An improved immunoassay detects Aβ oligomers in human biofluids: their CSF levels rise with tau and phosphotau levels
Abstract Background Diffusible Aβ oligomers (oAβ) confer cytotoxicity in Alzheimer’s disease. The dynamic complexity of this hydrophobic analyte means few immunoassays exist to quantify oAβ in CSF and plasma. Methods We characterized antibody 71A1 to a cyclized dimer of Aβ9-18 for oAβ preference ove...
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BMC
2025-07-01
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| Series: | Alzheimer’s Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13195-025-01802-x |
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| author | Ting Yang Yi Ran Xu Shanxue Jin Nagendran Ramalingam Jean-Pierre Bellier Alexandra M. Lish Beth L. Ostaszewski Tracy Young-Pearse Lei Liu Hyun-Sik Yang Jasmeer P. Chhatwal Trebor L. Lawton Dennis J. Selkoe |
| author_facet | Ting Yang Yi Ran Xu Shanxue Jin Nagendran Ramalingam Jean-Pierre Bellier Alexandra M. Lish Beth L. Ostaszewski Tracy Young-Pearse Lei Liu Hyun-Sik Yang Jasmeer P. Chhatwal Trebor L. Lawton Dennis J. Selkoe |
| author_sort | Ting Yang |
| collection | DOAJ |
| description | Abstract Background Diffusible Aβ oligomers (oAβ) confer cytotoxicity in Alzheimer’s disease. The dynamic complexity of this hydrophobic analyte means few immunoassays exist to quantify oAβ in CSF and plasma. Methods We characterized antibody 71A1 to a cyclized dimer of Aβ9-18 for oAβ preference over monomers by surface plasmon resonance. We improved an earlier bead-based immunoassay by using 71A1 streptavidin plates for capture and N-terminal antibody 3D6 for detection. Numerous controls systematically validated accuracy. Results 71A1 showed highly selective binding kinetics to Aβ oligomers over monomers. It enriched bioactive oligomers from AD brain that altered neuronal excitatory currents and calcium transients. 71A1/3D6 immunoassay exhibited specificity and reproducibility in human biofluids. CSF oAβ levels correlated positively with CSF tau and phosphorylated-tau-181. APP and PS1 FAD mutations increased oAβ levels in human neuronal media. Conclusions CSF oAβ levels rise in concert with rising tau levels. A new plate-based ELISA offers improved consistency, less sample volume, and lower cost, thus better suited to quantify this challenging analyte. |
| format | Article |
| id | doaj-art-a97c9882b22547e69ae044b5ae6f32e2 |
| institution | Kabale University |
| issn | 1758-9193 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj-art-a97c9882b22547e69ae044b5ae6f32e22025-08-20T04:01:52ZengBMCAlzheimer’s Research & Therapy1758-91932025-07-0117111910.1186/s13195-025-01802-xAn improved immunoassay detects Aβ oligomers in human biofluids: their CSF levels rise with tau and phosphotau levelsTing Yang0Yi Ran Xu1Shanxue Jin2Nagendran Ramalingam3Jean-Pierre Bellier4Alexandra M. Lish5Beth L. Ostaszewski6Tracy Young-Pearse7Lei Liu8Hyun-Sik Yang9Jasmeer P. Chhatwal10Trebor L. Lawton11Dennis J. Selkoe12Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women’s Hospital, Harvard Medical SchoolCenter for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women’s Hospital, Harvard Medical SchoolAbyssinia Biologics, IncDepartment of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical SchoolAbstract Background Diffusible Aβ oligomers (oAβ) confer cytotoxicity in Alzheimer’s disease. The dynamic complexity of this hydrophobic analyte means few immunoassays exist to quantify oAβ in CSF and plasma. Methods We characterized antibody 71A1 to a cyclized dimer of Aβ9-18 for oAβ preference over monomers by surface plasmon resonance. We improved an earlier bead-based immunoassay by using 71A1 streptavidin plates for capture and N-terminal antibody 3D6 for detection. Numerous controls systematically validated accuracy. Results 71A1 showed highly selective binding kinetics to Aβ oligomers over monomers. It enriched bioactive oligomers from AD brain that altered neuronal excitatory currents and calcium transients. 71A1/3D6 immunoassay exhibited specificity and reproducibility in human biofluids. CSF oAβ levels correlated positively with CSF tau and phosphorylated-tau-181. APP and PS1 FAD mutations increased oAβ levels in human neuronal media. Conclusions CSF oAβ levels rise in concert with rising tau levels. A new plate-based ELISA offers improved consistency, less sample volume, and lower cost, thus better suited to quantify this challenging analyte.https://doi.org/10.1186/s13195-025-01802-xAlzheimer’s diseaseBiomarkersAmyloid β-proteinOligomeric AβTauMonitoring |
| spellingShingle | Ting Yang Yi Ran Xu Shanxue Jin Nagendran Ramalingam Jean-Pierre Bellier Alexandra M. Lish Beth L. Ostaszewski Tracy Young-Pearse Lei Liu Hyun-Sik Yang Jasmeer P. Chhatwal Trebor L. Lawton Dennis J. Selkoe An improved immunoassay detects Aβ oligomers in human biofluids: their CSF levels rise with tau and phosphotau levels Alzheimer’s Research & Therapy Alzheimer’s disease Biomarkers Amyloid β-protein Oligomeric Aβ Tau Monitoring |
| title | An improved immunoassay detects Aβ oligomers in human biofluids: their CSF levels rise with tau and phosphotau levels |
| title_full | An improved immunoassay detects Aβ oligomers in human biofluids: their CSF levels rise with tau and phosphotau levels |
| title_fullStr | An improved immunoassay detects Aβ oligomers in human biofluids: their CSF levels rise with tau and phosphotau levels |
| title_full_unstemmed | An improved immunoassay detects Aβ oligomers in human biofluids: their CSF levels rise with tau and phosphotau levels |
| title_short | An improved immunoassay detects Aβ oligomers in human biofluids: their CSF levels rise with tau and phosphotau levels |
| title_sort | improved immunoassay detects aβ oligomers in human biofluids their csf levels rise with tau and phosphotau levels |
| topic | Alzheimer’s disease Biomarkers Amyloid β-protein Oligomeric Aβ Tau Monitoring |
| url | https://doi.org/10.1186/s13195-025-01802-x |
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