Evidence map›Paper›PMID 33709107›Full record

ArticleJournal of neuropathology and experimental neurology2021

Pontine Arteriolosclerosis and Locus Coeruleus Oxidative Stress Differentiate Resilience from Mild Cognitive Impairment in a Clinical Pathologic Cohort.

Sarah C Kelly, Peter T Nelson, Scott E Counts

Open access · bronzeAbstract read
In one paragraph

Article in Journal of neuropathology and experimental neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.7field-weighted citation impact, top 17% of its field
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

11 citing papers in PubMed, 16 citations in OpenAlex.

  1. Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  2. Age-Related Increase in Locus Ceruleus Activity and Connectivity with the Prefrontal Cortex during Ambiguity Processing.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Locus coeruleus pathology is associated with cerebral microangiopathy at autopsy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023
    Article
  10. Review
  11. Review
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

3 authors at 3 institutions in 1 country.

Sarah C KellyFrom the Department of Translational Neuroscience, Michigan State University, Grand Rapids, Michigan.
Peter T NelsonDepartment of Pathology and Laboratory Medicine, University of Kentucky, Lexington, Kentucky.
Scott E CountsFrom the Department of Translational Neuroscience, Michigan State University, Grand Rapids, Michigan.
Michigan Cancer Research Consortium · USMichigan State University · USUniversity of Kentucky · US

Funding

TAU, AB, SYNUCLEIN AND NITRATIVE/OXIDATIVE DAMAGE IN MCIP01AG014449 · NIA · UNIVERSITY OF PITTSBURGH · PI COUNTS, SCOTT E · 1997 to 2024
$39.7M
University of Kentucky Alzheimer's Disease Research CenterP30AG072946 · NIA · UNIVERSITY OF KENTUCKY · PI LINDA J VAN ELDIK · 2021 to 2026
$23.5M
University of Kentucky Alzheimer's Disease Core Center - Biomarker CoreP30AG028383 · NIA · UNIVERSITY OF KENTUCKY · PI GOLD, BRIAN TIMOTHY, VAN ELDIK, LINDA J · 2006 to 2020
$23.3M
Michigan Alzheimer's Disease Core CenterP30AG053760 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALBIN, ROGER L · 2016 to 2020
$10.1M
Central noradrenergic mechanisms of cerebrovascular pathology in Alzheimer's diseaseR01AG060731 · NIA · MICHIGAN STATE UNIVERSITY · PI COUNTS, SCOTT E · 2019 to 2023
$2.4M
NIA NIH HHS P01 AG014449NIA NIH HHS P30 AG028383NIA NIH HHS P30 AG053760NIA NIH HHS P30 AG072946NIA NIH HHS R01 AG060731
6 · The paper itself

Abstract

Locus coeruleus (LC) neurodegeneration is associated with cognitive deterioration during the transition from normal cognition to mild cognitive impairment (MCI) and Alzheimer disease (AD). However, the extent to which LC degenerative processes differentiate cognitively normal, "resilient" subjects bearing a high AD pathological burden from those with MCI or AD remains unclear. We approached this problem by quantifying the number of LC neurons and the percentage of LC neurons bearing AT8 tau pathology, TDP-43 pathology, or a marker for DNA/RNA oxidative damage, in well-characterized subjects diagnosed as normal cognition-low AD pathology (NC-LP), NC-high AD pathology (NC-HP), MCI, or mild/moderate AD. In addition, the severity of pontine arteriolosclerosis in each subject was compared across the groups. There was a trend for a step-wise ∼20% loss of LC neuron number between the NC-LP, NC-HP and MCI subjects despite a successive, significant ∼80%-100% increase in tau pathology between these groups. In contrast, increasing pontine arteriolosclerosis severity scores and LC oxidative stress burden significantly separated the NC-LP/HP and MCI/AD groups via comparative, correlation, and regression analysis. Pontine perfusion, as well as LC neuronal metabolic and redox function, may impact noradrenergic LC modulation of cognition during the preclinical and prodromal stages of AD.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseArteriolosclerosisBrief Psychiatric Rating ScaleCognitive DysfunctionCohort StudiesDiagnosis, DifferentialFemaleHumansLocus CoeruleusMaleOxidative StressPonsResilience, PsychologicalAlzheimer diseaseArteriolosclerosisLocus coeruleusMild cognitive impairmentOxidative stressPonsResilience

Identifiers

PMID33709107
PMCPMC7985827
OpenAlexW3133902980

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.