Retinal tau phosphorylation in Alzheimer's disease : A mass spectrometry study
(2025) In Neurobiology of Disease 215.- Abstract
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... (More)
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.
(Less)
- author
- Santiago, Jessica
LU
; Pocevičiūtė, Dovilė LU
; Vogel, Jacob LU ; Brinkmalm, Gunnar and Wennström, Malin LU
- author collaboration
- organization
- publishing date
- 2025-10-15
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer's disease, Mass spectrometry, P-tau, Retina, Tau
- in
- Neurobiology of Disease
- volume
- 215
- article number
- 107057
- publisher
- Academic Press
- external identifiers
-
- pmid:40835172
- scopus:105013569593
- ISSN
- 0969-9961
- DOI
- 10.1016/j.nbd.2025.107057
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2025 The Authors
- id
- 28636628-f216-4a2f-864d-50f85810b65e
- date added to LUP
- 2025-09-15 18:03:58
- date last changed
- 2025-09-29 20:03:33
@article{28636628-f216-4a2f-864d-50f85810b65e, abstract = {{<p>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.</p>}}, author = {{Santiago, Jessica and Pocevičiūtė, Dovilė and Vogel, Jacob and Brinkmalm, Gunnar and Wennström, Malin}}, issn = {{0969-9961}}, keywords = {{Alzheimer's disease; Mass spectrometry; P-tau; Retina; Tau}}, language = {{eng}}, month = {{10}}, publisher = {{Academic Press}}, series = {{Neurobiology of Disease}}, title = {{Retinal tau phosphorylation in Alzheimer's disease : A mass spectrometry study}}, url = {{http://dx.doi.org/10.1016/j.nbd.2025.107057}}, doi = {{10.1016/j.nbd.2025.107057}}, volume = {{215}}, year = {{2025}}, }