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

Rachel F Buckley; Elizabeth C Mormino; Jasmeer Chhatwal; Aaron P Schultz; Jennifer S Rabin; Dorene M Rentz; Diler Acar; Michael J Properzi; Julien Dumurgier; Heidi Jacobs; Teresa Gomez-Isla; Keith A Johnson; Reisa A Sperling; Bernard J Hanseeuw; Alzheimer's Disease Neuroimaging Initiative

doi:10.1016/j.neurobiolaging.2019.02.019

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

Neurobiol Aging. 2019 Jun:78:178-185. doi: 10.1016/j.neurobiolaging.2019.02.019. Epub 2019 Mar 7.

Authors

Affiliations

¹ Florey Institutes of Neuroscience and Mental Health, Melbourne, Victoria, Australia; Melbourne School of Psychological Science, University of Melbourne, Victoria, Australia; Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: [email protected].
² Department of Neurology and Neurological Sciences, Stanford University, Santa Clara County, CA, USA.
³ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
⁴ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
⁵ Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
⁶ Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
⁷ Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
⁸ Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA.
⁹ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Massachusetts Alzheimer's Disease Research Center, Boston, MA, USA.
¹⁰ Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA; Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, MA, USA.
¹¹ Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Gordon Center for Medical Imaging, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, USA; Department of Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

PMID: 30947113
PMCID: PMC6545139
DOI: 10.1016/j.neurobiolaging.2019.02.019

Abstract

We investigated the effect of baseline Aβ, 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 Aβ_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 Aβ_1-42, sex, and APOEε4 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 Aβ_1-42 and APOEε4 but not with sex. Longitudinally, low baseline CSF Aβ_1-42 levels, but not APOEε4 or sex, predicted faster p-tau accumulation. The relationship between baseline CSF Aβ_1-42 and tau accumulation was strongest in APOEε4 carriers, and particularly female carriers, relative to other groups. The current findings support an association between baseline CSF Aβ_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.

Keywords: APOE; Alzheimer's disease; Amyloid; Cerebrospinal fluid; Sex; tau.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / genetics
Amyloid beta-Peptides / cerebrospinal fluid*
Apolipoproteins E / genetics*
Cross-Sectional Studies
Female
Genetic Predisposition to Disease / genetics
Healthy Aging / cerebrospinal fluid*
Heterozygote*
Humans
Longitudinal Studies
Male
Middle Aged
Peptide Fragments / cerebrospinal fluid*
Risk
Sex Characteristics*
tau Proteins / cerebrospinal fluid*

Substances

Amyloid beta-Peptides
Apolipoproteins E
Peptide Fragments
amyloid beta-protein (1-42)
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding