Evidence map›Paper›PMID 37873080›Full record

ArticlebioRxiv : the preprint server for biology2025

Lysosomal proteomics reveals mechanisms of neuronal apoE4-associated lysosomal dysfunction.

Einar K Krogsaeter, Justin McKetney, Leopoldo Valiente-Banuet, Angelica Marquez, Alexandra Willis, Zeynep Cakir, Erica Stevenson, Gwendolyn M Jang, Antara Rao, Emmy Li and 7 more

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

Article in bioRxiv : the preprint server for biology, 2025. 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, 7 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 1 country.

Einar K KrogsaeterGladstone Data Science and Biotechnology Institute, The J. David Gladstone Institutes, San Francisco, California, USA.ORCID 0000-0001-8232-5498
Justin McKetneyGladstone Data Science and Biotechnology Institute, The J. David Gladstone Institutes, San Francisco, California, USA.
Leopoldo Valiente-BanuetDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Angelica MarquezGladstone Data Science and Biotechnology Institute, The J. David Gladstone Institutes, San Francisco, California, USA.
Alexandra WillisGladstone Data Science and Biotechnology Institute, The J. David Gladstone Institutes, San Francisco, California, USA.
Zeynep CakirGladstone Data Science and Biotechnology Institute, The J. David Gladstone Institutes, San Francisco, California, USA.
Erica StevensonGladstone Data Science and Biotechnology Institute, The J. David Gladstone Institutes, San Francisco, California, USA.
Gwendolyn M JangGladstone Data Science and Biotechnology Institute, The J. David Gladstone Institutes, San Francisco, California, USA.
Antara RaoGladstone Institute of Neurological Disease, The J. David Gladstone Institutes, San Francisco, USA.
Emmy LiInstitute for Neurodegenerative Diseases, University of California, San Francisco, California, USA.
Anton ZhouGladstone Institute of Neurological Disease, The J. David Gladstone Institutes, San Francisco, USA.
Anjani AttiliInstitute for Neurodegenerative Diseases, University of California, San Francisco, California, USA.
Timothy S ChangDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.ORCID 0000-0002-9225-9874
Martin KampmannInstitute for Neurodegenerative Diseases, University of California, San Francisco, California, USA.ORCID 0000-0002-3819-7019
Yadong HuangGladstone Institute of Neurological Disease, The J. David Gladstone Institutes, San Francisco, USA.
Nevan J KroganGladstone Data Science and Biotechnology Institute, The J. David Gladstone Institutes, San Francisco, California, USA.ORCID 0000-0003-4902-337X
Danielle L SwaneyGladstone Data Science and Biotechnology Institute, The J. David Gladstone Institutes, San Francisco, California, USA.ORCID 0000-0001-6119-6084
Gladstone Institutes · USUniversity of California, Los Angeles · USUniversity of California, San Francisco · USCity College of San Francisco · US

Funding

Research Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Katherine P Rankin · 2019 to 2026
$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 ALIREZA ATRI · 2021 to 2026
$24.9M
Uncovering the Genetic Mechanisms of the Chromosome 17q21.31 Tau Haplotype on Neurodegeneration Risk in FTD and PSPU54NS123746 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GRINBERG, LEA TENENHOLZ · 2021 to 2025
$9.4M
National Brain and Tissue Resource for Parkinson's Disease and Related DisordersU24NS072026 · NINDS · BANNER SUN HEALTH RESEARCH INSTITUTE · PI BEACH, THOMAS G · 2011 to 2015
$7.8M
PREDOCTORAL TRAINING IN DEVELOPMENTAL BIOLOGYT32HD007470 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Todd Nystul · 1994 to 2026
$7.7M
Proteomic and Genetic Approaches Defining Apolipoprotein E4 Neuropathologic MechanismsRF1AG059751 · NIA · J. DAVID GLADSTONE INSTITUTES · PI KROGAN, NEVAN J, MAHLEY, ROBERT W. · 2019 to 2019
$4.7M
Neuronal ApoE Drives Selective Neurodegeneration in Alzheimer's DiseaseR01AG071697 · NIA · J. DAVID GLADSTONE INSTITUTES · PI HUANG, YADONG · 2021 to 2025
$4.1M
Translational Neuroscience Training GrantR25NS065723 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CARMICHAEL, STANLEY THOMAS · 2009 to 2023
$2.8M
NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG072980NIA NIH HHS R01 AG071697NIA NIH HHS RF1 AG059751NICHD NIH HHS T32 HD007470NINDS NIH HHS R25 NS065723NINDS NIH HHS U24 NS072026NINDS NIH HHS U54 NS123746
6 · The paper itself

Abstract

ApoE4 is the primary risk factor for Alzheimer Disease (AD). Early AD pathological events first affect the neuronal endolysosomal system, which in turn causes neuronal protein aggregation and cell death. Despite the crucial influence of lysosomes upon AD pathophysiology, and that apoE4 localizes to lysosomes, the influence of apoE4 on lysosomal function remains unexplored. We find that expression of apoE4 in neuronal cell lines results in lysosomal alkalinization and impaired lysosomal function. To identify driving factors for these defects, we performed quantitative lysosomal proteome profiling. This revealed that apoE4 expression results in differential regulation of numerous lysosomal proteins, correlating with apoE allele status and disease severity in AD brains. In particular, apoE4 expression results in the depletion of lysosomal Lgals3bp and the accumulation of lysosomal Tmed5. We additionally validated that these lysosomal protein changes can be targeted to modulate lysosomal function. Taken together, this work thereby reveals that apoE4 causes widespread lysosomal defects through remodeling the lysosomal proteome, with the lysosomal Tmed5 accumulation and Lgals3bp depletion manifesting as lysosomal alkalinization in apoE4 neurons.

Indexed as

Alzheimer DiseaseapoE4Lgals3bpLysoIPlysosomespHTmed5

Identifiers

PMID37873080
PMCPMC10592882
OpenAlexW4387242939

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.