Retinal tau phosphorylation in Alzheimer's disease: A mass spectrometry study
Introduction: Most neurodegenerative diseases, including Alzheimer's disease (AD) and multiple sclerosis (MS), feature abnormal tau phosphorylation (p-tau) in the brain. Prior immunostaining studies have shown p-tau accumulation in the AD retina, suggesting it may mirror brain tau pathology. Me...
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Elsevier
2025-10-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125002736 |
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| author | Jessica Santiago Dovilė Pocevičiūtė Jacob Vogel Gunnar Brinkmalm Malin Wennström |
| author_facet | Jessica Santiago Dovilė Pocevičiūtė Jacob Vogel Gunnar Brinkmalm Malin Wennström |
| author_sort | Jessica Santiago |
| collection | DOAJ |
| description | Introduction: Most neurodegenerative diseases, including Alzheimer's disease (AD) and multiple sclerosis (MS), feature abnormal tau phosphorylation (p-tau) in the brain. Prior immunostaining studies have shown p-tau accumulation in the AD retina, suggesting it may mirror brain tau pathology. Methods: We used mass spectrometry to quantify p-tau peptides in matched retinal and hippocampal samples from non-demented controls (NC, n = 8), AD (n = 12), and MS (n = 4). We compared p-tau levels across diagnoses and analysed correlations between retinal p-tau variants, hippocampal p-tau, and neuropathological changes. Results: Tau peptides phosphorylated at T181, S199/S202, T231, T231 + T235, S396 + T403/S404, and T403/S404 were detected in retinas. Total tau phosphorylation and phosphorylation at S199/S202 and T231 were significantly higher in AD cases compared to NC. These two, along with p-tau S396 + T403/S404, were also higher in cases with high amyloid-beta (Aβ) Braak stages compared to those with low Aβ Braak stages. Higher Aβ stages were also correlated with higher peak intensities of p-tau S199/S202 and S396 + T403/S404, and retinal p-tau S396 + T403/S404 and T403/S404 correlated with neurofibrillary tangle (NFT) Braak stages. Additionally, p-tau S396 + T403/S404 in the retina was associated with corresponding phosphorylation in the hippocampus. Conclusion: Our findings reveal both overlapping and distinct p-tau patterns in retina and hippocampus, with a notable link for p-tau S396 + T403/S404. This enhances our understanding of tauopathies in both tissues and supports retinal tau as a promising biomarker for AD diagnosis and monitoring. |
| format | Article |
| id | doaj-art-315366d75f62473a82cc8839ef7559b4 |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-315366d75f62473a82cc8839ef7559b42025-08-22T04:55:08ZengElsevierNeurobiology of Disease1095-953X2025-10-0121510705710.1016/j.nbd.2025.107057Retinal tau phosphorylation in Alzheimer's disease: A mass spectrometry studyJessica Santiago0Dovilė Pocevičiūtė1Jacob Vogel2Gunnar Brinkmalm3Malin Wennström4Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, SwedenClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, SwedenDepartment of Clinical Sciences Malmö, SciLifeLab, Lund University, Lund, SwedenDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, SwedenClinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden; Corresponding author at: Inga Marie Nilssons gata 53, 214 28 Malmö, Sweden.Introduction: Most neurodegenerative diseases, including Alzheimer's disease (AD) and multiple sclerosis (MS), feature abnormal tau phosphorylation (p-tau) in the brain. Prior immunostaining studies have shown p-tau accumulation in the AD retina, suggesting it may mirror brain tau pathology. Methods: We used mass spectrometry to quantify p-tau peptides in matched retinal and hippocampal samples from non-demented controls (NC, n = 8), AD (n = 12), and MS (n = 4). We compared p-tau levels across diagnoses and analysed correlations between retinal p-tau variants, hippocampal p-tau, and neuropathological changes. Results: Tau peptides phosphorylated at T181, S199/S202, T231, T231 + T235, S396 + T403/S404, and T403/S404 were detected in retinas. Total tau phosphorylation and phosphorylation at S199/S202 and T231 were significantly higher in AD cases compared to NC. These two, along with p-tau S396 + T403/S404, were also higher in cases with high amyloid-beta (Aβ) Braak stages compared to those with low Aβ Braak stages. Higher Aβ stages were also correlated with higher peak intensities of p-tau S199/S202 and S396 + T403/S404, and retinal p-tau S396 + T403/S404 and T403/S404 correlated with neurofibrillary tangle (NFT) Braak stages. Additionally, p-tau S396 + T403/S404 in the retina was associated with corresponding phosphorylation in the hippocampus. Conclusion: Our findings reveal both overlapping and distinct p-tau patterns in retina and hippocampus, with a notable link for p-tau S396 + T403/S404. This enhances our understanding of tauopathies in both tissues and supports retinal tau as a promising biomarker for AD diagnosis and monitoring.http://www.sciencedirect.com/science/article/pii/S0969996125002736RetinaTauP-tauAlzheimer's diseaseMass spectrometry |
| spellingShingle | Jessica Santiago Dovilė Pocevičiūtė Jacob Vogel Gunnar Brinkmalm Malin Wennström Retinal tau phosphorylation in Alzheimer's disease: A mass spectrometry study Neurobiology of Disease Retina Tau P-tau Alzheimer's disease Mass spectrometry |
| title | Retinal tau phosphorylation in Alzheimer's disease: A mass spectrometry study |
| title_full | Retinal tau phosphorylation in Alzheimer's disease: A mass spectrometry study |
| title_fullStr | Retinal tau phosphorylation in Alzheimer's disease: A mass spectrometry study |
| title_full_unstemmed | Retinal tau phosphorylation in Alzheimer's disease: A mass spectrometry study |
| title_short | Retinal tau phosphorylation in Alzheimer's disease: A mass spectrometry study |
| title_sort | retinal tau phosphorylation in alzheimer s disease a mass spectrometry study |
| topic | Retina Tau P-tau Alzheimer's disease Mass spectrometry |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125002736 |
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