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

Vila-Castelar, Clara ; Chen, Yinghua ; Langella, Stephanie ; Lopera, Francisco ; Zetterberg, Henrik LU ; Hansson, Oskar LU orcid ; Dage, Jeffrey L. ; Janelidzde, Shorena ; Su, Yi and Chen, Kewei , et al. (2023) In Alzheimer's and Dementia 19(9). p.4127-4138
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, autosomal dominant Alzheimer's disease, blood biomarkers, cognition, NfL, P-tau217, sex differences
in
Alzheimer's and Dementia
volume
19
issue
9
pages
4127 - 4138
publisher
Wiley
external identifiers
  • scopus:85161474660
  • pmid:37279390
ISSN
1552-5260
DOI
10.1002/alz.13314
language
English
LU publication?
yes
id
0429de36-33c8-442e-93f8-a14a13ceb13a
date added to LUP
2023-08-23 11:33:24
date last changed
2024-12-16 01:55:04
@article{0429de36-33c8-442e-93f8-a14a13ceb13a,
  abstract     = {{<p>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.</p>}},
  author       = {{Vila-Castelar, Clara and Chen, Yinghua and Langella, Stephanie and Lopera, Francisco and Zetterberg, Henrik and Hansson, Oskar and Dage, Jeffrey L. and Janelidzde, Shorena and Su, Yi and Chen, Kewei and Pluim McDowell, Celina and Martinez, Jairo E. and Ramirez-Gomez, Liliana and Garcia, Gloria and Aguillon, David and Baena, Ana and Giraldo-Chica, Margarita and Protas, Hillary D. and Ghisays, Valentina and Rios-Romenets, Silvia and Tariot, Pierre N. and Blennow, Kaj and Reiman, Eric M. and Quiroz, Yakeel T.}},
  issn         = {{1552-5260}},
  keywords     = {{Alzheimer's disease; autosomal dominant Alzheimer's disease; blood biomarkers; cognition; NfL; P-tau217; sex differences}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{4127--4138}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{Sex differences in blood biomarkers and cognitive performance in individuals with autosomal dominant Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1002/alz.13314}},
  doi          = {{10.1002/alz.13314}},
  volume       = {{19}},
  year         = {{2023}},
}