Dissecting the Crosstalk between Endothelial Mitochondrial Damage, Vascular Inflammation, and Neurodegeneration in Cerebral Amyloid Angiopathy and Alzheimer’s Disease

Rebecca M. Parodi-Rullán; Sabzali Javadov; Silvia Fossati

doi:10.3390/cells10112903

journal article Open Access Oct 27, 2021

Dissecting the Crosstalk between Endothelial Mitochondrial Damage, Vascular Inflammation, and Neurodegeneration in Cerebral Amyloid Angiopathy and Alzheimer’s Disease

Rebecca M. Parodi-Rullán

Sabzali Javadov

Silvia Fossati

Cells Vol. 10 No. 11 pp. 2903 · MDPI AG

View at Publisher Save 10.3390/cells10112903

Abstract

Alzheimer’s disease (AD) is the most prevalent cause of dementia and is pathologically characterized by the presence of parenchymal senile plaques composed of amyloid β (Aβ) and intraneuronal neurofibrillary tangles of hyperphosphorylated tau protein. The accumulation of Aβ also occurs within the cerebral vasculature in over 80% of AD patients and in non-demented individuals, a condition called cerebral amyloid angiopathy (CAA). The development of CAA is associated with neurovascular dysfunction, blood–brain barrier (BBB) leakage, and persistent vascular- and neuro-inflammation, eventually leading to neurodegeneration. Although pathologically AD and CAA are well characterized diseases, the chronology of molecular changes that lead to their development is still unclear. Substantial evidence demonstrates defects in mitochondrial function in various cells of the neurovascular unit as well as in the brain parenchyma during the early stages of AD and CAA. Dysfunctional mitochondria release danger-associated molecular patterns (DAMPs) that activate a wide range of inflammatory pathways. In this review, we gather evidence to postulate a crucial role of the mitochondria, specifically of cerebral endothelial cells, as sensors and initiators of Aβ-induced vascular inflammation. The activated vasculature recruits circulating immune cells into the brain parenchyma, leading to the development of neuroinflammation and neurodegeneration in AD and CAA.

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Details

Published: Oct 27, 2021
Vol/Issue: 10(11)
Pages: 2903
License: View

Authors

R

Rebecca M. Parodi-Rullán

Alzheimer’s Center at Temple, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA

S

Sabzali Javadov

Department of Physiology, University of Puerto Rico School of Medicine, San Juan, PR 00921, USA

S

Silvia Fossati

Alzheimer’s Center at Temple, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA

Funding

National Institutes of Health Award: R01NS104127

Edward N. and Della L. Thome Memorial Foundation Award in Alzheimer’s Disease Drug Discovery Research Award: NA

Pennsylvania Department of Heath Collaborative Research on Alzheimer’s Disease Award: 4100087336

the Karen Toffler Charitable Trust Award: NA

Lemole Center for Integrated Lymphatics research Award: NA

Cite This Article

Rebecca M. Parodi-Rullán, Sabzali Javadov, Silvia Fossati (2021). Dissecting the Crosstalk between Endothelial Mitochondrial Damage, Vascular Inflammation, and Neurodegeneration in Cerebral Amyloid Angiopathy and Alzheimer’s Disease. Cells, 10(11), 2903. https://doi.org/10.3390/cells10112903

Dissecting the Crosstalk between Endothelial Mitochondrial Damage, Vascular Inflammation, and Neurodegeneration in Cerebral Amyloid Angiopathy and Alzheimer’s Disease

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