ArticlebioRxiv : the preprint server for biology2024
Multifaceted impact of specialized neuropeptide-intensive neurons on the selective vulnerability in Alzheimer's disease.
Manci Li, Nichole Flack, Peter A Larsen
Open access · greenAbstract readPreprint
In one paragraphArticle in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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What it found
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2 · The registryThe trial behind it
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
3 authors at 1 institution in 1 country.
Manci LiDepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108.ORCID 0000-0003-3930-7117 Nichole FlackDepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108.ORCID 0000-0002-4213-5195 Peter A LarsenDepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, MN 55108.
University of Minnesota · US
Funding
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MRush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7MRISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4MMulti-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7MPathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6MIdentification of TDP-43 Modifiers Through Single-Cell Transcriptional and Epigenomic Dissection of ALS and FTLD-MNDR01NS127187 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BELZIL, VERONIQUE, DONNELLY, CHRISTOPHER JAMES · 2021 to 2025
$9.1MEpigenomic, transcriptional and cellular dissection of Alzheimer's variantsR01AG058002 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI HYMAN, BRADLEY T., JAENISCH, RUDOLF · 2017 to 2021
$7.9MElucidating the Molecular Mechanisms of Neuropsychiatric Symptoms in Alzheimer's DiseaseR01AG062335 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KELLIS, MANOLIS, TSAI, LI-HUEI · 2018 to 2022
$6.5MSingle-cell epigenomic and trancriptional dissection of sex-specific differences in Alzheimer’s DiseaseR01AG074003 · NIA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KELLIS, MANOLIS, TSAI, LI-HUEI · 2021 to 2025
$5.4MGraduate Training in Computational and Systems BiologyT32GM087237 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BURGE, CHRISTOPHER B · 2009 to 2023
$4.6MSingle-cell transcriptional and epigenomic dissection of Alzheimer's Disease and Related DementiasU01NS110453 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI KELLIS, MANOLIS, TSAI, LI-HUEI · 2018 to 2020
$4.0MNHGRI NIH HHS R01 HG008155NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG058002NIA NIH HHS R01 AG062335NIA NIH HHS R01 AG074003NIA NIH HHS RF1 AG054012NIA NIH HHS RF1 AG054321NIA NIH HHS RF1 AG062377NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG061356NIGMS NIH HHS T32 GM087237NIMH NIH HHS U01 MH119509NINDS NIH HHS R01 NS127187NINDS NIH HHS U01 NS110453NINDS NIH HHS UG3 NS115064NINDS NIH HHS UH3 NS115064
6 · The paper itselfAbstract
introductionWidespread disruption of neuropeptide (NP) networks in Alzheimer's disease (AD) and disproportionate absence of neurons expressing
methodsMultiscale and spatiotemporal transcriptomic analysis was used to investigate AD-afflicted and healthy brains. Our focus encompassed NP expression dynamics in AD,
resultsFindings include that 1) HNP neurons exhibited heightened metabolic needs and an upregulation of gene expressions linked to protein misfolding; 2) dysfunctions of ADNP production occurred in aging and mild cognitive decline; 3) HNP neurons co-expressing ADNPs were preferentially distributed in brain regions susceptible to AD. DISCUSSION: We identified potential mechanisms that contribute to the selective vulnerability of HNP neurons to AD. Our results indicate that the functions of HNP neurons predispose them to oxidative stress and protein misfolding, potentially serving as inception sites for misfolded proteins in AD.
Identifiers
PMID38014130
PMCPMC10680689
OpenAlexW4388745165
What Socratic holds
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