Evidence map›Paper›PMID 38187716›Full record

ArticlebioRxiv : the preprint server for biology2023

Characterizing Molecular and Synaptic Signatures in mouse models of Late-Onset Alzheimer's Disease Independent of Amyloid and Tau Pathology.

Kevin P Kotredes, Ravi S Pandey, Scott Persohn, Kierra Elderidge, Charles P Burton, Ethan W Miner, Kathryn A Haynes, Diogo Francisco S Santos, Sean-Paul Williams, Nicholas Heaton and 15 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 6 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 5 institutions in 1 country.

Kevin P KotredesThe Jackson Laboratory, 600 Main Street, Bar Harbor, ME, United States, 04609.
Ravi S PandeyThe Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT, United States 06032.
Scott PersohnIndiana University School of Medicine, 340 W 10 Street, Indianapolis, IN, United States 46202.
Kierra ElderidgeIndiana University School of Medicine, 340 W 10 Street, Indianapolis, IN, United States 46202.
Charles P BurtonIndiana University School of Medicine, 340 W 10 Street, Indianapolis, IN, United States 46202.
Ethan W MinerIndiana University School of Medicine, 340 W 10 Street, Indianapolis, IN, United States 46202.
Kathryn A HaynesDepartment of Medicine, University of Pittsburgh Aging Institute, University of Pittsburgh School of Medicine, 100 Technology Drive, Pittsburgh, PA Pittsburgh, PA, United States 15219.
Diogo Francisco S SantosDepartment of Medicine, University of Pittsburgh Aging Institute, University of Pittsburgh School of Medicine, 100 Technology Drive, Pittsburgh, PA Pittsburgh, PA, United States 15219.
Sean-Paul WilliamsDepartment of Medicine, University of Pittsburgh Aging Institute, University of Pittsburgh School of Medicine, 100 Technology Drive, Pittsburgh, PA Pittsburgh, PA, United States 15219.
Nicholas HeatonDepartment of Medicine, University of Pittsburgh Aging Institute, University of Pittsburgh School of Medicine, 100 Technology Drive, Pittsburgh, PA Pittsburgh, PA, United States 15219.
Cynthia M IngrahamStark Neurosciences Research Institute, 320 W 15 Street, Indianapolis, IN, United States 46202.
Christopher LloydStark Neurosciences Research Institute, 320 W 15 Street, Indianapolis, IN, United States 46202.
Dylan GarceauThe Jackson Laboratory, 600 Main Street, Bar Harbor, ME, United States, 04609.
Rita O'RourkeThe Jackson Laboratory, 600 Main Street, Bar Harbor, ME, United States, 04609.
Sarah HerrickThe Jackson Laboratory, 600 Main Street, Bar Harbor, ME, United States, 04609.
Claudia Rangel-BarajasIndiana University School of Medicine, 340 W 10 Street, Indianapolis, IN, United States 46202.
Surendra MaharjanIndiana University School of Medicine, 340 W 10 Street, Indianapolis, IN, United States 46202.
Nian WangIndiana University School of Medicine, 340 W 10 Street, Indianapolis, IN, United States 46202.
Michael SasnerThe Jackson Laboratory, 600 Main Street, Bar Harbor, ME, United States, 04609.
Bruce T LambIndiana University School of Medicine, 340 W 10 Street, Indianapolis, IN, United States 46202.
Paul R TerritoIndiana University School of Medicine, 340 W 10 Street, Indianapolis, IN, United States 46202.
Stacey J Sukoff RizzoDepartment of Medicine, University of Pittsburgh Aging Institute, University of Pittsburgh School of Medicine, 100 Technology Drive, Pittsburgh, PA Pittsburgh, PA, United States 15219.
Gregory W CarterThe Jackson Laboratory, 600 Main Street, Bar Harbor, ME, United States, 04609.ORCID 0000-0002-2834-8186
Gareth R HowellThe Jackson Laboratory, 600 Main Street, Bar Harbor, ME, United States, 04609.ORCID 0000-0003-0565-6474
Adrian L OblakIndiana University School of Medicine, 340 W 10 Street, Indianapolis, IN, United States 46202.ORCID 0000-0003-1210-8791
Neurosciences Institute · USJackson Laboratory · USUniversity of Pittsburgh · USTufts University · USUniversity School · US

Funding

The IU/JAX Alzheimer's Disease Precision Models Center: Rat F344U54AG054345 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI Bruce T Lamb · 2016 to 2026
$95.6M
Vascular Structure and Function in Cognitive AgingP01AG003949 · NIA · YESHIVA UNIVERSITY · PI Charles B Hall · 1985 to 2026
$73.9M
SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI PETERSEN, RONALD C · 1999 to 2018
$36.9M
Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5M
Research Education ComponentP30AG072980 · NIA · BANNER HEALTH · PI Nicholas Ashton · 2021 to 2026
$24.9M
Integrating the exposome and methylome to inform brain molecular changes in ADRD across established diverse cohorts.U01AG046139 · NIA · UNIVERSITY OF FLORIDA · PI ERTEKIN-TANER, NILUFER, FUNK, CORY · 2013 to 2022
$24.6M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
TRANSGENIC MODELING OF TAUOPATHYP01AG017216 · NIA · MAYO CLINIC JACKSONVILLE · PI DICKSON, DENNIS WILLIAM · 1999 to 2011
$12.0M
PREDICTORS OF THE RATE OF COGNITIVE DECLINE IN ELDERLY SUBJECTSP50AG025711 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI POTTER, HUNTINGTON · 2005 to 2010
$8.2M
NIA NIH HHS P01 AG003949NIA NIH HHS P01 AG017216NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG072980NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG025711NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG018023NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG036836NIA NIH HHS U01 AG006786NIA NIH HHS U01 AG046139NIA NIH HHS U54 AG054345NINDS NIH HHS R01 NS080820NINDS NIH HHS R01 NS125020NINDS NIH HHS U24 NS072026
6 · The paper itself

Abstract

introductionMODEL-AD is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to more accurately mimic LOAD than commonly used transgenic models.

methodsWe created the LOAD2 model by combining APOE4, Trem2*R47H, and humanized amyloid-beta. Mice aged up to 24 months were subjected to either a control diet or a high-fat/high-sugar diet (LOAD2+HFD) from two months of age. We assessed disease-relevant outcomes, including in vivo imaging, biomarkers, multi-omics, neuropathology, and behavior.

resultsBy 18 months, LOAD2+HFD mice exhibited cortical neuron loss, elevated insoluble brain Aβ42, increased plasma NfL, and altered gene/protein expression related to lipid metabolism and synaptic function. In vivo imaging showed age-dependent reductions in brain region volume and neurovascular uncoupling. LOAD2+HFD mice also displayed deficits in acquiring touchscreen-based cognitive tasks. DISCUSSION: Collectively the comprehensive characterization of LOAD2+HFD mice reveal this model as important for preclinical studies that target features of LOAD independent of amyloid and tau.

Indexed as

Alzheimer’s diseaseAPOE4geneticshigh-fat dietlate-onset Alzheimer’s diseaseLOADMODEL-ADTREM2

Identifiers

PMID38187716
PMCPMC10769232
OpenAlexW4389991094

What OpenQuestion holds

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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.