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Retinal tau phosphorylation in Alzheimer's disease : A mass spectrometry study

Santiago, Jessica LU orcid ; Pocevičiūtė, Dovilė LU orcid ; Vogel, Jacob LU ; Brinkmalm, Gunnar and Wennström, Malin LU (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.

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author
; ; ; and
author collaboration
organization
publishing date
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
2025-10-27 22:16:28
@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}},
}