Omics · study · 2026
A Scalable Human Brain Cell Atlas Dissects the Microglial Immune Codes and Cognitive Resilience
Listed in NCBI GEO
The biological basis of resilience to cognitive decline and Alzheimer’s disease (AD) remains unclear, hindering the development of effective interventions for brain health.
Description
Here, we present the largest human brain single-nucleus RNA-seq atlas to date (~14 million nuclei across 31 brain regions from 2,239 deeply phenotyped postmortem samples, including cognitively normal (CN), AD (clinico-pathologically confirmed), cognitively resilient (CR), and primary age-related tauopathy (PART)), using a scalable generative artificial intelligence framework.
This resource identifies >50 neuronal and glial cell types and reveals a linkage of mitochondrial bioenergetics in somatostatin (SST) neurons to cognitive resilience in the presence of amyloid-beta and tau pathology, which we validated immunohistochemically. We also identified that the microglia-associated genes PLCG2 and GPNMB were associated with AD progression in an age-independent manner. Genes encoding interferon signaling pathways (e.g., IFIT3 and IFI44) were identified as female-specific markers in disease-associated microglia.
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We also identified glutamate signaling-mediated immune-neuron crosstalks associated with AD etiologies, which was experimentally validated by transcriptomic signatures in patient iPSC-derived microglia. In summary, this comprehensive brain cell atlas deciphers brain-immune interactions underlying brain resilience and offers an open-access platform to accelerate therapeutic development for AD and brain health if broadly applied.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326002 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326002 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1442802 ncbi.nlm.nih.gov/bioproject/PRJNA1442802 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Disease 75% · RNA sequencing 65% · Single-cell RNA sequencing 65%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE326002 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |