Evidence map›Paper›PMID 39655579›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Neuropathology of trisomy 21 mosaicism in a case with early-onset dementia.

Phong T Ngo, Jesse R Pascual, Sierra Wright, Christopher K Williams, Shino Magaki, William H Yong, Harry V Vinters, John M Ringman, Elizabeth Head

Abstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Resistance and resilience to Alzheimer's disease in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  2. Neuropathology of trisomy 21 mosaicism in a case with early-onset dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
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.

Phong T NgoDepartment of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, California, USA.
Jesse R PascualDepartment of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, California, USA.
Sierra WrightDepartment of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, California, USA.
Christopher K WilliamsDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Shino MagakiDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
William H YongDepartment of Pathology and Laboratory Medicine, University of California Medical Center, Irvine, Orange, California, USA.
Harry V VintersDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
John M RingmanDepartment of Neurology, Keck School of Medicine at University of Southern California, Los Angeles, California, USA.
Elizabeth HeadDepartment of Pathology and Laboratory Medicine, University of California, Irvine, Irvine, California, USA.

Funding

Project 3: Biomarkers for DS Clinical TrialsU19AG068054 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEE, JOSEPH HYUNGWOO · 2020 to 2025
$103.7M
The Alzheimer's Disease Research Center at the University of California, IrvineP30AG066519 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Mathew Mark Blurton-Jones · 2020 to 2026
$27.9M
USCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI · 2020 to 2026
$27.8M
National Institutes of Health NIH/NIA U19AG068054NIA NIH HHS P30 AG066519NIA NIH HHS P30AG066519NIA NIH HHS P30 AG066530NIA NIH HHS U19 AG068054
6 · The paper itself

Abstract

introductionThis study investigated the impact of trisomy 21 mosaicism (mT21) on Alzheimer's disease (AD) neuropathology in a well-characterized clinical case described by Ringman et al.

methodsWe describe AD neuropathology in mT21 including amyloid beta, phosphorylated tau, astrogliosis, microgliosis, α-synuclein, and TAR DNA-binding protein 43 (TDP-43) in cerebral cortex, hippocampal subregions, and amygdala using immunohistochemistry.

resultsWe observed high AD neuropathologic change with a score of A3B3C3. In addition, there was widespread astrogliosis, cerebral amyloid angiopathy, and perivascular space widening throughout the brain. Lewy bodies and neurites were noted in the amygdala only and no TDP-43 was observed. DISCUSSION: The findings in this case report highlight that mT21 is sufficient to induce AD neuropathology and early-onset dementia. HIGHLIGHTS: Trisomy 21 mosaicism (mT21) occurs when three copies of chromosome 21 are present in some but not all somatic cells in an individual. mT21 accounts for ≈ 2% of people diagnosed with Down syndrome (DS). Immunohistochemical identification of amyloid beta, tau, astrocytes, microglia, α-synuclein, and TAR DNA-binding protein 43 show that Alzheimer's disease (AD) pathology in mT21 is similar to full trisomy 21. The findings in this case report highlight that mT21 is sufficient to induce AD neuropathology and early-onset dementia.

Indexed as

Alzheimer DiseaseBrainDementiaDown SyndromeMosaicismalpha-SynucleinAmyloid beta-PeptidesDNA-Binding ProteinsHumanstau Proteinsalpha-SynucleinAmyloid beta-PeptidesDNA-Binding ProteinsTARDBP protein, humantau ProteinsAlzheimer's diseaseamyloid betaDown syndromeneurofibrillary tanglesperivascular space widening

Identifiers

PMID39655579
PMCPMC11772706

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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.