| Title: | Population and single-cell analyses reveal immune cell-specific expression profiles associated with Alzheimer's disease risk |
|---|
| Authors: | ID Lindbohm, Joni V. (Author)
ID Stražar, Martin (Author)
ID Lee, Hang-Mao (Author)
ID Ashenberg, Orr (Author)
ID Mars, Nina (Author) |
|---|
| Files: |  URL - Source URL, visit https://doi.org/10.1002/alz.71282
 PDF - Presentation file, download (4,11 MB)
MD5: CC684CA3D3A0759E6434488449FCA336
|
|---|
| Language: | English |
|---|
| Typology: | 1.01 - Original Scientific Article |
|---|
| Organization: |  NIB - National Institute of Biology
|
|---|
| Abstract: | INTRODUCTION Dysregulation of the peripheral immune system may increase Alzheimer's disease (AD) risk, but the underlying cell type-specific mechanisms remain unclear. METHODS We conducted Mendelian randomization and colocalization analyses of 4489 genes using single-cell expression quantitative trait locus data from unstimulated and stimulated peripheral immune cells, integrated with an AD genome-wide association study (N = 455,258). Spatial transcriptomics of brain tissue samples was used to identify brain-infiltrating immune cells. RESULTS Thirteen genes were associated with AD risk. Expression of BIN1, CTSW, CTSH, HLA-DRB1, TSTD1, PLEKHA1, and SCIMP increased AD risk, while EPHA1-AS1, FCER1G, FIBP, KAT8, STX4, and HLA-DQA1 reduced it. These associations were peripheral immune cell type and state specific. PLEKHA1 and TSTD1 were upregulated and FIBP downregulated in natural killer and T cells in AD brain tissue. DISCUSSION These findings link immune cell-specific gene expression to AD risk across activation states and within brain-infiltrating immune cells, highlighting potential targets for immune-based AD prevention and treatment. |
|---|
| Publication status: | Published |
|---|
| Publication version: | Version of Record |
|---|
| Publication date: | 22.03.2026 |
|---|
| Year of publishing: | 2026 |
|---|
| Number of pages: | str. 1-14 |
|---|
| Numbering: | Vol. 22, iss. 3, [article no.] e71282 |
|---|
| PID: | 20.500.12556/DiRROS-28598  |
|---|
| UDC: | 616.8 |
|---|
| ISSN on article: | 1552-5279 |
|---|
| DOI: | 10.1002/alz.71282 |
|---|
| COBISS.SI-ID: | 272963843 |
|---|
| Note: | Slovenski soavtorji: Martin Stražar, Hang-Mao Lee, Orr Ashenberg, Nina Mars, Pyry N. Sipilä, Samuli Ripatti, Dan Graham, Mika Kivimäki, Ramnik J. Xavier;
Nasl. z nasl. zaslona;
Opis vira z dne 25. 3. 2026;
|
|---|
| Publication date in DiRROS: | 25.03.2026 |
|---|
| Views: | 188 |
|---|
| Downloads: | 120 |
|---|
| Metadata: |    |
|---|
|
:
|
Copy citation |
|---|
| | | | Share: |  |
|---|
Hover the mouse pointer over a document title to show the abstract or click
on the title to get all document metadata. |
