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

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

Author information

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: rfbuckley@mgh.harvard.edu.
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.

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 Aβ1-42, total-tau (t-tau) and phospho-tau181P (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 Aβ1-42, 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 Aβ1-42 and APOEε4 but not with sex. Longitudinally, low baseline CSF Aβ1-42 levels, but not APOEε4 or sex, predicted faster p-tau accumulation. The relationship between baseline CSF Aβ1-42 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 Aβ1-42 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

PMID:
30947113
PMCID:
PMC6545139
[Available on 2020-06-01]
DOI:
10.1016/j.neurobiolaging.2019.02.019
[Indexed for MEDLINE]

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