Uncovering elevated tau TPP motif phosphorylation in the brain of Alzheimer's disease patients
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association..
INTRODUCTION: A wide array of post-translational modifications of the tau protein occurs in Alzheimer's disease (AD) and they are critical to pathogenesis and biomarker development. Several promising tau markers, pT181, pT217, and pT231, rely on increased phosphorylation within a common molecular motif threonine-proline-proline (TPP).
METHODS: We validated new and existing antibodies against pT217, pT231, pT175, and pT181, then combined immunohistochemistry (IHC) and immunoassays (ELISA) to broadly examine the phosphorylation of the tau TPP motif in AD brains.
RESULTS: The tau burden, as examined by IHC and ELISA, correlates to Braak stages across all TPP sites. Moreover, we observed regional variability across four TPP motif phosphorylation sites in multiple brains of sporadic AD patients.
DISCUSSION: We conclude that there is an elevation of TPP tau phosphorylation in AD brains as disease advances. The regional variability of pTPP tau suggests that examining different phosphorylation sites is essential for a comprehensive assessment of tau pathology.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Alzheimer's & dementia : the journal of the Alzheimer's Association - 20(2024), 3 vom: 03. März, Seite 1573-1585 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bellier, Jean-Pierre [VerfasserIn] |
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| Links: |
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| Themen: |
2ZD004190S |
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| Anmerkungen: |
Date Completed 18.03.2024 Date Revised 03.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/alz.13557 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Bellier, Jean-Pierre |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Uncovering elevated tau TPP motif phosphorylation in the brain of Alzheimer's disease patients |
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| 500 | |a Date Revised 03.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. | ||
| 520 | |a INTRODUCTION: A wide array of post-translational modifications of the tau protein occurs in Alzheimer's disease (AD) and they are critical to pathogenesis and biomarker development. Several promising tau markers, pT181, pT217, and pT231, rely on increased phosphorylation within a common molecular motif threonine-proline-proline (TPP) | ||
| 520 | |a METHODS: We validated new and existing antibodies against pT217, pT231, pT175, and pT181, then combined immunohistochemistry (IHC) and immunoassays (ELISA) to broadly examine the phosphorylation of the tau TPP motif in AD brains | ||
| 520 | |a RESULTS: The tau burden, as examined by IHC and ELISA, correlates to Braak stages across all TPP sites. Moreover, we observed regional variability across four TPP motif phosphorylation sites in multiple brains of sporadic AD patients | ||
| 520 | |a DISCUSSION: We conclude that there is an elevation of TPP tau phosphorylation in AD brains as disease advances. The regional variability of pTPP tau suggests that examining different phosphorylation sites is essential for a comprehensive assessment of tau pathology | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Cai, Yuqi |e verfasserin |4 aut | |
| 700 | 1 | |a Alam, Sarah M |e verfasserin |4 aut | |
| 700 | 1 | |a Wiederhold, Thorsten |e verfasserin |4 aut | |
| 700 | 1 | |a Aiello, Arica |e verfasserin |4 aut | |
| 700 | 1 | |a Vogelgsang, Jonathan S |e verfasserin |4 aut | |
| 700 | 1 | |a Berretta, Sabina |e verfasserin |4 aut | |
| 700 | 1 | |a Chhatwal, Jasmeer P |e verfasserin |4 aut | |
| 700 | 1 | |a Selkoe, Dennis J |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Lei |e verfasserin |4 aut | |
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