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. 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

Rachel F Buckley  1 , Elizabeth C Mormino  2 , Jasmeer Chhatwal  3 , Aaron P Schultz  4 , Jennifer S Rabin  5 , Dorene M Rentz  3 , Diler Acar  6 , Michael J Properzi  7 , Julien Dumurgier  7 , Heidi Jacobs  8 , Teresa Gomez-Isla  9 , Keith A Johnson  10 , Reisa A Sperling  3 , Bernard J Hanseeuw  11 ; Alzheimer's Disease Neuroimaging Initiative
Affiliations
Free PMC article

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

Rachel F Buckley et al. Neurobiol Aging. 2019 Jun.
Free PMC article

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.

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Figures

Figure 1.
Figure 1.. Baseline CSF t-tau and p-tau by (A) sex (B) APOEε4 status and (C) CSF Aβ1–42 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
Figure 2. Longitudinal CSF t-tau and p-tau slopes by baseline CSF Aβ1–42 as stratified by APOEε4 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 Aβ1–42. The colors represent: red = APOEε4 carriers and blue = APOEε4 non-carriers.
Figure 3
Figure 3. Longitudinal CSF t-tau and p-tau accumulation by sex, APOE and baseline CSF Aβ1–42 (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

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