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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; Hansson, Oskar; Dage, Jeffrey L; ... Quiroz, Yakeel T; + view all (2023) Sex differences in blood biomarkers and cognitive performance in individuals with autosomal dominant Alzheimer's disease. Alzheimers & Dementia , 19 (9) pp. 4127-4138. 10.1002/alz.13314. Green open access

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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.

Type: Article
Title: Sex differences in blood biomarkers and cognitive performance in individuals with autosomal dominant Alzheimer's disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/alz.13314
Publisher version: https://doi.org/10.1002/alz.13314
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
Keywords: Alzheimer's disease, NfL, P-tau217, autosomal dominant Alzheimer's disease, blood biomarkers, cognition, sex differences
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10175225
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