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

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: 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.

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

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

Rachel F Buckley et al. Neurobiol Aging. 2019 Jun.

. 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: 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.

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.

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Figures

**Figure 1.. Baseline CSF t-tau and p-tau by (A) sex (B) *APOE*ε4 status and (C) CSF Aβ_1–42 status**
The x-axis represents CSF t-tau or p-tau pg/mL at baseline. Each violin plot represents the density of the data at each level of pg/mL, with a boxplot overlaid to indicate the median level for each group.

**Figure 2. Longitudinal CSF t-tau and p-tau slopes by baseline CSF Aβ_1–42 as stratified by *APOE*ε4 status**
The y-axis represents slopes of CSF tau change in pg/mL per year (extracted from linear mixed models), while the x-axis represents baseline CSF Aβ_1–42. The colors represent: red = *APOE*ε4 carriers and blue = *APOE*ε4 non-carriers.

**Figure 3. Longitudinal CSF t-tau and p-tau accumulation by sex, *APOE* and baseline CSF Aβ_1–42 (depicted here as a dichotomous variable)**
The y-axis represents CSF tau pg/mL while the x-axis represents time in the study (in years). The colors represent: purple = male Aβ−, green = male Aβ+, blue = female Aβ−, red = female Aβ+.

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous