Vascular dysfunction—The disregarded partner of Alzheimer's disease

Melanie D. Sweeney; Axel Montagne; Abhay P. Sagare; Daniel A. Nation; Lon S. Schneider; Helena C. Chui; Michael G. Harrington; Judy Pa; Meng Law; Danny J.J. Wang; Russell E. Jacobs; Fergus N. Doubal; Joel Ramirez; Sandra E. Black; Maiken Nedergaard; Helene Benveniste; Martin Dichgans; Costantino Iadecola; Seth Love; Philip M. Bath; Hugh S. Markus; Rustam A. Salman; Stuart M. Allan; Terence J. Quinn; Rajesh N. Kalaria; David J. Werring; Roxana O. Carare; Rhian M. Touyz; Steve C.R. Williams; Michael A. Moskowitz; Zvonimir S. Katusic; Sarah E. Lutz; Orly Lazarov; Richard D. Minshall; Jalees Rehman; Thomas P. Davis; Cheryl L. Wellington; Hector M. González; Chun Yuan; Samuel N. Lockhart; Timothy M. Hughes; Christopher L.H. Chen; Perminder Sachdev; John T. O'Brien; Ingmar Skoog; Leonardo Pantoni; Deborah R. Gustafson; Geert Jan Biessels; Anders Wallin; Eric E. Smith; Vincent Mok; Adrian Wong; Peter Passmore; Frederick Barkof; Majon Muller; Monique M.B. Breteler; Gustavo C. Román; Edith Hamel; Sudha Seshadri; Rebecca F. Gottesman; Mark A. van Buchem; Zoe Arvanitakis; Julie A. Schneider; Lester R. Drewes; Vladimir Hachinski; Caleb E. Finch; Arthur W. Toga; Joanna M. Wardlaw; Berislav V. Zlokovic

doi:10.1016/j.jalz.2018.07.222

Vascular dysfunction—The disregarded partner of Alzheimer's disease

Melanie D. Sweeney, Axel Montagne, Abhay P. Sagare, Daniel A. Nation, Lon S. Schneider, Helena C. Chui, Michael G. Harrington, Judy Pa, Meng Law, Danny J.J. Wang, Russell E. Jacobs, Fergus N. Doubal, Joel Ramirez, Sandra E. Black, Maiken Nedergaard, Helene Benveniste, Martin Dichgans, Costantino Iadecola, Seth Love, Philip M. BathHugh S. Markus, Rustam A. Salman, Stuart M. Allan, Terence J. Quinn, Rajesh N. Kalaria, David J. Werring, Roxana O. Carare, Rhian M. Touyz, Steve C.R. Williams, Michael A. Moskowitz, Zvonimir S. Katusic, Sarah E. Lutz, Orly Lazarov, Richard D. Minshall, Jalees Rehman, Thomas P. Davis, Cheryl L. Wellington, Hector M. González, Chun Yuan, Samuel N. Lockhart, Timothy M. Hughes, Christopher L.H. Chen, Perminder Sachdev, John T. O'Brien, Ingmar Skoog, Leonardo Pantoni, Deborah R. Gustafson, Geert Jan Biessels, Anders Wallin, Eric E. Smith, Vincent Mok, Adrian Wong, Peter Passmore, Frederick Barkof, Majon Muller, Monique M.B. Breteler, Gustavo C. Román, Edith Hamel, Sudha Seshadri, Rebecca F. Gottesman, Mark A. van Buchem, Zoe Arvanitakis, Julie A. Schneider, Lester R. Drewes, Vladimir Hachinski, Caleb E. Finch, Arthur W. Toga, Joanna M. Wardlaw, Berislav V. Zlokovic

Biomedical Sciences

Research output: Contribution to journal › Short survey › peer-review

347 Scopus citations

Abstract

Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging–Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts.

