Saliva Proteome, Metabolome and Microbiome Signatures for Detection of Alzheimer’s Disease
<b>Background:</b> As the burden of Alzheimer’s disease (AD) escalates with an ageing population, the demand for early and accessible diagnostic methods becomes increasingly urgent. Saliva, with its non-invasive and cost-effective nature, presents a promising alternative to cerebrospinal...
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2024-12-01
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| author | Maxime François Dana Pascovici Yanan Wang Toan Vu Jian-Wei Liu David Beale Maryam Hor Jane Hecker Jeff Faunt John Maddison Sally Johns Wayne Leifert |
| author_facet | Maxime François Dana Pascovici Yanan Wang Toan Vu Jian-Wei Liu David Beale Maryam Hor Jane Hecker Jeff Faunt John Maddison Sally Johns Wayne Leifert |
| author_sort | Maxime François |
| collection | DOAJ |
| description | <b>Background:</b> As the burden of Alzheimer’s disease (AD) escalates with an ageing population, the demand for early and accessible diagnostic methods becomes increasingly urgent. Saliva, with its non-invasive and cost-effective nature, presents a promising alternative to cerebrospinal fluid and plasma for biomarker discovery. <b>Methods</b>: In this study, we conducted a comprehensive multi-omics analysis of saliva samples (<i>n</i> = 20 mild cognitive impairment (MCI), <i>n</i> = 20 Alzheimer’s disease and age- and <i>n</i> = 40 gender-matched cognitively normal individuals), from the South Australian Neurodegenerative Disease (SAND) cohort, integrating proteomics, metabolomics, and microbiome data with plasma measurements, including pTau181. <b>Results</b>: Among the most promising findings, the protein Stratifin emerged as a top candidate, showing a strong negative correlation with plasma pTau181 (r = −0.49, <i>p</i> < 0.001) and achieving an AUC of 0.95 in distinguishing AD and MCI combined from controls. In the metabolomics analysis, 3-chlorotyrosine and L-tyrosine exhibited high correlations with disease severity progression, with AUCs of 0.93 and 0.96, respectively. Pathway analysis revealed significant alterations in vitamin B12 metabolism, with Transcobalamin-1 levels decreasing in saliva as AD progressed despite an increase in serum vitamin B12 levels (<i>p</i> = 0.008). Microbiome analysis identified shifts in bacterial composition, with a microbiome cluster containing species such as <i>Lautropia mirabilis</i> showing a significant decrease in abundance in MCI and AD samples. The overall findings were reinforced by weighted correlation network analysis, which identified key hubs and enriched pathways associated with AD. <b>Conclusions</b>: Collectively, these data highlight the potential of saliva as a powerful medium for early AD diagnosis, offering a practical solution for large-scale screening and monitoring. |
| format | Article |
| id | doaj-art-8bdd0d8d89e946e3be28a97d8336509f |
| institution | DOAJ |
| issn | 2218-1989 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj-art-8bdd0d8d89e946e3be28a97d8336509f2025-08-20T02:50:41ZengMDPI AGMetabolites2218-19892024-12-01141271410.3390/metabo14120714Saliva Proteome, Metabolome and Microbiome Signatures for Detection of Alzheimer’s DiseaseMaxime François0Dana Pascovici1Yanan Wang2Toan Vu3Jian-Wei Liu4David Beale5Maryam Hor6Jane Hecker7Jeff Faunt8John Maddison9Sally Johns10Wayne Leifert11Nutrition and Health Program, Molecular Diagnostic Solutions Group, CSIRO Health & Biosecurity, Adelaide, SA 5000, AustraliaCSIRO Health & Biosecurity, Westmead, NSW 2145, AustraliaCSIRO Health & Biosecurity, Microbiomes for One Systems Health-Future Science Platform, Adelaide, SA 5000, AustraliaNutrition and Health Program, Molecular Diagnostic Solutions Group, CSIRO Health & Biosecurity, Adelaide, SA 5000, AustraliaCSIRO Environment, Agricultural and Environmental Sciences Precinct, Acton, Canberra, ACT 2601, AustraliaMetabolomics Unit, CSIRO