Associations between baseline amyloid, sex, and APOE on subsequent tau accumulation in cerebrospinal fluid

NEUROBIOLOGY OF AGING

卷:78

Article

Buckley, Rachel F.^1,2,3  Mormino, Elizabeth C.⁴  Chhatwal, Jasmeer^3,5  Schultz, Aaron P.^3,6  Rabin, Jennifer S.^7,8  Rentz, Dorene M.^3,5  Acar, Diler⁹  Properzi, Michael J.¹⁰  Dumurgier, Julien¹⁰  Jacobs, Heidi^8,10,11  Gomez-Isla, Teresa^3,12  Johnson, Keith A.^5,6,8,10,13  Sperling, Reisa A.^3,5  Hanseeuw, Bernard J.^3,8,14,15 

[1] Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia

[2] Univ Melbourne, Melbourne Sch Psychol Sci, Melbourne, Vic, Australia

[3] Harvard Med Sch, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA

[4] Stanford Univ, Dept Neurol & Neurol Sci, Santa Clara County, CA USA

[5] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, 75 Francis St, Boston, MA 02115 USA

[6] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA

[7] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA

[8] Harvard Med Sch, Boston, MA 02115 USA

[9] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA

[10] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

[11] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA USA

[12] Massachusetts Alzheimers Dis Res Ctr, Boston, MA USA

[13] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA

[14] Massachusetts Gen Hosp, Dept Radiol, Gordon Ctr Med Imaging, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA

[15] Clin Univ St Luc, Dept Neurol, Brussels, Belgium

关键词: Cerebrospinal fluid;    Alzheimer's disease;    Amyloid;    tau;    APOE;    Sex;   

DOI  :  10.1016/j.neurobiolaging.2019.02.019

来源: Elsevier

【 摘 要 】

We investigated the effect of baseline A beta, sex, and APOE on longitudinal tau accumulation in cerebrospinal fluid (CSF) in clinically normal older adults. Two hundred thirty-nine participants (aged 56-89 years, clinical dementia rating = 0) underwent serial CSF collection for A beta(1-42), total-tau (t-tau) and phospho-tau(181P) (p-tau). We used preprocessed data from fully automated Roche Elecsys immunoassays. A series of linear regressions were used to examine cross-sectional effects of A beta(1-42), sex, and APOE epsilon 4 on baseline CSF tau and linear mixed models for longitudinal changes in CSF tau. Cross-sectionally, CSF t-tau and p-tau were associated with abnormal A beta(1-42) and APOE epsilon 4 but not with sex. Longitudinally, low baseline CSF A beta(1-42) levels, but not APOE epsilon 4 or sex, predicted faster p-tau accumulation. The relationship between baseline CSF A beta(1-42) and tau accumulation was strongest in APOE epsilon 4 carriers, and particularly female carriers, relative to other groups. The current findings support an association between baseline CSF A beta(1-42) and changes in CSF tau. Elevated risk in females, apparent only in carriers, reinforces findings of sex-related vulnerability in those with genetic predisposition for Alzheimer's disease. (C) 2019 Elsevier Inc. All rights reserved.

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