Abstract
Single Cell Approaches Reveal Perturbed Brain Vascular Molecules in Alzheimer’s Disease
Alzheimer's & dementia, Vol.18(S4), e063202
12/2022
DOI: 10.1002/alz.063202
Abstract
Background Inter‐cellular communication within the gliovascular unit (GVU) is critical for cerebral blood flow regulation, maintenance of the blood‐brain‐barrier (BBB) properties, and brain energy metabolism. Although numerous cell biology studies demonstrate the role of the GVU for BBB breakdown in Alzheimer’s disease (AD), the precise molecular changes contributing to its pathophysiology are unclear. Method We performed single nucleus RNA sequencing (snRNAseq) of temporal cortex tissue in 24 AD and control brains to understand the transcriptional changes in the cells of GVU. We acquired the snRNAseq profile of 79,751 total brain cells that comprise 6,541 astrocytes and 2,210 vascular cells. The latter formed three distinct vascular clusters characterized as activated pericytes, endothelia and resting pericytes. We identified differentially expressed genes (DEGs) and their enriched pathways in these clusters and detected the most transcriptional changes within activated pericytes. Using our data and a knowledge‐based predictive algorithm, we discovered and prioritized molecular interactions between vascular and astrocyte clusters, the main cell types of the GVU of the BBB. Results Vascular targets predicted to interact with astrocytic ligands have biological functions in signalling, angiogenesis, amyloid ß metabolism and cytoskeletal structure. Top astrocytic and vascular interacting molecules include both novel and known AD risk genes such as APOE, APP and ECE1. We validated gene expression changes using qPCR. We are in the process of evaluating these gene expression changes in antemortem blood from AD and control participants. Conclusion Our findings provide valuable information into the transcriptional changes in predicted vascular‐astrocytic partners at the GVU, highlighting insights into the molecular mechanisms of BBB breakdown in AD.
Details
- Title: Subtitle
- Single Cell Approaches Reveal Perturbed Brain Vascular Molecules in Alzheimer’s Disease
- Creators
- Özkan İş - Mayo Clinic in FloridaXue Wang - Mayo Clinic in FloridaJoseph S. Reddy - Mayo Clinic in FloridaTulsi Patel - Mayo Clinic in FloridaYuhao Min - Mayo Clinic in FloridaZachary Quicksall - Mayo Clinic in FloridaMichael G. Heckman - Mayo Clinic in FloridaLaunia White - Mayo Clinic in FloridaNaomi Kouri - Mayo Clinic in FloridaKaancan Deniz - Mayo Clinic in FloridaFrederick Q Tutor-New - Mayo Clinic in FloridaTroy Carnwath - Mayo Clinic in FloridaStephanie R Oatman - Mayo Clinic in FloridaMinerva M. Carrasquillo - Mayo Clinic in FloridaThuy Nguyen - Mayo Clinic in FloridaRonald C. Petersen - Mayo Clinic in ArizonaKejal Kantarci - Mayo Clinic in ArizonaKwangsik Nho - Indiana University School of MedicineAndrew J. Saykin - Indiana University – Purdue University IndianapolisDennis W. Dickson - Mayo Clinic in FloridaMelissa E. Murray - Mayo Clinic in FloridaMariet Allen - Mayo Clinic in FloridaNilufer Ertekin-Taner - Mayo Clinic in Florida
- Resource Type
- Abstract
- Publication Details
- Alzheimer's & dementia, Vol.18(S4), e063202
- DOI
- 10.1002/alz.063202
- ISSN
- 1552-5260
- eISSN
- 1552-5279
- Publisher
- Wiley
- Number of pages
- 1
- Language
- English
- Date published
- 12/2022
- Academic Unit
- Neurology
- Record Identifier
- 9985182278302771
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