Blood biomarker profiles in young-onset neurocognitive disorders: A cohort study
- Author(s)
- Bhalala, OG; Beamish, J; Eratne, D; Summerell, P; Porter, T; Laws, SM; Kang, MJ; Huq, AJ; Chiu, WH; Cadwallader, C; Walterfang, M; Farrand, S; Evans, AH; Kelso, W; Churilov, L; Watson, R; Yassi, N; Velakoulis, D; Loi, SM;
- Journal Title
- Australian & New Zealand Journal of Psychiatry
- Publication Type
- Jun 17 epub
- Abstract
- INTRODUCTION: Young-onset neurocognitive symptoms result from a heterogeneous group of neurological and psychiatric disorders which present a diagnostic challenge. To identify such factors, we analysed the Biomarkers in Younger-Onset Neurocognitive Disorders cohort, a study of individuals <65 years old presenting with neurocognitive symptoms for a diagnosis and who have undergone cognitive and biomarker analyses. METHODS: Sixty-five participants (median age at assessment of 56 years, 45% female) were recruited during their index presentation to the Royal Melbourne Hospital Neuropsychiatry Centre, a tertiary specialist service in Melbourne, Australia, and categorized as either early-onset Alzheimer's disease (n = 18), non-Alzheimer's disease neurodegeneration (n = 23) or primary psychiatric disorders (n = 24). Levels of neurofilament light chain, glial fibrillary acidic protein and phosphorylated-tau 181, apolipoprotein E genotype and late-onset Alzheimer's disease polygenic risk scores were determined. Information-theoretic model selection identified discriminatory factors. RESULTS: Neurofilament light chain, glial fibrillary acidic protein and phosphorylated-tau 181 levels were elevated in early-onset Alzheimer's disease compared with other diagnostic categories. A multi-omic model selection identified that a combination of cognitive and blood biomarkers, but not the polygenic risk score, discriminated between early-onset Alzheimer's disease and primary psychiatric disorders (area under the curve ⩾ 0.975, 95% confidence interval: 0.825-1.000). Phosphorylated-tau 181 alone significantly discriminated between early-onset Alzheimer's disease and non-Alzheimer's disease neurodegeneration causes (area under the curve = 0.950, 95% confidence interval: 0.877-1.00). DISCUSSION: Discriminating between early-onset Alzheimer's disease, non-Alzheimer's disease neurodegeneration and primary psychiatric disorders causes of young-onset neurocognitive symptoms is possible by combining cognitive profiles with blood biomarkers. These results support utilizing blood biomarkers for the work-up of young-onset neurocognitive symptoms and highlight the need for the development of a young-onset Alzheimer's disease-specific polygenic risk score.
- Publisher
- Sage
- Keywords
- Alzheimer’s disease; Young-onset dementia; apolipoprotein E; glial fibrillary acidic protein; multi-omic analyses; neurodegeneration; neurofilament light; phosphorylated tau 181; polygenic risk scores; primary psychiatric disorder
- Research Division(s)
- Genetics and Gene Regulation
- PubMed ID
- 39825484
- Publisher's Version
- https://doi.org/10.1177/00048674241312805
- Open Access at Publisher's Site
https://doi.org/10.1177/00048674241312805- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-02-07 11:22:03
Last Modified: 2025-02-07 11:24:04