Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction
Einar Kleinhans Krogsaeter, Justin McKetney, Leopoldo Valiente‐Banuet, Angelica Marquez, Alexandra R. Willis, Zeynep Cakir, Erica J. Stevenson, Gwendolyn Μ. Jang et al.. Autophagy, 2025-10-17
Topic: Brain proteins, microglia and lab models
: Aβ-β-amyloid; AD-Alzheimer disease; APMS-affinity purification mass spectrometry; APOE-apolipoprotein E; APP-amyloid beta precursor protein; BafA1-bafilomycin A1; CMA-chaperone-mediated autophagy; COP-coatomer; ER-endoplasmic reticulum; ERAD-endoplasmic reticulum-associated degradation; ERGIC-endoplasmic reticulum-Golgi intermediate compartment; FCCP-carbonyl cyanide p-trifluoromethoxyphenylhydrazone; GABA-gamma-aminobutyric acid; GFP-green fluorescent protein; GPI-glycerophosphoinositol; GPN-glycyl-L-phenylalanine 2-naphthylamide; HA-hemagglutinin protein tag; iPSC-induced pluripotent stem cells; LAMP1-lysosomal associated membrane protein 1; LGALS3BP-galectin 3 binding protein; LysoIP-lysosomal immunoprecipitation; MAPT-microtubule associated protein tau; MR-CTSB-magic red cathepsin B; MS-mass spectrometry; NFT-neurofibrillary tangles; PCA-principal component analysis; PLA-proximity ligation assay; PSEN1-presenilin 1; PSEN2-presenilin 2; p-MAPT/Tau-phospho-MAPT/tau; ROS-reactive oxygen species; RT-qPCR-reverse transcriptase quantitative polymerase chain reaction; SEM-standard error of the mean; siRNA-short interfering RNA; SRCR-scavenger receptor cysteine-rich domain; TMED-transmembrane p24 trafficking protein; TMEM192-transmembrane protein 192.
Key findings
- : Aβ-β-amyloid; AD-Alzheimer disease; APMS-affinity purification mass spectrometry; APOE-apolipoprotein E; APP-amyloid beta precursor protein; BafA1-bafilomycin A1; CMA-chaperone-mediated autophagy; COP-coatomer; ER-endoplasmic reticulum; ERAD-endoplasmic reticulum-associated degradation; ERGIC-endo
Why it matters
This study used lysosomal proteomics to investigate how the APOE4 form of apolipoprotein E may cause lysosomal dysfunction in neurons. It is a laboratory study and does not report a treatment or prevention for Alzheimer disease.
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Study details
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Autophagy) |
| Journal's citation record | 2 / 4 | Autophagy: journal h-index 240 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 20 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 6.7 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 9.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 19 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Danielle L. Swaney: h-index 50 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California, Los Angeles: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41103078) |
| Free to read | 2 / 2 | Free to read |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Krogsaeter, E. K., McKetney, J., Valiente‐Banuet, L., Marquez, A., Willis, A. R., Cakir, Z., et al. (2025). Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction. Autophagy. https://doi.org/10.1080/15548627.2025.2576613
Vancouver
Krogsaeter EK, McKetney J, Valiente‐Banuet L, Marquez A, Willis AR, Cakir Z, et al. Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction. Autophagy. 2025. doi:10.1080/15548627.2025.2576613. PMID: 41103078.
BibTeX
@article{krogsaeter2025-41103078,
author = {Krogsaeter, Einar Kleinhans and McKetney, Justin and Valiente‐Banuet, Leopoldo and Marquez, Angelica and Willis, Alexandra R. and Cakir, Zeynep and Stevenson, Erica J. and Jang, Gwendolyn Μ. and others},
title = {{Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction}},
journal = {Autophagy},
year = {2025},
doi = {10.1080/15548627.2025.2576613},
pmid = {41103078},
url = {https://doi.org/10.1080/15548627.2025.2576613}
}
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