Periarteriolar spaces modulate cerebrospinal fluid transport into brain and demonstrate altered morphology in aging and Alzheimer’s disease

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Periarteriolar spaces modulate cerebrospinal fluid transport into brain and demonstrate altered morphology in aging and Alzheimer’s disease. / Mestre, Humberto; Verma, Natasha; Greene, Thom D.; Lin, Li Jing A.; Ladron-de-Guevara, Antonio; Sweeney, Amanda M.; Liu, Guojun; Thomas, V. Kaye; Galloway, Chad A.; de Mesy Bentley, Karen L.; Nedergaard, Maiken; Mehta, Rupal I.

In: Nature Communications, Vol. 13, No. 1, 3897, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Mestre, H, Verma, N, Greene, TD, Lin, LJA, Ladron-de-Guevara, A, Sweeney, AM, Liu, G, Thomas, VK, Galloway, CA, de Mesy Bentley, KL, Nedergaard, M & Mehta, RI 2022, 'Periarteriolar spaces modulate cerebrospinal fluid transport into brain and demonstrate altered morphology in aging and Alzheimer’s disease', Nature Communications, vol. 13, no. 1, 3897. https://doi.org/10.1038/s41467-022-31257-9

APA

Mestre, H., Verma, N., Greene, T. D., Lin, L. J. A., Ladron-de-Guevara, A., Sweeney, A. M., Liu, G., Thomas, V. K., Galloway, C. A., de Mesy Bentley, K. L., Nedergaard, M., & Mehta, R. I. (2022). Periarteriolar spaces modulate cerebrospinal fluid transport into brain and demonstrate altered morphology in aging and Alzheimer’s disease. Nature Communications, 13(1), [3897]. https://doi.org/10.1038/s41467-022-31257-9

Vancouver

Mestre H, Verma N, Greene TD, Lin LJA, Ladron-de-Guevara A, Sweeney AM et al. Periarteriolar spaces modulate cerebrospinal fluid transport into brain and demonstrate altered morphology in aging and Alzheimer’s disease. Nature Communications. 2022;13(1). 3897. https://doi.org/10.1038/s41467-022-31257-9

Author

Mestre, Humberto ; Verma, Natasha ; Greene, Thom D. ; Lin, Li Jing A. ; Ladron-de-Guevara, Antonio ; Sweeney, Amanda M. ; Liu, Guojun ; Thomas, V. Kaye ; Galloway, Chad A. ; de Mesy Bentley, Karen L. ; Nedergaard, Maiken ; Mehta, Rupal I. / Periarteriolar spaces modulate cerebrospinal fluid transport into brain and demonstrate altered morphology in aging and Alzheimer’s disease. In: Nature Communications. 2022 ; Vol. 13, No. 1.

Bibtex

@article{652dac8787b54044ba494407255d37b7,
title = "Periarteriolar spaces modulate cerebrospinal fluid transport into brain and demonstrate altered morphology in aging and Alzheimer{\textquoteright}s disease",
abstract = "Perivascular spaces (PVS) drain brain waste metabolites, but their specific flow paths are debated. Meningeal pia mater reportedly forms the outermost boundary that confines flow around blood vessels. Yet, we show that pia is perforated and permissive to PVS fluid flow. Furthermore, we demonstrate that pia is comprised of vascular and cerebral layers that coalesce in variable patterns along leptomeningeal arteries, often merging around penetrating arterioles. Heterogeneous pial architectures form variable sieve-like structures that differentially influence cerebrospinal fluid (CSF) transport along PVS. The degree of pial coverage correlates with macrophage density and phagocytosis of CSF tracer. In vivo imaging confirms transpial influx of CSF tracer, suggesting a role of pia in CSF filtration, but not flow restriction. Additionally, pial layers atrophy with age. Old mice also exhibit areas of pial denudation that are not observed in young animals, but pia is unexpectedly hypertrophied in a mouse model of Alzheimer{\textquoteright}s disease. Moreover, pial thickness correlates with improved CSF flow and reduced β-amyloid deposits in PVS of old mice. We show that PVS morphology in mice is variable and that the structure and function of pia suggests a previously unrecognized role in regulating CSF transport and amyloid clearance in aging and disease.",
author = "Humberto Mestre and Natasha Verma and Greene, {Thom D.} and Lin, {Li Jing A.} and Antonio Ladron-de-Guevara and Sweeney, {Amanda M.} and Guojun Liu and Thomas, {V. Kaye} and Galloway, {Chad A.} and {de Mesy Bentley}, {Karen L.} and Maiken Nedergaard and Mehta, {Rupal I.}",
note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
doi = "10.1038/s41467-022-31257-9",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
number = "1",

