Changes in Aβ biomarkers and associations with APOE genotype in 2 longitudinal cohorts

Susan M. Resnick; Murat Bilgel; Abhay Moghekar; Yang An; Qing Cai; Mei Cheng Wang; Madhav Thambisetty; Jerry L. Prince; Yun Zhou; Anja Soldan; Dean F. Wong; Richard J. O'Brien; Luigi Ferrucci; Marilyn S. Albert

doi:10.1016/j.neurobiolaging.2015.04.001

Changes in Aβ biomarkers and associations with APOE genotype in 2 longitudinal cohorts

Susan M. Resnick, Murat Bilgel, Abhay Moghekar, Yang An, Qing Cai, Mei Cheng Wang, Madhav Thambisetty, Jerry L. Prince, Yun Zhou, Anja Soldan, Dean F. Wong, Richard J. O'Brien, Luigi Ferrucci, Marilyn S. Albert

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Abstract

Apolipoprotein E (APOE) genotype influences onset age of Alzheimer's disease but effects on disease progression are less clear. We investigated amyloid-β (Aβ) levels and change in relationship to APOE genotype, using 2 different measures of Aβ in 2 different longitudinal cohorts. Aβ accumulation was measured using positron emission tomography (PET) imaging and ¹¹C-Pittsburgh compound-B (PiB) in 113 Baltimore Longitudinal Study of Aging participants (mean age 77.3 years; 107 normal, 6 cognitively impaired) and cerebral spinal fluid (CSF) Aβ₁_-42 assays in 207 BIOCARD study participants (mean age 62 years; 195 normal, 12 cognitively impaired). Participants in both cohorts had up to 7 serial assessments (mean 2.3-2.4). PET-PiB retention increased and CSF Aβ_1-42 declined longitudinally. APOE ε4 was significantly associated with higher PET-PiB retention and lower CSF Aβ_1-42, independent of age and sex, but APOE genotype did not significantly affect Aβ change over time. APOE ε4 carriers may be further along in the disease process, consistent with earlier brain Aβ deposition and providing a biological basis for APOE genotype effects on onset age of Alzheimer's disease.

Original language	English (US)
Pages (from-to)	2333-2339
Number of pages	7
Journal	Neurobiology of aging
Volume	36
Issue number	8
DOIs	https://doi.org/10.1016/j.neurobiolaging.2015.04.001
State	Published - 2015

Keywords

Apolipoprotein E genotype
Biomarkers
CSF Aβ
Longitudinal
PET amyloid imaging

ASJC Scopus subject areas

General Neuroscience
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2015.04.001

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Resnick, S. M., Bilgel, M., Moghekar, A., An, Y., Cai, Q., Wang, M. C., Thambisetty, M., Prince, J. L., Zhou, Y., Soldan, A., Wong, D. F., O'Brien, R. J., Ferrucci, L., & Albert, M. S. (2015). Changes in Aβ biomarkers and associations with APOE genotype in 2 longitudinal cohorts. Neurobiology of aging, 36(8), 2333-2339. https://doi.org/10.1016/j.neurobiolaging.2015.04.001

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title = "Changes in Aβ biomarkers and associations with APOE genotype in 2 longitudinal cohorts",

abstract = "Apolipoprotein E (APOE) genotype influences onset age of Alzheimer's disease but effects on disease progression are less clear. We investigated amyloid-β (Aβ) levels and change in relationship to APOE genotype, using 2 different measures of Aβ in 2 different longitudinal cohorts. Aβ accumulation was measured using positron emission tomography (PET) imaging and 11C-Pittsburgh compound-B (PiB) in 113 Baltimore Longitudinal Study of Aging participants (mean age 77.3 years; 107 normal, 6 cognitively impaired) and cerebral spinal fluid (CSF) Aβ1-42 assays in 207 BIOCARD study participants (mean age 62 years; 195 normal, 12 cognitively impaired). Participants in both cohorts had up to 7 serial assessments (mean 2.3-2.4). PET-PiB retention increased and CSF Aβ1-42 declined longitudinally. APOE ε4 was significantly associated with higher PET-PiB retention and lower CSF Aβ1-42, independent of age and sex, but APOE genotype did not significantly affect Aβ change over time. APOE ε4 carriers may be further along in the disease process, consistent with earlier brain Aβ deposition and providing a biological basis for APOE genotype effects on onset age of Alzheimer's disease.",

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AU - Resnick, Susan M.

AU - Bilgel, Murat

AU - Moghekar, Abhay

AU - An, Yang

AU - Cai, Qing

AU - Wang, Mei Cheng

AU - Thambisetty, Madhav

AU - Prince, Jerry L.

AU - Zhou, Yun

AU - Soldan, Anja

AU - Wong, Dean F.

AU - O'Brien, Richard J.

AU - Ferrucci, Luigi

AU - Albert, Marilyn S.

PY - 2015

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AB - Apolipoprotein E (APOE) genotype influences onset age of Alzheimer's disease but effects on disease progression are less clear. We investigated amyloid-β (Aβ) levels and change in relationship to APOE genotype, using 2 different measures of Aβ in 2 different longitudinal cohorts. Aβ accumulation was measured using positron emission tomography (PET) imaging and 11C-Pittsburgh compound-B (PiB) in 113 Baltimore Longitudinal Study of Aging participants (mean age 77.3 years; 107 normal, 6 cognitively impaired) and cerebral spinal fluid (CSF) Aβ1-42 assays in 207 BIOCARD study participants (mean age 62 years; 195 normal, 12 cognitively impaired). Participants in both cohorts had up to 7 serial assessments (mean 2.3-2.4). PET-PiB retention increased and CSF Aβ1-42 declined longitudinally. APOE ε4 was significantly associated with higher PET-PiB retention and lower CSF Aβ1-42, independent of age and sex, but APOE genotype did not significantly affect Aβ change over time. APOE ε4 carriers may be further along in the disease process, consistent with earlier brain Aβ deposition and providing a biological basis for APOE genotype effects on onset age of Alzheimer's disease.

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KW - Biomarkers

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KW - Longitudinal

KW - PET amyloid imaging

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Changes in Aβ biomarkers and associations with APOE genotype in 2 longitudinal cohorts

Abstract

Keywords

ASJC Scopus subject areas

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