Vasomotion as a Driving Force for Paravascular Clearance in the Awake Mouse Brain DOI Creative Commons
Susanne J. van Veluw,

Steven S. Hou,

Maria Calvo‐Rodriguez

et al.

Neuron, Journal Year: 2019, Volume and Issue: 105(3), P. 549 - 561.e5

Published: Dec. 3, 2019

Paravascular drainage of solutes, including β-amyloid (Aβ), appears to be an important process in brain health and diseases such as Alzheimer's disease (AD) cerebral amyloid angiopathy (CAA). However, the major driving force for clearance remains largely unknown. Here we used vivo two-photon microscopy awake head-fixed mice assess role spontaneous vasomotion paravascular clearance. Vasomotion correlated with fluorescent dextran from interstitial fluid. Increasing amplitude by means visually evoked vascular responses resulted increased rates visual cortex mice. Evoked reactivity was impaired CAA, which corresponded slower rates. Our findings suggest that low-frequency arteriolar oscillations drive solutes. Targeting naturally occurring patients CAA or AD may a promising early therapeutic option prevention Aβ accumulation brain.

Language: Английский

Alzheimer's disease DOI
Philip Scheltens, Bart De Strooper, Miia Kivipelto

et al.

The Lancet, Journal Year: 2021, Volume and Issue: 397(10284), P. 1577 - 1590

Published: March 2, 2021

Language: Английский

Citations

3039
Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? DOI

Fangda Leng,

Paul Edison

Nature Reviews Neurology, Journal Year: 2020, Volume and Issue: 17(3), P. 157 - 172

Published: Dec. 14, 2020

Language: Английский

Citations

2069
Blood-Brain Barrier: From Physiology to Disease and Back DOI Open Access
Melanie D. Sweeney, Zhen Zhao, Axel Montagne

et al.

Physiological Reviews, Journal Year: 2018, Volume and Issue: 99(1), P. 21 - 78

Published: Oct. 3, 2018

The blood-brain barrier (BBB) prevents neurotoxic plasma components, blood cells, and pathogens from entering the brain. At same time, BBB regulates transport of molecules into out central nervous system (CNS), which maintains tightly controlled chemical composition neuronal milieu that is required for proper functioning. In this review, we first examine molecular cellular mechanisms underlying establishment BBB. Then, focus on physiology, endothelial pericyte transporters, perivascular paravascular transport. Next, discuss rare human monogenic neurological disorders with primary genetic defect in BBB-associated cells demonstrating link between breakdown neurodegeneration. review effects genes inheritance and/or increased susceptibility Alzheimer's disease (AD), Parkinson's (PD), Huntington's disease, amyotrophic lateral sclerosis (ALS) relation to other pathologies deficits. We next how dysfunction relates deficits majority sporadic AD, PD, ALS cases, multiple sclerosis, neurodegenerative disorders, acute CNS such as stroke, traumatic brain injury, spinal cord epilepsy. Lastly, BBB-based therapeutic opportunities. conclude lessons learned future directions, emphasis technological advances investigate functions living brain, at level, address key unanswered questions.

Language: Английский

Citations

1670
Blood–brain barrier breakdown is an early biomarker of human cognitive dysfunction DOI
Daniel A. Nation, Melanie D. Sweeney, Axel Montagne

et al.

Nature Medicine, Journal Year: 2019, Volume and Issue: 25(2), P. 270 - 276

Published: Jan. 8, 2019

Language: Английский

Citations

1302
The Amyloid-β Pathway in Alzheimer’s Disease DOI Creative Commons
Harald Hampel, John Hardy, Kaj Blennow

et al.

Molecular Psychiatry, Journal Year: 2021, Volume and Issue: 26(10), P. 5481 - 5503

Published: Aug. 30, 2021

Abstract Breakthroughs in molecular medicine have positioned the amyloid-β (Aβ) pathway at center of Alzheimer’s disease (AD) pathophysiology. While detailed mechanisms and spatial-temporal dynamics leading to synaptic failure, neurodegeneration, clinical onset are still under intense investigation, established biochemical alterations Aβ cycle remain core biological hallmark AD promising targets for development disease-modifying therapies. Here, we systematically review update vast state-of-the-art literature science with evidence from basic research studies human genetic multi-modal biomarker investigations, which supports a crucial role dyshomeostasis pathophysiological dynamics. We discuss highlighting differentiated interaction distinct species other AD-related mechanisms, such as tau-mediated, neuroimmune inflammatory changes, well neurochemical imbalance. Through lens latest multimodal vivo biomarkers AD, this cross-disciplinary examines compelling hypothesis- data-driven rationale Aβ-targeting therapeutic strategies early treatment AD.

Language: Английский

Citations

1041
Single-Cell Transcriptome Atlas of Murine Endothelial Cells DOI Creative Commons
Joanna Kalucka, Laura de Rooij,

Jermaine Goveia

et al.

Cell, Journal Year: 2020, Volume and Issue: 180(4), P. 764 - 779.e20

Published: Feb. 1, 2020

Language: Английский

Citations

1009
APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline DOI
Axel Montagne, Daniel A. Nation, Abhay P. Sagare

et al.

Nature, Journal Year: 2020, Volume and Issue: 581(7806), P. 71 - 76

Published: April 29, 2020

Language: Английский

Citations

950
The role of brain vasculature in neurodegenerative disorders DOI
Melanie D. Sweeney, Kassandra Kisler, Axel Montagne

et al.

Nature Neuroscience, Journal Year: 2018, Volume and Issue: 21(10), P. 1318 - 1331

Published: Sept. 19, 2018

Language: Английский

Citations

806
Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease DOI Creative Commons
Marcelo A. Mori, Raissa G. Ludwig, Rubén García-Martín

et al.

Cell Metabolism, Journal Year: 2019, Volume and Issue: 30(4), P. 656 - 673

Published: Aug. 22, 2019

Language: Английский

Citations

719
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease DOI Creative Commons
Tiantian Guo, Denghong Zhang,

Yuzhe Zeng

et al.

Molecular Neurodegeneration, Journal Year: 2020, Volume and Issue: 15(1)

Published: July 16, 2020

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disorder seen in age-dependent dementia. There currently no effective treatment for AD, which may be attributed part to lack of a clear underlying mechanism. Studies within last few decades provide growing evidence central role amyloid β (Aβ) and tau, as well glial contributions various molecular cellular pathways AD pathogenesis. Herein, we review recent progress with respect Aβ- tau-associated mechanisms, discuss dysfunction emphasis on neuronal receptors that mediate Aβ-induced toxicity. We also other critical factors affect pathogenesis, including genetics, aging, variables related environment, lifestyle habits, describe potential apolipoprotein E (APOE), viral bacterial infection, sleep, microbiota. Although have gained much towards understanding aspects this devastating disorder, greater commitment research mechanism, diagnostics will needed future research.

Language: Английский

Citations

703