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The Alzheimer’s disease risk gene ABCA7 regulates microglial lysosomal and lipid homeostasis and promotes phagocytosis to maintain neuronal health
Heuer SE, Ahsan FM, Terzioglu G, Misra A, Duong D, Katkar C, Giera M, van der Kant R et al.. bioRxiv, 2026-10-19
Topic: Disease mechanisms in lab and animal studies
Background Loss of function mutations in the lipid transporter ABCA7 have been linked to increased risk for late onset Alzheimer’s disease (AD). Although rare and common variants in ABCA7 associated with AD alter the coding sequence and are predicted to impair protein function, the precise cell-type consequences of ABCA7 deficiency remain incompletely defined. Results ABCA7-KO iMGs were deficient for proteins involved in lysosome function, measured by down-regulated lysosomal proteomic signatures, as well as reduced DQ-BSA activity and reduced LAMP1+ area. This was complemented by an accumulation of polyunsaturated triacylglycerols and lipid droplets, suggesting that ABCA7 deficiency disrupts intracellular lipid dynamics. Concordantly, proteomic and functional analyses revealed lysosomal dysfunction in rs3752246-mutant iMGs, suggesting a shared ABCA7-dependent mechanism underlying AD risk. Tri-cultures of iNs, iAs and iMGs revealed that ABCA7 deficiency in iMGs worsened AD-relevant neuronal measures such as tau phosphorylation and synapse number.
Key findings
- Background Loss of function mutations in the lipid transporter ABCA7 have been linked to increased risk for late onset Alzheimer’s disease (AD).
- Although rare and common variants in ABCA7 associated with AD alter the coding sequence and are predicted to impair protein function, the precise cell-type consequences of ABCA7 deficiency remain incompletely defined.
- Results ABCA7-KO iMGs were deficient for proteins involved in lysosome function, measured by down-regulated lysosomal proteomic signatures, as well as reduced DQ-BSA activity and reduced LAMP1+ area.
- This was complemented by an accumulation of polyunsaturated triacylglycerols and lipid droplets, suggesting that ABCA7 deficiency disrupts intracellular lipid dynamics.
- Concordantly, proteomic and functional analyses revealed lysosomal dysfunction in rs3752246-mutant iMGs, suggesting a shared ABCA7-dependent mechanism underlying AD risk.
Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (bioRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| 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 | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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
Heuer, S. E., Ahsan, F. M., Terzioglu, G., Misra, A., Duong, D., Katkar, C., et al. (2026). The Alzheimer’s disease risk gene ABCA7 regulates microglial lysosomal and lipid homeostasis and promotes phagocytosis to maintain neuronal health. bioRxiv. https://doi.org/10.64898/2026.10.16.759681
Vancouver
Heuer SE, Ahsan FM, Terzioglu G, Misra A, Duong D, Katkar C, et al. The Alzheimer’s disease risk gene ABCA7 regulates microglial lysosomal and lipid homeostasis and promotes phagocytosis to maintain neuronal health. bioRxiv. 2026. doi:10.64898/2026.10.16.759681.
BibTeX
@article{heuer2026-8adbb044,
author = {Heuer, S. E. and Ahsan, F. M. and Terzioglu, G. and Misra, A. and Duong, D. and Katkar, C. and Giera, M. and van der Kant, R. and others},
title = {{The Alzheimer’s disease risk gene ABCA7 regulates microglial lysosomal and lipid homeostasis and promotes phagocytosis to maintain neuronal health}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.10.16.759681},
url = {https://doi.org/10.64898/2026.10.16.759681}
}
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