Neurobiology of disease · 2025
Retinal tau phosphorylation in Alzheimer's disease: A mass spectrometry study.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Santiago Jessica, Pocevičiūtė Dovilė, Vogel Jacob, Netherlands Brain Bank, Brinkmalm Gunnar, Wennström Malin
Аннотация
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.
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.