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A High Output Method to Isolate Cerebral Pericytes from Mouse
Published on: January 14, 2020
Pericyte loss influences Alzheimer-like neurodegeneration in mice
Abhay P Sagare1, Robert D Bell2, Zhen Zhao1
11] Department of Physiology and Biophysics, Keck School of Medicine, Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California 90033, USA [2].
Abstract:
Pericytes are cells in the blood-brain barrier that degenerate in Alzheimer's disease (AD), a neurological disorder associated with neurovascular dysfunction, abnormal elevation of amyloid β-peptide (Aβ), tau pathology and neuronal loss. Whether pericyte degeneration can influence AD-like neurodegeneration and contribute to disease pathogenesis remains, however, unknown. Here we show that in mice overexpressing Aβ-precursor protein, pericyte loss elevates brain Aβ40 and Aβ42 levels and accelerates amyloid angiopathy and cerebral β-amyloidosis by diminishing clearance of soluble Aβ40 and Aβ42 from brain interstitial fluid prior to Aβ deposition. We further show that pericyte deficiency leads to the development of tau pathology and an early neuronal loss that is normally absent in Aβ-precursor protein transgenic mice, resulting in cognitive decline. Our data suggest that pericytes control multiple steps of AD-like neurodegeneration pathogenic cascade in Aβ-precursor protein-overexpressing mice. Therefore, pericytes may represent a novel therapeutic target to modify disease progression in AD.
Insights
Pericyte degeneration in Alzheimer's disease (AD) worsens amyloid-beta levels and tau pathology. Targeting pericytes could offer a new therapeutic strategy for AD.
Area of Science:
- Neuroscience
- Pathology
- Cell Biology
Background:
- Pericytes are crucial blood-brain barrier cells that degenerate in Alzheimer's disease (AD).
- The role of pericyte degeneration in AD pathogenesis and neurodegeneration remains unclear.
- AD is characterized by neurovascular dysfunction, amyloid-beta (Aβ) and tau pathology, and neuronal loss.
Purpose of the Study:
- To investigate whether pericyte degeneration influences AD-like neurodegeneration.
- To determine if pericyte loss contributes to AD pathogenesis in a mouse model.
Main Methods:
- Utilized mice overexpressing amyloid precursor protein (APP).
- Assessed the impact of pericyte loss on Aβ levels, amyloid angiopathy, and tau pathology.
- Evaluated neuronal loss and cognitive function in the context of pericyte deficiency.
Main Results:
- Pericyte loss elevated brain Aβ40 and Aβ42 levels.
- Pericyte deficiency accelerated amyloid angiopathy and cerebral β-amyloidosis by impairing Aβ clearance.
- Pericyte deficiency induced tau pathology, early neuronal loss, and cognitive decline in APP transgenic mice.
Conclusions:
- Pericytes play a critical role in controlling multiple steps of the AD pathogenic cascade.
- Pericyte degeneration exacerbates key pathological features of AD.
- Pericytes represent a potential novel therapeutic target for modifying AD progression.
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