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

Author:

Vila‐Castelar Clara1,Chen Yinghua2,Langella Stephanie1,Lopera Francisco3,Zetterberg Henrik45678,Hansson Oskar910,Dage Jeffrey L.11,Janelidzde Shorena9,Su Yi2,Chen Kewei2,Pluim McDowell Celina11213,Martinez Jairo E.112,Ramirez‐Gomez Liliana1,Garcia Gloria3,Aguillon David3,Baena Ana3,Giraldo‐Chica Margarita3,Protas Hillary D.2,Ghisays Valentina2,Rios‐Romenets Silvia3,Tariot Pierre N.2,Blennow Kaj45,Reiman Eric M.2,Quiroz Yakeel T.13

Affiliation:

1. Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA

2. Banner Alzheimer's Institute Phoenix Arizona USA

3. Grupo de Neurociencias de Antioquia, Universidad de Antioquia Medellin Colombia

4. Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg Mölndal Sweden

5. Clinical Neurochemistry Laboratory Sahlgrenska University Hospital Mölndal Sweden

6. Department of Neurodegenerative Disease UCL Institute of Neurology Queen Square London UK

7. UK Dementia Research Institute at UCL London UK

8. Hong Kong Center for Neurodegenerative Diseases Clear Water Bay Hong Kong China

9. Memory Clinic Skåne University Hospital Malmö Sweden

10. Clinical Memory Research Unit Department of Clinical Sciences Malmö Lund University Lund Sweden

11. Indiana University School of Medicine Indianapolis Indiana USA

12. Department of Psychological and Brain Sciences Boston University Boston Massachusetts USA

13. Division of Sleep and Circadian Disorders Department of Medicine Brigham and Women's Hospital, Harvard Medical School Boston Massachusetts USA

Abstract

AbstractINTRODUCTIONPlasma 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.METHODSWe 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.RESULTSAs 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.DISCUSSIONOur 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.

Publisher

Wiley

Subject

Psychiatry and Mental health,Cellular and Molecular Neuroscience,Geriatrics and Gerontology,Neurology (clinical),Developmental Neuroscience,Health Policy,Epidemiology

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