APOE genotype and early β-amyloid accumulation in older adults without dementia

Yen Ying Lim; Elizabeth C Mormino; Alzheimer's Disease Neuroimaging Initiative

doi:10.1212/WNL.0000000000004336

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APOE genotype and early β-amyloid accumulation in older adults without dementia

Journal article

Open access

Peer reviewed

APOE genotype and early β-amyloid accumulation in older adults without dementia

Yen Ying Lim, Elizabeth C Mormino and Alzheimer's Disease Neuroimaging Initiative

Neurology, Vol.89(10), pp.1028-1034

09/05/2017

DOI: 10.1212/WNL.0000000000004336

PMCID: PMC5589795

PMID: 28794245

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Abstract

To clarify associations between ε4 allele and age on longitudinal rates of β-amyloid (Aβ) accumulation within Aβ+ and Aβ- older individuals without dementia. We analyzed 595 older adults without dementia classified cross-sectionally as Aβ- (n = 325) and Aβ+ (n = 270) using longitudinal florbetapir PET. The influence of age and genotype on longitudinal accumulation of Aβ was examined with linear mixed models. ε4 and older age were associated with higher risk of being classified as Aβ+ at baseline. The annual rate of Aβ accumulation was significantly greater than zero for Aβ- ε3 (0.0021 ± 0.0007 standardized uptake value ratio [SUVR] units) and Aβ- ε4 (0.0044 ± 0.0010 SUVR units), as well as Aβ+ ε3 (0.0141 ± 0.0019 SUVR units) and Aβ+ ε4 (0.0126 ± 0.0018 SUVR units). Aβ accumulation was significantly faster in Aβ- ε4 compared to Aβ- ε3 and Aβ- ε2. Rates of Aβ accumulation did not differ significantly between Aβ+ groups. Older age was associated with higher rates of Aβ accumulation in the Aβ- group. ε4 carriage and older age were predictors of longitudinal Aβ accumulation within the Aβ- group but not the Aβ+ group. ε2 carriage was protective against longitudinal Aβ accumulation within the Aβ- group. genotype in conjunction with chronologic age may aid in participant selection for primary prevention trials aimed at halting Aβ accumulation before abnormal levels are reached.

Brain - diagnostic imaging

Apolipoprotein E4 - genetics

Cross-Sectional Studies

Apolipoprotein E2 - genetics

Superior Sagittal Sinus

Aniline Compounds

Humans

Risk Factors

Linear Models

Male

Positron-Emission Tomography

Brain - metabolism

Apolipoprotein E3 - genetics

Aging - genetics

Ethylene Glycols

Amyloid beta-Peptides - metabolism

Female

Heterozygote

Aged

Radiopharmaceuticals

Aging - metabolism

Details

Title: Subtitle: APOE genotype and early β-amyloid accumulation in older adults without dementia
Creators: Yen Ying Lim - From the Florey Institute of Neuroscience and Mental Health (Y.Y.L.), The University of Melbourne, Parkville, Australia; and the Department of Neurology and Neurological Sciences (E.C.M.), Stanford University, CA
Elizabeth C Mormino - From the Florey Institute of Neuroscience and Mental Health (Y.Y.L.), The University of Melbourne, Parkville, Australia; and the Department of Neurology and Neurological Sciences (E.C.M.), Stanford University, CA. bmormino@stanford.edu
Alzheimer's Disease Neuroimaging Initiative
Contributors: Laura L Boles-Ponto (Contributor) - University of Iowa, Radiology
Resource Type: Journal article
Publication Details: Neurology, Vol.89(10), pp.1028-1034
DOI: 10.1212/WNL.0000000000004336
PMID: 28794245
PMCID: PMC5589795
NLM abbreviation: Neurology
ISSN: 0028-3878
eISSN: 1526-632X
Publisher: United States
Grant note: P50 AG047366 / NIA NIH HHS P30 AG010129 / NIA NIH HHS P41 EB015922 / NIBIB NIH HHS K01 AG051718 / NIA NIH HHS
Language: English
Date published: 09/05/2017
Academic Unit: Radiology; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984051520102771

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