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Journal article
Circulating Metabolite Signatures Associated With Amyloid Positivity, Cognitive Performance and Plasma P-tau181 Levels in Cognitively Unimpaired Older Adults
Molecular neurobiology, Vol.63(1), 892
2026
PMID: 42733048
Abstract
Emerging evidence suggests altered circulating metabolite levels in individuals with Alzheimer's disease (AD) and/or mild cognitive impairment (MCI) compared to healthy controls; how these metabolites alter with early cortical amyloidosis-before symptom onset-remains unclear. This cross-sectional study aimed to investigate plasma metabolites obtained through targeted profiling using the Biocrates AbsoluteIDQ® p400 HR kit. The study cohort comprises 100 cognitively unimpaired (CU) older adults, stratified into CU Aβ- (negative positron emission tomography [PET]-amyloid-beta [Aβ]) and CU Aβ+ (positive PET-Aβ) groups. Significantly altered metabolites were further analysed for associations across amyloid plaque deposition, cognitive performance and plasma tau phosphorylated at threonine 181 (P-tau181) levels and for their ability to differentiate cortical PET-Aβ status in CU older adults. Significant between-group differences were observed in eighteen metabolites from phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and ceramide (Cer) classes, wherein significantly lower levels of PC species and higher levels of LPC(17:1) and Cer(43:1) were detected in CU Aβ+ individuals compared to CU Aβ-. Notably, the differences became more pronounced when PC-to-LPC ratios were analysed. Across the spectrum, lower PC-to-LPC ratios were associated with greater cortical amyloid deposition, poorer cognitive performance and higher plasma P-tau181 levels. Elevated Cer(43:1) levels were also associated with higher cortical amyloid deposition. Upon receiver operating characteristic (ROC) analyses, these metabolite panels significantly distinguished CU Aβ individuals from CU Aβ-, demonstrating good to excellent diagnostic performance. Given their association with membrane damage, synaptic dysfunction, oxidative stress, neuroinflammation and apoptosis, these metabolites may represent potential biomarkers reflecting early AD-related biochemical changes in CU older adults.
Details
- Title
- Circulating Metabolite Signatures Associated With Amyloid Positivity, Cognitive Performance and Plasma P-tau181 Levels in Cognitively Unimpaired Older Adults
- Authors/Creators
- Tahmida Sharmin - University of RajshahiJames D Doecke - Australian e-Health Research CentrePratishtha Chatterjee - Macquarie UniversityHamid R Sohrabi - Murdoch UniversityHenrik Zetterberg - University of GothenburgNicholas J Ashton - University of GothenburgManohar L Garg - Macquarie UniversityKaj Blennow - Sahlgrenska University HospitalRalph N Martins - Edith Cowan University
- Publication Details
- Molecular neurobiology, Vol.63(1), 892
- Publisher
- Springer Nature
- Number of pages
- 20
- Grant note
- 2018- 02532, 681712, 201809- 2016862, 2017- 00915, FO2017-0243 and JPND2019-466-236 / MQ Research Seeding Grant, Macquarie University 101053962 / European Union's Horizon Europe research and innovation programme 2019-02397 / Swedish Research Council
- Identifiers
- 991005917940107891
- Copyright
- © The Author(s) 2026
- Murdoch Affiliation
- School of Psychology; Centre for Healthy Ageing; Health Futures Institute
- Language
- English
- Resource Type
- Journal article
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