Original language	English (US)
Pages (from-to)	158-167
Number of pages	10
Journal	Alzheimer's and Dementia
Volume	15
Issue number	1
DOIs	https://doi.org/10.1016/j.jalz.2018.07.222
State	Published - Jan 2019

Bibliographical note

Funding Information:
Supported by the National Institutes of Health (NIH) grants R01AG023084 (B.V.Z.), R01NS090904 (B.V.Z.), R01NS034467 (B.V.Z.), R01AG039452 (B.V.Z.), 1R01NS100459 (B.V.Z.), 5P01AG052350 (B.V.Z.), 5P50AG005142 (H.C.C.; University of Southern California Alzheimer's Disease Research Center), EB015922 (A.W.T.; Laboratory of Neuro Imaging , LONI), R37-NS089323 (C.I.), R01-NS100447 (C.I.), R01-NS09544 (C.I.), R01-NS/HL037853 (C.I.), R01-NS034179 (C.I.), KL2-TR002002 (S.E.L.), R01-AG064248 (H.M.G.), RF1-AG054548 (H.M.G.), P30-AG005131 (H.M.G.), R21-AG056952 (H.M.G.), P30AG049638 (T.M.H.; S.N.L), R01AG054069 (T.M.H.; S.N.L.), R01HL096814 (T.M.H.), and R01AG053938 (T.M.H.) in addition to the Alzheimer's Association , Cure Alzheimer's Fund , and the Foundation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease reference no. 16 CVD 05.

Funding Information:
Supported by the National Institutes of Health (NIH) grants R01AG023084 (B.V.Z.), R01NS090904 (B.V.Z.), R01NS034467 (B.V.Z.), R01AG039452 (B.V.Z.), 1R01NS100459 (B.V.Z.), 5P01AG052350 (B.V.Z.), 5P50AG005142 (H.C.C.; University of Southern California Alzheimer's Disease Research Center), EB015922 (A.W.T.; Laboratory of Neuro Imaging, LONI), R37-NS089323 (C.I.), R01-NS100447 (C.I.), R01-NS09544 (C.I.), R01-NS/HL037853 (C.I.), R01-NS034179 (C.I.), KL2-TR002002 (S.E.L.), R01-AG064248 (H.M.G.), RF1-AG054548 (H.M.G.), P30-AG005131 (H.M.G.), R21-AG056952 (H.M.G.), P30AG049638 (T.M.H.; S.N.L), R01AG054069 (T.M.H.; S.N.L.), R01HL096814 (T.M.H.), and R01AG053938 (T.M.H.) in addition to the Alzheimer's Association, Cure Alzheimer's Fund, and the Foundation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease reference no. 16 CVD 05.

Publisher Copyright:
© 2018 the Alzheimer's Association

Keywords

Alzheimer's disease
Biomarkers
Blood-brain barrier
Cerebral blood flow
MRI
Vascular

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1016/j.jalz.2018.07.222

Find It

Find It at U of M Libraries

Cite this

Sweeney, M. D., Montagne, A., Sagare, A. P., Nation, D. A., Schneider, L. S., Chui, H. C., Harrington, M. G., Pa, J., Law, M., Wang, D. J. J., Jacobs, R. E., Doubal, F. N., Ramirez, J., Black, S. E., Nedergaard, M., Benveniste, H., Dichgans, M., Iadecola, C., Love, S., ... Zlokovic, B. V. (2019). Vascular dysfunction—The disregarded partner of Alzheimer's disease. Alzheimer's and Dementia, 15(1), 158-167. https://doi.org/10.1016/j.jalz.2018.07.222

Sweeney, MD, Montagne, A, Sagare, AP, Nation, DA, Schneider, LS, Chui, HC, Harrington, MG, Pa, J, Law, M, Wang, DJJ, Jacobs, RE, Doubal, FN, Ramirez, J, Black, SE, Nedergaard, M, Benveniste, H, Dichgans, M, Iadecola, C, Love, S, Bath, PM, Markus, HS, Salman, RA, Allan, SM, Quinn, TJ, Kalaria, RN, Werring, DJ, Carare, RO, Touyz, RM, Williams, SCR, Moskowitz, MA, Katusic, ZS, Lutz, SE, Lazarov, O, Minshall, RD, Rehman, J, Davis, TP, Wellington, CL, González, HM, Yuan, C, Lockhart, SN, Hughes, TM, Chen, CLH, Sachdev, P, O'Brien, JT, Skoog, I, Pantoni, L, Gustafson, DR, Biessels, GJ, Wallin, A, Smith, EE, Mok, V, Wong, A, Passmore, P, Barkof, F, Muller, M, Breteler, MMB, Román, GC, Hamel, E, Seshadri, S, Gottesman, RF, van Buchem, MA, Arvanitakis, Z, Schneider, JA, Drewes, LR, Hachinski, V, Finch, CE, Toga, AW, Wardlaw, JM & Zlokovic, BV 2019, 'Vascular dysfunction—The disregarded partner of Alzheimer's disease', Alzheimer's and Dementia, vol. 15, no. 1, pp. 158-167. https://doi.org/10.1016/j.jalz.2018.07.222

