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A lifespan single-cell atlas of the human developing hippocampus benchmarks familial Alzheimer’s disease brain organoids
Ivleva E, Kriukov E, Arboleda-Velasquez JF, Baranov P.. bioRxiv, 2026-09-20
Topic: Genetics and APOE
Familial Alzheimer’s disease (fAD) is an early-onset form of AD caused by autosomal-dominant variants in APP, PSEN1, or PSEN2, with PSEN1 accounting for most genetically defined cases [1]. The hippocampus is among the earliest and most severely affected brain regions in AD [2,3]. Human induced pluripotent stem cell (iPSC)-derived brain organoids recapitulate key features of early human brain development and provide a tractable model for studying how fAD mutations perturb neurodevelopmental processes [4]. However, their interpretation is complicated by heterogeneous regional identity, variable maturation state, and cell-type composition across protocols [5,6]. Existing single-cell studies of human hippocampus cover prenatal [7] and postnatal [8–10] stages but do not provide a continuous developmental reference. By elevating the atlas approach in utilizing single-cell RNA-sequencing data, we obtain standardized information on the organoid cell class and type composition and maturation states. Here, we constructed the Human Developing Hippocampus Atlas (HuDeHA), an integrated single-cell reference comprising 658,059 cells spanning post-conceptional week 3 to 15.3 years, and used it to benchmark iPSC-derived brain organoids carrying PSEN1 E280A which is associated with fAD in a large Colombian population. Reference-based mapping revealed altered cellular composition in PSEN1 E280A organoids, including reduced radial glia and increased neural crest-derived neurons. These changes were accompanied by cross-lineage transcriptional alterations, including broad upregulation of the ventral patterning factor MEIS2 and reduced expression of the Aβ-binding protein transthyretin (TTR) in choroid-plexus and ependymal-associated populations. Reconstructed neuronal-lineage trajectories showed a shift toward mature states in PSEN1 E280A organoids. Together, these findings establish HuDeHA as a resource for developmental benchmarking of hippocampus-relevant organoid systems and describe cell-lineage-specific developmental changes in PSEN1 E280A organoids that may inform interpretation of early cellular alterations in fAD.
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APA 7th
Ivleva, E., Kriukov, E., Arboleda-Velasquez, J. F., & Baranov, P. (2026). A lifespan single-cell atlas of the human developing hippocampus benchmarks familial Alzheimer’s disease brain organoids. bioRxiv. https://doi.org/10.64898/2026.09.18.752796
Vancouver
Ivleva E, Kriukov E, Arboleda-Velasquez JF, Baranov P. A lifespan single-cell atlas of the human developing hippocampus benchmarks familial Alzheimer’s disease brain organoids. bioRxiv. 2026. doi:10.64898/2026.09.18.752796.
BibTeX
@article{ivleva2026-322c5c1f,
author = {Ivleva, E. and Kriukov, E. and Arboleda-Velasquez, J. F. and Baranov, P.},
title = {{A lifespan single-cell atlas of the human developing hippocampus benchmarks familial Alzheimer’s disease brain organoids}},
journal = {bioRxiv},
year = {2026},
doi = {10.64898/2026.09.18.752796},
url = {https://doi.org/10.64898/2026.09.18.752796}
}
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Key findings
- Here, we constructed the Human Developing Hippocampus Atlas (HuDeHA), an integrated single-cell reference comprising 658,059 cells spanning post-conceptional week 3 to 15.3 years, and used it to benchmark iPSC-derived brain organoids carrying PSEN1 E280A which is associated with fAD in a large Colombian population.
- Reference-based mapping revealed altered cellular composition in PSEN1 E280A organoids, including reduced radial glia and increased neural crest-derived neurons.
- Together, these findings establish HuDeHA as a resource for developmental benchmarking of hippocampus-relevant organoid systems and describe cell-lineage-specific developmental changes in PSEN1 E280A organoids that may inform interpretation of early cellular alterations in fAD.
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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 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 | Laboratory or animal study (title names “organoids”) — scores zero |
| 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. |
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