistance to Aβ deposition in those HMs who remained unimpaired at older ages. Conclusions: This study provides information about Aβ plaque burden, tau tangle burden, and neurodegeneration in cognitively unimpaired persons at three levels of genetic risk for AD. Unimpaired APOE ϵ4 HMs can be studied before their 70s to evaluate the understanding of factors, processes, and interventions involved in the predisposition to and prevention of AD, and after their 70s, to discover factors, processes, and interventions involved in the resilience or resistance to and prevention of AD.",
keywords = "Alzheimer's, Amyloid, APOE, Biomarkers, MRI, Neurodegeneration, PET, Prevention, Tau",
author = "Valentina Ghisays and Goradia, {Dhruman D.} and Hillary Protas and Bauer, {Robert J.} and Vivek Devadas and Tariot, {Pierre N.} and Lowe, {Val J.} and Knopman, {David S.} and Petersen, {Ronald C.} and Jack, {Clifford R.} and Caselli, {Richard J.} and Yi Su and Kewei Chen and Reiman, {Eric M.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.jalz.2019.08.195",
language = "English (US)",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
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TY - JOUR

T1 - Brain imaging measurements of fibrillar amyloid-β burden, paired helical filament tau burden, and atrophy in cognitively unimpaired persons with two, one, and no copies of the APOE ε4 allele

AU - Ghisays, Valentina

AU - Goradia, Dhruman D.

AU - Protas, Hillary

AU - Bauer, Robert J.

AU - Devadas, Vivek

AU - Tariot, Pierre N.

AU - Lowe, Val J.

AU - Knopman, David S.

AU - Petersen, Ronald C.

AU - Jack, Clifford R.

AU - Caselli, Richard J.

AU - Su, Yi

AU - Chen, Kewei

AU - Reiman, Eric M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Introduction: We previously characterized associations between brain imaging measurements of amyloid-β (Aβ) plaque burden and apolipoprotein E (APOE) ϵ4 gene dose in a small number of cognitively unimpaired late-middle-aged APOE ϵ4 homozygotes (HMs), heterozygotes (HTs), and noncarriers (NCs). We now characterize cross-sectional Aβ plaque, tau tangle, and cortical atrophy (neurodegeneration) measurements, classifications, and associations with age in a larger number of unimpaired HMs, HTs, and NCs over a wider age range. Methods: We analyzed 11C Pittsburgh compound B (Aβ) positron emission tomography (PET), flortaucipir (tau) PET, and volumetric magnetic resonance imaging data from 164 study participants of age 47–86 years, including 26 APOE ϵ4 HMs, 48 HTs, and 90 NCs matched for age and sex. Results: Aβ PET measurements rose, plateaued at the respective ages of 68 and 76, and then declined with age in unimpaired HM and HT groups. Compared with NCs, these two groups began to have significantly higher Aβ PET measurements at ages 62 and 70, respectively, and no longer had significantly higher measurements by ages 71 and 78, respectively. They began to have significantly higher entorhinal cortex tau PET measurements at ages 66 and 70, respectively, and no longer had significantly higher measurements by ages 74 and 78, respectively. Brain atrophy measurements tended to decline slowly with age in all three genetic groups. Their elevated tau PET measurements were attributable to those with positive Aβ PET scans. 41.0%, 18.0%, and 5.0% of the 47- to 70-year-old HMs, HTs, and NCs and 25.0%, 79.0%, and 38.0% of the 71- to 86-year-old HMs, HTs, and NCs had positive Aβ PET scans, and the long-term recall memory scores are significantly higher in the older HMs than in HT and NC groups, suggesting resistance to Aβ deposition in those HMs who remained unimpaired at older ages. Conclusions: This study provides information about Aβ plaque burden, tau tangle burden, and neurodegeneration in cognitively unimpaired persons at three levels of genetic risk for AD. Unimpaired APOE ϵ4 HMs can be studied before their 70s to evaluate the understanding of factors, processes, and interventions involved in the predisposition to and prevention of AD, and after their 70s, to discover factors, processes, and interventions involved in the resilience or resistance to and prevention of AD.

AB - Introduction: We previously characterized associations between brain imaging measurements of amyloid-β (Aβ) plaque burden and apolipoprotein E (APOE) ϵ4 gene dose in a small number of cognitively unimpaired late-middle-aged APOE ϵ4 homozygotes (HMs), heterozygotes (HTs), and noncarriers (NCs). We now characterize cross-sectional Aβ plaque, tau tangle, and cortical atrophy (neurodegeneration) measurements, classifications, and associations with age in a larger number of unimpaired HMs, HTs, and NCs over a wider age range. Methods: We analyzed 11C Pittsburgh compound B (Aβ) positron emission tomography (PET), flortaucipir (tau) PET, and volumetric magnetic resonance imaging data from 164 study participants of age 47–86 years, including 26 APOE ϵ4 HMs, 48 HTs, and 90 NCs matched for age and sex. Results: Aβ PET measurements rose, plateaued at the respective ages of 68 and 76, and then declined with age in unimpaired HM and HT groups. Compared with NCs, these two groups began to have significantly higher Aβ PET measurements at ages 62 and 70, respectively, and no longer had significantly higher measurements by ages 71 and 78, respectively. They began to have significantly higher entorhinal cortex tau PET measurements at ages 66 and 70, respectively, and no longer had significantly higher measurements by ages 74 and 78, respectively. Brain atrophy measurements tended to decline slowly with age in all three genetic groups. Their elevated tau PET measurements were attributable to those with positive Aβ PET scans. 41.0%, 18.0%, and 5.0% of the 47- to 70-year-old HMs, HTs, and NCs and 25.0%, 79.0%, and 38.0% of the 71- to 86-year-old HMs, HTs, and NCs had positive Aβ PET scans, and the long-term recall memory scores are significantly higher in the older HMs than in HT and NC groups, suggesting resistance to Aβ deposition in those HMs who remained unimpaired at older ages. Conclusions: This study provides information about Aβ plaque burden, tau tangle burden, and neurodegeneration in cognitively unimpaired persons at three levels of genetic risk for AD. Unimpaired APOE ϵ4 HMs can be studied before their 70s to evaluate the understanding of factors, processes, and interventions involved in the predisposition to and prevention of AD, and after their 70s, to discover factors, processes, and interventions involved in the resilience or resistance to and prevention of AD.

KW - Alzheimer's

KW - Amyloid

KW - APOE

KW - Biomarkers

KW - MRI

KW - Neurodegeneration

KW - PET

KW - Prevention

KW - Tau

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UR - http://www.scopus.com/inward/citedby.url?scp=85076246044&partnerID=8YFLogxK

U2 - 10.1016/j.jalz.2019.08.195

DO - 10.1016/j.jalz.2019.08.195

M3 - Article

AN - SCOPUS:85076246044

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

SN - 1552-5260

ER -