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

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...

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Published inAlzheimer's & dementia Vol. 19; no. 9; pp. 4127 - 4138
Main Authors Vila‐Castelar, Clara, Chen, Yinghua, Langella, Stephanie, Lopera, Francisco, Zetterberg, Henrik, Hansson, Oskar, Dage, Jeffrey L., Janelidzde, Shorena, Su, Yi, Chen, Kewei, Pluim McDowell, Celina, Martinez, Jairo E., Ramirez‐Gomez, Liliana, Garcia, Gloria, Aguillon, David, Baena, Ana, Giraldo‐Chica, Margarita, Protas, Hillary D., Ghisays, Valentina, Rios‐Romenets, Silvia, Tariot, Pierre N., Blennow, Kaj, Reiman, Eric M., Quiroz, Yakeel T.
Format Journal Article
LanguageEnglish
Published United States 01.09.2023
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Summary: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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ISSN:1552-5260
1552-5279
1552-5279
DOI:10.1002/alz.13314