Evidence map›Paper›PMID 34867294›Full record

ArticleFrontiers in aging neuroscience2021

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

Shannon N Leslie, Jean Kanyo, Dibyadeep Datta, Rashaun S Wilson, Caroline Zeiss, Alvaro Duque, TuKiet T Lam, Amy F T Arnsten, Angus C Nairn

Abstract read
In one paragraph

Article in Frontiers in aging neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Shannon N LeslieDepartment of Psychiatry, Yale School of Medicine, Yale University, New Haven, CT, United States.
Jean KanyoKeck MS & Proteomics Resource, Yale School of Medicine, Yale University, New Haven, CT, United States.
Dibyadeep DattaDepartment of Neuroscience, Yale School of Medicine, Yale University, New Haven, CT, United States.
Rashaun S WilsonKeck MS & Proteomics Resource, Yale School of Medicine, Yale University, New Haven, CT, United States.
Caroline ZeissDepartment of Comparative Medicine, Yale School of Medicine, Yale University, New Haven, CT, United States.
Alvaro DuqueDepartment of Neuroscience, Yale School of Medicine, Yale University, New Haven, CT, United States.
TuKiet T LamKeck MS & Proteomics Resource, Yale School of Medicine, Yale University, New Haven, CT, United States.
Amy F T ArnstenDepartment of Neuroscience, Yale School of Medicine, Yale University, New Haven, CT, United States.
Angus C NairnDepartment of Psychiatry, Yale School of Medicine, Yale University, New Haven, CT, United States.

Funding

Interdepartmental Neuroscience Program (INP)T32NS041228 · NINDS · YALE UNIVERSITY · PI Charles A Greer, Marina R Picciotto · 2001 to 2026
$12.0M
Yale Alzheimer Disease Research CenterP50AG047270 · NIA · YALE UNIVERSITY · PI VAN DYCK, CHRISTOPHER H · 2015 to 2019
$8.3M
Yale Macaque Brain ResourceR01MH113257 · NIMH · YALE UNIVERSITY · PI Alvaro Duque · 2017 to 2026
$4.3M
Preclinical assessment of GCPII inhibitors for cognition and tau pathologyR01AG061190 · NIA · YALE UNIVERSITY · PI ARNSTEN, AMY F.T. · 2019 to 2023
$4.2M
Highly evolved brain circuits in primates: molecular vulnerabilities for diseaseDP1AG047744 · NIA · YALE UNIVERSITY · PI ARNSTEN, AMY F.T. · 2013 to 2017
$4.1M
The Massachusetts and Yale ADRC Collaborative Proteomic Biofluid Biomarker Discovery ProgramR01AG062306 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI ARNOLD, STEVEN E, CARLYLE, BECKY CATHERINE · 2018 to 2022
$3.5M
6500 QTrap Mass Spectrometer for Yale UniversityS10OD018034 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2014 to 2014
$514k
An Ultra-Performance Liquid Chromatography System to Support Metabolomics at Yale UniversityS10OD019967 · OD · YALE UNIVERSITY · PI LAM, TUKIET T · 2015 to 2015
$135k
The Role of cAMP/PKA Dysregulation in Aging and the Initial Stages of Alzheimer'sDiseaseF31AG063425 · NIA · YALE UNIVERSITY · PI LESLIE, SHANNON NOBLE · 2019 to 2020
$55k
NIA NIH HHS DP1 AG047744NIA NIH HHS F31 AG063425NIA NIH HHS P50 AG047270NIA NIH HHS R01 AG061190NIA NIH HHS R01 AG062306NIH HHS S10 OD018034NIH HHS S10 OD019967NIMH NIH HHS R01 MH113257NINDS NIH HHS T32 NS041228
6 · The paper itself

Abstract

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.

Indexed as

agingAlzheimer’s diseasemonkeyphosphoproteomicstau

Identifiers

PMID34867294
PMCPMC8637411

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.