Logo image
Back
Circulating medium‐ and long‐chain acylcarnitines are associated with plasma P‐tau181 in cognitively normal older adults
Journal article   Open access   Peer reviewed

Circulating medium‐ and long‐chain acylcarnitines are associated with plasma P‐tau181 in cognitively normal older adults

Tahmida Sharmin, Pratishtha Chatterjee, James D. Doecke, Nicholas J. Ashton, Kevin Huynh, Steve Pedrini, Hamid R. Sohrabi, Benjamin Heng, Shaun Eslick, Henrik Zetterberg, …
Journal of neurochemistry, Vol.169(2)
2024
DOI: https://doi.org/10.1111/jnc.16244
PMID: 39473263
pdf
Published4.54 MBDownloadView
CC BY V4.0,  Open Access

Abstract

acylcarnitines Alzheimer's disease biomarkers cognitively normal older adults initial pathogenesis P-tau181
Alzheimer's disease (AD) pathogenesis involves dysregulation in diverse biochemical processes. Nevertheless, plasma tau phosphorylated at threonine 181 (P‐tau181), a recognised AD biomarker, has been described to reflect early‐stage cortical amyloid‐β (Aβ) deposition in cognitively normal (CN) adults. Therefore, identifying changes in plasma metabolites associated with plasma P‐tau181 at the pre‐clinical stage may provide insights into underlying biochemical mechanisms to better understand initial AD pathogenesis. In the current study, plasma P‐tau181, quantified via single molecule array (Simoa) technology, and plasma metabolites, quantified via targeted‐mass spectrometry, were investigated for associations in CN older adults and upon stratification by positron emission tomography (PET)‐Aβ load. In addition, the P‐tau181‐linked metabolites were evaluated for cognitive performance and neuroimaging markers of AD and the potential to distinguish between CN Aβ− and CN Aβ+ individuals. Significant positive associations of medium‐ and long‐chain acylcarnitines (ACs) were observed with P‐tau181 in the entire cohort, CN Aβ− and CN Aβ+, suggesting a link between initial Aβ pathology and fatty acid oxidation‐mediated energy metabolism pathways. However, in CN Aβ−, additional linear associations of P‐tau181 were observed with muscle metabolism and nitric oxide homeostasis‐associated metabolites. Upon investigating the P‐tau181‐linked metabolites for cognitive performance, significant inverse correlations of the verbal and visual episodic memory and the global composite score were noted in CN Aβ+ with medium‐ and long‐chain ACs, suggesting prognostic value of ACs accompanying weaker cognitive performance. While investigating neuroimaging markers, ACs had positive associations with PET‐Aβ load and inverse associations with hippocampal volume in CN Aβ+, indicating connections of ACs with initial AD pathogenesis. Furthermore, based on receiver operating characteristics analysis, the associated ACs potentially classified PET‐Aβ status in older adults. Therefore, plasma P‐tau181‐linked circulating ACs may serve as potential prognostic markers for initial AD pathogenesis in CN older adults. However, further cross‐sectional and longitudinal research in highly characterised AD cohorts is needed to validate current findings. image

Details

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

Metrics

2 File views/ downloads
22 Record Views
2 Times Cited - Web of Science

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types
Domestic collaboration
International collaboration
Citation topics
1 Clinical & Life Sciences
1.52 Neurodegenerative Diseases
1.52.60 Dementia
Web Of Science research areas
Biochemistry & Molecular Biology
Neurosciences
ESI research areas
Neuroscience & Behavior
Logo image