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Brain mural cell loss in the parietal cortex in Alzheimer’s disease correlates with cognitive decline and TDP‐43 pathology
- Source :
- Neuropathol Appl Neurobiol
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Aims Brain mural cells (BMC), smooth muscle cells and pericytes, interact closely with endothelial cells and modulate numerous cerebrovascular functions. A loss of BMC function is suspected to play a role in the pathophysiology of Alzheimer's Disease (AD). Methods BMC markers, namely smooth muscle alpha actin (α-SMA) for smooth muscle cells, as well as platelet-derived growth factor receptor β (PDGFRβ) and aminopeptidase N (ANPEP or CD13) for pericytes, were assessed by Western immunoblotting in microvessel extracts from the parietal cortex of 60 participants of the Religious Orders study, with ages at death ranging from 75 to 98 years old. Results Participants clinically diagnosed with AD had lower vascular levels of α-SMA, PDGFRβ and CD13. These reductions were correlated with lower cognitive scores for global cognition, episodic and semantic memory, perceptual speed and visuospatial ability. In addition, α-SMA, PDGFRβ and CD13 were negatively correlated with vascular Aβ40 concentrations. Vascular levels of BMC markers were also inversely correlated with insoluble cleaved phosphorylated transactive response DNA binding protein 43 (TDP-43) (25 kDa) and positively correlated with soluble cleaved phosphorylated TDP-43 (35 kDa) in cortical homogenates, suggesting strong association between BMC loss and cleaved phosphorylated TDP-43 aggregation. Conclusions The results of this study highlight a loss of BMC in AD. The associations between α-SMA, PDGFRβ and CD13 vascular levels with cognitive scores, TDP-43 aggregation and cerebrovascular accumulation of Aβ in the parietal cortex suggest that BMC loss contributes to both AD symptoms and pathology, further strengthening the link between cerebrovascular defects and dementia.
- Subjects :
- Male
0301 basic medicine
Pathology
medicine.medical_specialty
Histology
Myocytes, Smooth Muscle
Posterior parietal cortex
Article
Mural cell
Pathology and Forensic Medicine
Mice
03 medical and health sciences
0302 clinical medicine
Growth factor receptor
Alzheimer Disease
Parietal Lobe
Physiology (medical)
medicine
Animals
Humans
Dementia
Semantic memory
Cognitive Dysfunction
Cognitive decline
Microvessel
Aged, 80 and over
business.industry
medicine.disease
Pathophysiology
030104 developmental biology
Neurology
TDP-43 Proteinopathies
Female
Neurology (clinical)
Pericytes
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 13652990 and 03051846
- Volume :
- 46
- Database :
- OpenAIRE
- Journal :
- Neuropathology and Applied Neurobiology
- Accession number :
- edsair.doi.dedup.....f41927e2edd0782a6608fae8bbae0cef