Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates

Age is the most significant risk factor for Alzheimer’s disease (AD), and understanding its role in specific aspects of AD pathology will be critical for therapeutic development. Neurofibrillary tangles composed of hyperphosphorylated tau are a quintessential hallmark of AD. To study age-related cha...

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Autores principales:	Shannon N. Leslie, Jean Kanyo, Dibyadeep Datta, Rashaun S. Wilson, Caroline Zeiss, Alvaro Duque, TuKiet T. Lam, Amy F. T. Arnsten, Angus C. Nairn
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	tau phosphoproteomics aging monkey Alzheimer’s disease Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/87564d357e044f14867f8f09be13ea2d
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spelling	oai:doaj.org-article:87564d357e044f14867f8f09be13ea2d2021-11-18T09:21:39ZSimple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates1663-436510.3389/fnagi.2021.767322https://doaj.org/article/87564d357e044f14867f8f09be13ea2d2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnagi.2021.767322/fullhttps://doaj.org/toc/1663-4365Age is the most significant risk factor for Alzheimer’s disease (AD), and understanding its role in specific aspects of AD pathology will be critical for therapeutic development. Neurofibrillary tangles composed of hyperphosphorylated tau are a quintessential hallmark of AD. To study age-related changes in tau phosphorylation, we developed a simple, antibody-free approach for single shot analysis of tau phosphorylation across the entire protein by liquid-chromatography tandem mass spectrometry. This methodology is species independent; thus, while initially developed in a rodent model, we utilized this technique to analyze 36 phosphorylation sites on rhesus monkey tau from the prefrontal cortex (PFC), a region vulnerable to AD-linked degeneration. Data are available via ProteomeXchange with identifier PXD027971. We identified novel, age-related changes in tau phosphorylation in the rhesus monkey PFC and analyzed patterns of phosphorylation change across domains of the protein. We confirmed a significant increase and positive correlation with age of phosphorylated serine 235 tau and phosphorylated serine 396 tau levels in an expanded cohort of 14 monkeys. Histology showed robust labeling for tau phosphorylated at these sites in vulnerable layer III pyramidal cells in the PFC. The results presented in this study suggest an important role of the natural aging process in tau phosphorylation in rhesus monkey.Shannon N. LeslieShannon N. LeslieJean KanyoDibyadeep DattaRashaun S. WilsonCaroline ZeissAlvaro DuqueTuKiet T. LamTuKiet T. LamAmy F. T. ArnstenAngus C. NairnFrontiers Media S.A.articletauphosphoproteomicsagingmonkeyAlzheimer’s diseaseNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Aging Neuroscience, Vol 13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tau phosphoproteomics aging monkey Alzheimer’s disease Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	tau phosphoproteomics aging monkey Alzheimer’s disease Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Shannon N. Leslie Shannon N. Leslie Jean Kanyo Dibyadeep Datta Rashaun S. Wilson Caroline Zeiss Alvaro Duque TuKiet T. Lam TuKiet T. Lam Amy F. T. Arnsten Angus C. Nairn Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates
description	Age is the most significant risk factor for Alzheimer’s disease (AD), and understanding its role in specific aspects of AD pathology will be critical for therapeutic development. Neurofibrillary tangles composed of hyperphosphorylated tau are a quintessential hallmark of AD. To study age-related changes in tau phosphorylation, we developed a simple, antibody-free approach for single shot analysis of tau phosphorylation across the entire protein by liquid-chromatography tandem mass spectrometry. This methodology is species independent; thus, while initially developed in a rodent model, we utilized this technique to analyze 36 phosphorylation sites on rhesus monkey tau from the prefrontal cortex (PFC), a region vulnerable to AD-linked degeneration. Data are available via ProteomeXchange with identifier PXD027971. We identified novel, age-related changes in tau phosphorylation in the rhesus monkey PFC and analyzed patterns of phosphorylation change across domains of the protein. We confirmed a significant increase and positive correlation with age of phosphorylated serine 235 tau and phosphorylated serine 396 tau levels in an expanded cohort of 14 monkeys. Histology showed robust labeling for tau phosphorylated at these sites in vulnerable layer III pyramidal cells in the PFC. The results presented in this study suggest an important role of the natural aging process in tau phosphorylation in rhesus monkey.
format	article
author	Shannon N. Leslie Shannon N. Leslie Jean Kanyo Dibyadeep Datta Rashaun S. Wilson Caroline Zeiss Alvaro Duque TuKiet T. Lam TuKiet T. Lam Amy F. T. Arnsten Angus C. Nairn
author_facet	Shannon N. Leslie Shannon N. Leslie Jean Kanyo Dibyadeep Datta Rashaun S. Wilson Caroline Zeiss Alvaro Duque TuKiet T. Lam TuKiet T. Lam Amy F. T. Arnsten Angus C. Nairn
author_sort	Shannon N. Leslie
title	Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates
title_short	Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates
title_full	Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates
title_fullStr	Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates
title_full_unstemmed	Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates
title_sort	simple, single-shot phosphoproteomic analysis of heat-stable tau identifies age-related changes in ps235- and ps396-tau levels in non-human primates
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/87564d357e044f14867f8f09be13ea2d
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Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates

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