Evidence map›Paper›PMID 39265450›Full record

ArticleNeurobiology of aging2024

Maternal choline supplementation rescues early endosome pathology in basal forebrain cholinergic neurons in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease.

Megan K Gautier, Christy M Kelley, Sang Han Lee, Elliott J Mufson, Stephen D Ginsberg

Abstract read
In one paragraph

Article in Neurobiology of aging, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
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  8. 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

5 authors.

Megan K GautierCenter for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA; Pathobiology and Translational Medicine Program, New York University Grossman School of Medicine, New York, NY, USA; NYU Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA.
Christy M KelleyComplex Adaptive Systems Initiative, Arizona State University, Tempe, AZ, USA; Institute for Future Health, Scottsdale, AZ, USA.
Sang Han LeeCenter for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA; Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA.
Elliott J MufsonDepartments of Translational Neuroscience and Neurology, Barrow Neurological Institute, Phoenix, AZ, USA.
Stephen D GinsbergCenter for Dementia Research, Nathan Kline Institute, Orangeburg, NY, USA; NYU Neuroscience Institute, New York University Grossman School of Medicine, New York, NY, USA; Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA; Department of Neuroscience & Physiology, New York University Grossman School of Medicine, New York, NY, USA. Electronic address: ginsberg@nki.rfmh.org.

Funding

Uncovering Alzheimer's disease risk mechanisms through neuron-specific analysis of autophagy and endosomal-lysosomal functionP01AG017617 · NIA · NATHAN S. KLINE INSTITUTE FOR PSYCH RES · PI NIXON, RALPH A. · 2000 to 2021
$40.0M
TAU, AB, SYNUCLEIN AND NITRATIVE/OXIDATIVE DAMAGE IN MCIP01AG014449 · NIA · UNIVERSITY OF PITTSBURGH · PI IKONOMOVIC, MILOS D · 1997 to 2024
$39.7M
Impact of sex differences on the trajectory of interactome dysfunctions across the AD spectrumR01AG074004 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI CHIOSIS, GABRIELA, GINSBERG, STEPHEN D · 2021 to 2025
$6.0M
Chaperome networks in Alzheimer's diseaseR01AG067598 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI ARANCIO, OTTAVIO, CHIOSIS, GABRIELA · 2021 to 2025
$5.9M
Selective interactome vulnerability across the Alzheimer’s disease spectrumR01AG072599 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI GABRIELA CHIOSIS, STEPHEN D GINSBERG · 2023 to 2026
$5.4M
Neuropathology and inflammation in a nonhuman primate model of insulin resistance/metabolic syndromeR01AG085572 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI STEPHEN D GINSBERG, PETER J HAVEL · 2024 to 2026
$3.8M
Tau pathology in Down syndrome and Alzheimer'sRF1AG061566 · NIA · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI GRANHOLM-BENTLEY, ANN-CHARLOTTE ESTHER, MARGITTAI, MARTIN · 2019 to 2019
$3.4M
Septhohippocamal connectome dysfunction in Down syndrome associated with Alzheimer’s disease pathophysiologyRF1AG077103 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI GINSBERG, STEPHEN D, STUTZMANN, GRACE E. · 2023 to 2023
$2.5M
Default mode network dysfunction in Down SyndromeRF1AG081286 · NIA · ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER · PI MUFSON, ELLIOTT JAY, PEREZ, SYLVIA EVA · 2023 to 2023
$1.8M
Selective interactome vulnerability across the Alzheimer’s disease spectrumR56AG072599 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI CHIOSIS, GABRIELA, GINSBERG, STEPHEN D · 2021 to 2021
$1.2M
NIA NIH HHS P01 AG014449NIA NIH HHS P01 AG017617NIA NIH HHS R01 AG067598NIA NIH HHS R01 AG072599NIA NIH HHS R01 AG074004NIA NIH HHS R01 AG085572NIA NIH HHS R56 AG072599NIA NIH HHS RF1 AG061566NIA NIH HHS RF1 AG077103NIA NIH HHS RF1 AG081286
6 · The paper itself

Abstract

Individuals with DS develop Alzheimer's disease (AD) neuropathology, including endosomal-lysosomal system abnormalities and degeneration of basal forebrain cholinergic neurons (BFCNs). We investigated whether maternal choline supplementation (MCS) affects early endosome pathology within BFCNs using the Ts65Dn mouse model of DS/AD. Ts65Dn and disomic (2N) offspring from dams administered MCS were analyzed for endosomal pathology at 3-4 months or 10-12 months. Morphometric analysis of early endosome phenotype was performed on individual BFCNs using Imaris. The effects of MCS on the endosomal interactome were interrogated by relative co-expression (RCE) analysis. MCS effectively reduced age- and genotype-associated increases in early endosome number in Ts65Dn and 2N offspring, and prevented increases in early endosome size in Ts65Dn offspring. RCE revealed a loss of interactome cooperativity among endosome genes in Ts65Dn offspring that was restored by MCS. These findings demonstrate MCS rescues early endosome pathology, a driver of septohippocampal circuit dysfunction. The genotype-independent benefits of MCS on endosomal phenotype indicate translational applicability as an early-life therapy for DS as well as other neurodevelopmental/neurodegenerative disorders involving endosomal pathology.

Indexed as

Alzheimer DiseaseBasal ForebrainCholineCholinergic NeuronsDisease Models, AnimalDown SyndromeEndosomesAnimalsDietary SupplementsFemaleMaleMiceMice, TransgenicPregnancyCholine3D-reconstructionAlzheimer’s diseaseBasal forebrain cholinergic neuronDown syndromeEarly endosomeMaternal choline supplementation

Identifiers

PMID39265450
PMCPMC11490376

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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.