Serum metabolic signatures for Alzheimer’s Disease reveal alterations in amino acid composition: a validation study
<h3>Introduction</h3><p dir="ltr">Alzheimer’s Disease (AD) is complex and novel approaches are urgently needed to aid in diagnosis. Blood is frequently used as a source for biomarkers; however, its complexity prevents proper detection. The analytical power of metabolomics...
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| مؤلفون آخرون: | , , , , , , |
| منشور في: |
2024
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| _version_ | 1864513545569304576 |
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| author | Jonas Ellegaard Nielsen (21633062) |
| author2 | Trygve Andreassen (7373192) Charlotte Held Gotfredsen (8350599) Dorte Aalund Olsen (9191732) Karsten Vestergaard (17016778) Jonna Skov Madsen (5238674) Søren Risom Kristensen (2792272) Shona Pedersen (2792278) |
| author2_role | author author author author author author author |
| author_facet | Jonas Ellegaard Nielsen (21633062) Trygve Andreassen (7373192) Charlotte Held Gotfredsen (8350599) Dorte Aalund Olsen (9191732) Karsten Vestergaard (17016778) Jonna Skov Madsen (5238674) Søren Risom Kristensen (2792272) Shona Pedersen (2792278) |
| author_role | author |
| dc.creator.none.fl_str_mv | Jonas Ellegaard Nielsen (21633062) Trygve Andreassen (7373192) Charlotte Held Gotfredsen (8350599) Dorte Aalund Olsen (9191732) Karsten Vestergaard (17016778) Jonna Skov Madsen (5238674) Søren Risom Kristensen (2792272) Shona Pedersen (2792278) |
| dc.date.none.fl_str_mv | 2024-01-05T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1007/s11306-023-02078-8 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Serum_metabolic_signatures_for_Alzheimer_s_Disease_reveal_alterations_in_amino_acid_composition_a_validation_study/29445593 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Medical biochemistry and metabolomics Neurosciences Alzheimer Metabolites Biomarker Serum Nuclear magnetic resonance Single molecule array |
| dc.title.none.fl_str_mv | Serum metabolic signatures for Alzheimer’s Disease reveal alterations in amino acid composition: a validation study |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3>Introduction</h3><p dir="ltr">Alzheimer’s Disease (AD) is complex and novel approaches are urgently needed to aid in diagnosis. Blood is frequently used as a source for biomarkers; however, its complexity prevents proper detection. The analytical power of metabolomics, coupled with statistical tools, can assist in reducing this complexity.</p><h3>Objectives</h3><p dir="ltr">Thus, we sought to validate a previously proposed panel of metabolic blood-based biomarkers for AD and expand our understanding of the pathological mechanisms involved in AD that are reflected in the blood.</p><h3>Methods</h3><p dir="ltr">In the validation cohort serum and plasma were collected from 25 AD patients and 25 healthy controls. Serum was analysed for metabolites using nuclear magnetic resonance (NMR) spectroscopy, while plasma was tested for markers of neuronal damage and AD hallmark proteins using single molecule array (SIMOA).</p><h3>Results</h3><p dir="ltr">The diagnostic performance of the metabolite biomarker panel was confirmed using sparse-partial least squares discriminant analysis (sPLS-DA) with an area under the curve (AUC) of 0.73 (95% confidence interval: 0.59–0.87). Pyruvic acid and valine were consistently reduced in the discovery and validation cohorts. Pathway analysis of significantly altered metabolites in the validation set revealed that they are involved in branched-chain amino acids (BCAAs) and energy metabolism (glycolysis and gluconeogenesis). Additionally, strong positive correlations were observed for valine and isoleucine between cerebrospinal fluid p-tau and t-tau.</p><h3>Conclusions</h3><p dir="ltr">Our proposed panel of metabolites was successfully validated using a combined approach of NMR and sPLS-DA. It was discovered that cognitive-impairment-related metabolites belong to BCAAs and are involved in energy metabolism.</p><h2>Other Information</h2><p dir="ltr">Published in: Metabolomics<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s11306-023-02078-8" target="_blank">https://dx.doi.org/10.1007/s11306-023-02078-8</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_85fb86c0ae41a13a714ea8d8c76174e3 |