Environment, Ecosciences Precinct, Dutton Park, QLD 4001, AustraliaNutrition and Health Program, Molecular Diagnostic Solutions Group, CSIRO Health & Biosecurity, Adelaide, SA 5000, AustraliaDepartment of Internal Medicine, Royal Adelaide Hospital, Adelaide, SA 5000, AustraliaDepartment of General Medicine, Royal Adelaide Hospital, Adelaide, SA 5000, AustraliaAged Care Rehabilitation & Palliative Care, SA Health, Modbury Hospital, Modbury, SA 5092, AustraliaAged Care Rehabilitation & Palliative Care, SA Health, Modbury Hospital, Modbury, SA 5092, AustraliaNutrition and Health Program, Molecular Diagnostic Solutions Group, CSIRO Health & Biosecurity, Adelaide, SA 5000, Australia<b>Background:</b> As the burden of Alzheimer’s disease (AD) escalates with an ageing population, the demand for early and accessible diagnostic methods becomes increasingly urgent. Saliva, with its non-invasive and cost-effective nature, presents a promising alternative to cerebrospinal fluid and plasma for biomarker discovery. <b>Methods</b>: In this study, we conducted a comprehensive multi-omics analysis of saliva samples (<i>n</i> = 20 mild cognitive impairment (MCI), <i>n</i> = 20 Alzheimer’s disease and age- and <i>n</i> = 40 gender-matched cognitively normal individuals), from the South Australian Neurodegenerative Disease (SAND) cohort, integrating proteomics, metabolomics, and microbiome data with plasma measurements, including pTau181. <b>Results</b>: Among the most promising findings, the protein Stratifin emerged as a top candidate, showing a strong negative correlation with plasma pTau181 (r = −0.49, <i>p</i> < 0.001) and achieving an AUC of 0.95 in distinguishing AD and MCI combined from controls. In the metabolomics analysis, 3-chlorotyrosine and L-tyrosine exhibited high correlations with disease severity progression, with AUCs of 0.93 and 0.96, respectively. Pathway analysis revealed significant alterations in vitamin B12 metabolism, with Transcobalamin-1 levels decreasing in saliva as AD progressed despite an increase in serum vitamin B12 levels (<i>p</i> = 0.008). Microbiome analysis identified shifts in bacterial composition, with a microbiome cluster containing species such as <i>Lautropia mirabilis</i> showing a significant decrease in abundance in MCI and AD samples. The overall findings were reinforced by weighted correlation network analysis, which identified key hubs and enriched pathways associated with AD. <b>Conclusions</b>: Collectively, these data highlight the potential of saliva as a powerful medium for early AD diagnosis, offering a practical solution for large-scale screening and monitoring.https://www.mdpi.com/2218-1989/14/12/714Alzheimer’s diseasemetabolomicsproteomicssalivamicrobiomesystems biology |
| spellingShingle | Maxime François Dana Pascovici Yanan Wang Toan Vu Jian-Wei Liu David Beale Maryam Hor Jane Hecker Jeff Faunt John Maddison Sally Johns Wayne Leifert Saliva Proteome, Metabolome and Microbiome Signatures for Detection of Alzheimer’s Disease Metabolites Alzheimer’s disease metabolomics proteomics saliva microbiome systems biology |
| title | Saliva Proteome, Metabolome and Microbiome Signatures for Detection of Alzheimer’s Disease |
| title_full | Saliva Proteome, Metabolome and Microbiome Signatures for Detection of Alzheimer’s Disease |
| title_fullStr | Saliva Proteome, Metabolome and Microbiome Signatures for Detection of Alzheimer’s Disease |
| title_full_unstemmed | Saliva Proteome, Metabolome and Microbiome Signatures for Detection of Alzheimer’s Disease |
| title_short | Saliva Proteome, Metabolome and Microbiome Signatures for Detection of Alzheimer’s Disease |
| title_sort | saliva proteome metabolome and microbiome signatures for detection of alzheimer s disease |
| topic | Alzheimer’s disease metabolomics proteomics saliva microbiome systems biology |
| url | https://www.mdpi.com/2218-1989/14/12/714 |
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