}

RIS

TY - JOUR

T1 - Periarteriolar spaces modulate cerebrospinal fluid transport into brain and demonstrate altered morphology in aging and Alzheimer’s disease

AU - Mestre, Humberto

AU - Verma, Natasha

AU - Greene, Thom D.

AU - Lin, Li Jing A.

AU - Ladron-de-Guevara, Antonio

AU - Sweeney, Amanda M.

AU - Liu, Guojun

AU - Thomas, V. Kaye

AU - Galloway, Chad A.

AU - de Mesy Bentley, Karen L.

AU - Nedergaard, Maiken

AU - Mehta, Rupal I.

N1 - Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

N2 - Perivascular spaces (PVS) drain brain waste metabolites, but their specific flow paths are debated. Meningeal pia mater reportedly forms the outermost boundary that confines flow around blood vessels. Yet, we show that pia is perforated and permissive to PVS fluid flow. Furthermore, we demonstrate that pia is comprised of vascular and cerebral layers that coalesce in variable patterns along leptomeningeal arteries, often merging around penetrating arterioles. Heterogeneous pial architectures form variable sieve-like structures that differentially influence cerebrospinal fluid (CSF) transport along PVS. The degree of pial coverage correlates with macrophage density and phagocytosis of CSF tracer. In vivo imaging confirms transpial influx of CSF tracer, suggesting a role of pia in CSF filtration, but not flow restriction. Additionally, pial layers atrophy with age. Old mice also exhibit areas of pial denudation that are not observed in young animals, but pia is unexpectedly hypertrophied in a mouse model of Alzheimer’s disease. Moreover, pial thickness correlates with improved CSF flow and reduced β-amyloid deposits in PVS of old mice. We show that PVS morphology in mice is variable and that the structure and function of pia suggests a previously unrecognized role in regulating CSF transport and amyloid clearance in aging and disease.

AB - Perivascular spaces (PVS) drain brain waste metabolites, but their specific flow paths are debated. Meningeal pia mater reportedly forms the outermost boundary that confines flow around blood vessels. Yet, we show that pia is perforated and permissive to PVS fluid flow. Furthermore, we demonstrate that pia is comprised of vascular and cerebral layers that coalesce in variable patterns along leptomeningeal arteries, often merging around penetrating arterioles. Heterogeneous pial architectures form variable sieve-like structures that differentially influence cerebrospinal fluid (CSF) transport along PVS. The degree of pial coverage correlates with macrophage density and phagocytosis of CSF tracer. In vivo imaging confirms transpial influx of CSF tracer, suggesting a role of pia in CSF filtration, but not flow restriction. Additionally, pial layers atrophy with age. Old mice also exhibit areas of pial denudation that are not observed in young animals, but pia is unexpectedly hypertrophied in a mouse model of Alzheimer’s disease. Moreover, pial thickness correlates with improved CSF flow and reduced β-amyloid deposits in PVS of old mice. We show that PVS morphology in mice is variable and that the structure and function of pia suggests a previously unrecognized role in regulating CSF transport and amyloid clearance in aging and disease.

U2 - 10.1038/s41467-022-31257-9

DO - 10.1038/s41467-022-31257-9

M3 - Journal article

C2 - 35794106

AN - SCOPUS:85133558534

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 3897

ER -

ID: 314449358