Molecular pathways and diagnosis in spatially resolved Alzheimer's hippocampal atlas
Pan Wang, Lei Han, Lifang Wang, Quyuan Tao, Zhen Guo, Ting Luo, Youzhe He, Zhi Xu et al.. Neuron, 2025-03-31
Topic: Genetics and APOE
We employed Stereo-seq combined with single-nucleus RNA sequencing (snRNA-seq) to investigate the gene expression and cell composition changes in human hippocampus with or without Alzheimer's disease (AD). The transcriptomic map, with single-cell precision, unveiled AD-associated alterations with spatial specificity, which include the following: (1) elevated synapse pruning gene expression in the fimbria of AD, with disrupted microglia-astrocyte communication likely leading to disorganized synaptic structure; (2) a globally increased energy generation in the cornu ammonis (CA) region, with varying degrees across its subregions; (3) a significant reduction in the number of CA1 neurons in AD, while CA4 neurons remained largely unaffected, potentially due to gene alterations in CA4 conferring resilience to AD; and (4) aggravated amyloid-beta (Aβ) plaques in CA1 and stratum lucidum, radiatum, and moleculare (SLRM), and integration of Stereo-seq map with Aβ staining revealed a sequential enrichment of microglia and astrocytes around Aβ plaques. Finally, reduced brain-derived extracellular vesicles carrying cholecystokinin (CCK) and peripheral myelin protein 2 (PMP2) in AD plasma highlighted their diagnostic potential for clinical applications.
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APA 7th
Wang, P., Han, L., Wang, L., Tao, Q., Guo, Z., Luo, T., et al. (2025). Molecular pathways and diagnosis in spatially resolved Alzheimer's hippocampal atlas. Neuron. https://doi.org/10.1016/j.neuron.2025.03.002
Vancouver
Wang P, Han L, Wang L, Tao Q, Guo Z, Luo T, et al. Molecular pathways and diagnosis in spatially resolved Alzheimer's hippocampal atlas. Neuron. 2025. doi:10.1016/j.neuron.2025.03.002. PMID: 40168986.
BibTeX
@article{wang2025-40168986,
author = {Wang, Pan and Han, Lei and Wang, Lifang and Tao, Quyuan and Guo, Zhen and Luo, Ting and He, Youzhe and Xu, Zhi and others},
title = {{Molecular pathways and diagnosis in spatially resolved Alzheimer's hippocampal atlas}},
journal = {Neuron},
year = {2025},
doi = {10.1016/j.neuron.2025.03.002},
pmid = {40168986},
url = {https://doi.org/10.1016/j.neuron.2025.03.002}
}
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Key findings
- The transcriptomic map, with single-cell precision, unveiled AD-associated alterations with spatial specificity, which include the following: (1) elevated synapse pruning gene expression in the fimbria of AD, with disrupted microglia-astrocyte communication likely leading to disorganized synaptic structure; (2) a globally increased energy generation in the cornu ammonis (CA) region, with varying degrees across its subregions; (3) a significant reduction in the number of CA1 neurons in AD, while CA4 neurons remained largely unaffected, potentially due to gene alterations in CA4 conferring resilience to AD; and (4) aggravated amyloid-beta (Aβ) plaques in CA1 and stratum lucidum, radiatum, and moleculare (SLRM), and integration of Stereo-seq map with Aβ staining revealed a sequential enrichment of microglia and astrocytes around Aβ plaques.
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Study details
- Evidence strengthLow
How this study scored 43/100
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. We have no data on journal's citation record, 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, multi-centre collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuron) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | — / 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 | 2 / 2 | Indexed in PubMed (PMID 40168986) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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