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. 2023 Sep;19(9):4127-4138.
doi: 10.1002/alz.13314. Epub 2023 Jun 6.

Sex differences in blood biomarkers and cognitive performance in individuals with autosomal dominant Alzheimer's disease

Clara Vila-Castelar  1 , Yinghua Chen  2 , Stephanie Langella  1 , Francisco Lopera  3 , Henrik Zetterberg  4   5   6   7   8 , Oskar Hansson  9   10 , Jeffrey L Dage  11 , Shorena Janelidzde  9 , Yi Su  2 , Kewei Chen  2 , Celina Pluim McDowell  1   12   13 , Jairo E Martinez  1   12 , Liliana Ramirez-Gomez  1 , Gloria Garcia  3 , David Aguillon  3 , Ana Baena  3 , Margarita Giraldo-Chica  3 , Hillary D Protas  2 , Valentina Ghisays  2 , Silvia Rios-Romenets  3 , Pierre N Tariot  2 , Kaj Blennow  4   5 , Eric M Reiman  2 , Yakeel T Quiroz  1   3
Affiliations

Sex differences in blood biomarkers and cognitive performance in individuals with autosomal dominant Alzheimer's disease

Clara Vila-Castelar et al. Alzheimers Dement. 2023 Sep.

Abstract

Introduction: Plasma tau phosphorylated at threonine 217 (P-tau217) and neurofilament light (NfL) have emerged as markers of Alzheimer's disease (AD) pathology. Few studies have examined the role of sex in plasma biomarkers in sporadic AD, yielding mixed findings, and none in autosomal dominant AD.

Methods: We examined the effects of sex and age on plasma P-tau217 and NfL, and their association with cognitive performance in a cross-sectional study of 621 Presenilin-1 E280A mutation carriers (PSEN1) and non-carriers.

Results: As plasma P-tau217 levels increase, cognitively unimpaired female carriers showed better cognitive performance than cognitively unimpaired male carriers. Yet, as disease progresses, female carriers had a greater plasma NfL increase than male carriers. There were no sex differences in the association between age and plasma biomarkers among non-carriers.

Discussion: Our findings suggest that, among PSEN1 mutation carriers, females had a greater rate of neurodegeneration than males, yet it did not predict cognitive performance.

Highlights: We examined sex differences in plasma P-tau217 and NfL in Presenilin-1 E280A (PSEN1) mutation carriers and non-carriers. Female carriers had a greater plasma NfL increase, but not P-tau217, than male carriers. As plasma P-tau217 levels increase, cognitively unimpaired female carriers showed better cognitive performance than cognitively unimpaired male carriers. The interaction effect of sex by plasma NfL levels did not predict cognition among carriers.

Keywords: Alzheimer's disease; NfL; P-tau217; autosomal dominant Alzheimer's disease; blood biomarkers; cognition; sex differences.

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Figures

Figure 1.
Figure 1.. Age trajectories of plasma P-tau217 and NfL in male and female PSEN1 mutation carriers.
(A) Log10 Plasma P-tau217 as a function of age. (B) LOESS plot of Log10 Plasma P-tau217 as a function of age. (C) Log10 Plasma NfL as a function of age. (D) LOESS plot of Log10 Plasma NfL as a function of age. Dashed line represents the age at which male and female carriers LOESS fit confidence band separate (age of 48.45). Abbreviations: NfL, Neurofilament light chain; P-tau217, Plasma-measured tau phosphorylated at threonine 217. Orange represents female carriers and green represents male carriers.
Figure 2.
Figure 2.. Associations between plasma P-tau217 and NfL and cognitive performance in male and female PSEN1 mutation carriers.
(A) CERAD word list delayed recall as a function of Log10 Plasma P-tau217. (B) API cognitive composite score as a function of Log10 Plasma P-tau217. (C) CERAD word list delayed recall as a function of Log10 Plasma NfL. (D) API cognitive composite score as a function of Log10 Plasma NfL. Abbreviations: NfL, Neurofilament light chain; P-tau217, Plasma-measured tau phosphorylated at threonine 217; CERAD, Consortium to Establish a Registry for Alzheimer’s Disease; API, Alzheimer Prevention Initiative. Orange represents female carriers, and green represents male carriers. Circles represent cognitively unimpaired carriers, and triangles represent cognitively impaired carriers.
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