| identifier_str_mv | 10.1007/s11306-023-02078-8 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/29445593 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Serum metabolic signatures for Alzheimer’s Disease reveal alterations in amino acid composition: a validation studyJonas Ellegaard Nielsen (21633062)Trygve Andreassen (7373192)Charlotte Held Gotfredsen (8350599)Dorte Aalund Olsen (9191732)Karsten Vestergaard (17016778)Jonna Skov Madsen (5238674)Søren Risom Kristensen (2792272)Shona Pedersen (2792278)Biomedical and clinical sciencesMedical biochemistry and metabolomicsNeurosciencesAlzheimerMetabolitesBiomarkerSerumNuclear magnetic resonanceSingle molecule array<h3>Introduction</h3><p dir="ltr">Alzheimer’s Disease (AD) is complex and novel approaches are urgently needed to aid in diagnosis. Blood is frequently used as a source for biomarkers; however, its complexity prevents proper detection. The analytical power of metabolomics, coupled with statistical tools, can assist in reducing this complexity.</p><h3>Objectives</h3><p dir="ltr">Thus, we sought to validate a previously proposed panel of metabolic blood-based biomarkers for AD and expand our understanding of the pathological mechanisms involved in AD that are reflected in the blood.</p><h3>Methods</h3><p dir="ltr">In the validation cohort serum and plasma were collected from 25 AD patients and 25 healthy controls. Serum was analysed for metabolites using nuclear magnetic resonance (NMR) spectroscopy, while plasma was tested for markers of neuronal damage and AD hallmark proteins using single molecule array (SIMOA).</p><h3>Results</h3><p dir="ltr">The diagnostic performance of the metabolite biomarker panel was confirmed using sparse-partial least squares discriminant analysis (sPLS-DA) with an area under the curve (AUC) of 0.73 (95% confidence interval: 0.59–0.87). Pyruvic acid and valine were consistently reduced in the discovery and validation cohorts. Pathway analysis of significantly altered metabolites in the validation set revealed that they are involved in branched-chain amino acids (BCAAs) and energy metabolism (glycolysis and gluconeogenesis). Additionally, strong positive correlations were observed for valine and isoleucine between cerebrospinal fluid p-tau and t-tau.</p><h3>Conclusions</h3><p dir="ltr">Our proposed panel of metabolites was successfully validated using a combined approach of NMR and sPLS-DA. It was discovered that cognitive-impairment-related metabolites belong to BCAAs and are involved in energy metabolism.</p><h2>Other Information</h2><p dir="ltr">Published in: Metabolomics<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1007/s11306-023-02078-8" target="_blank">https://dx.doi.org/10.1007/s11306-023-02078-8</a></p>2024-01-05T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s11306-023-02078-8https://figshare.com/articles/journal_contribution/Serum_metabolic_signatures_for_Alzheimer_s_Disease_reveal_alterations_in_amino_acid_composition_a_validation_study/29445593CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/294455932024-01-05T03:00:00Z |
| spellingShingle | Serum metabolic signatures for Alzheimer’s Disease reveal alterations in amino acid composition: a validation study Jonas Ellegaard Nielsen (21633062) Biomedical and clinical sciences Medical biochemistry and metabolomics Neurosciences Alzheimer Metabolites Biomarker Serum Nuclear magnetic resonance Single molecule array |
| status_str | publishedVersion |
| title | Serum metabolic signatures for Alzheimer’s Disease reveal alterations in amino acid composition: a validation study |
| title_full | Serum metabolic signatures for Alzheimer’s Disease reveal alterations in amino acid composition: a validation study |
| title_fullStr | Serum metabolic signatures for Alzheimer’s Disease reveal alterations in amino acid composition: a validation study |
| title_full_unstemmed | Serum metabolic signatures for Alzheimer’s Disease reveal alterations in amino acid composition: a validation study |
| title_short | Serum metabolic signatures for Alzheimer’s Disease reveal alterations in amino acid composition: a validation study |
| title_sort | Serum metabolic signatures for Alzheimer’s Disease reveal alterations in amino acid composition: a validation study |
| topic | Biomedical and clinical sciences Medical biochemistry and metabolomics Neurosciences Alzheimer Metabolites Biomarker Serum Nuclear magnetic resonance Single molecule array |