@article{b1d6ca7c97e0407e88ee796380fe89b9,

title = "Vascular dysfunction—The disregarded partner of Alzheimer's disease",

abstract = "Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging–Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts.",

keywords = "Alzheimer's disease, Biomarkers, Blood-brain barrier, Cerebral blood flow, MRI, Vascular",

author = "Sweeney, {Melanie D.} and Axel Montagne and Sagare, {Abhay P.} and Nation, {Daniel A.} and Schneider, {Lon S.} and Chui, {Helena C.} and Harrington, {Michael G.} and Judy Pa and Meng Law and Wang, {Danny J.J.} and Jacobs, {Russell E.} and Doubal, {Fergus N.} and Joel Ramirez and Black, {Sandra E.} and Maiken Nedergaard and Helene Benveniste and Martin Dichgans and Costantino Iadecola and Seth Love and Bath, {Philip M.} and Markus, {Hugh S.} and Salman, {Rustam A.} and Allan, {Stuart M.} and Quinn, {Terence J.} and Kalaria, {Rajesh N.} and Werring, {David J.} and Carare, {Roxana O.} and Touyz, {Rhian M.} and Williams, {Steve C.R.} and Moskowitz, {Michael A.} and Katusic, {Zvonimir S.} and Lutz, {Sarah E.} and Orly Lazarov and Minshall, {Richard D.} and Jalees Rehman and Davis, {Thomas P.} and Wellington, {Cheryl L.} and Gonz{\'a}lez, {Hector M.} and Chun Yuan and Lockhart, {Samuel N.} and Hughes, {Timothy M.} and Chen, {Christopher L.H.} and Perminder Sachdev and O'Brien, {John T.} and Ingmar Skoog and Leonardo Pantoni and Gustafson, {Deborah R.} and Biessels, {Geert Jan} and Anders Wallin and Smith, {Eric E.} and Vincent Mok and Adrian Wong and Peter Passmore and Frederick Barkof and Majon Muller and Breteler, {Monique M.B.} and Rom{\'a}n, {Gustavo C.} and Edith Hamel and Sudha Seshadri and Gottesman, {Rebecca F.} and {van Buchem}, {Mark A.} and Zoe Arvanitakis and Schneider, {Julie A.} and Drewes, {Lester R.} and Vladimir Hachinski and Finch, {Caleb E.} and Toga, {Arthur W.} and Wardlaw, {Joanna M.} and Zlokovic, {Berislav V.}",

note = "Funding Information: Supported by the National Institutes of Health (NIH) grants R01AG023084 (B.V.Z.), R01NS090904 (B.V.Z.), R01NS034467 (B.V.Z.), R01AG039452 (B.V.Z.), 1R01NS100459 (B.V.Z.), 5P01AG052350 (B.V.Z.), 5P50AG005142 (H.C.C.; University of Southern California Alzheimer's Disease Research Center), EB015922 (A.W.T.; Laboratory of Neuro Imaging , LONI), R37-NS089323 (C.I.), R01-NS100447 (C.I.), R01-NS09544 (C.I.), R01-NS/HL037853 (C.I.), R01-NS034179 (C.I.), KL2-TR002002 (S.E.L.), R01-AG064248 (H.M.G.), RF1-AG054548 (H.M.G.), P30-AG005131 (H.M.G.), R21-AG056952 (H.M.G.), P30AG049638 (T.M.H.; S.N.L), R01AG054069 (T.M.H.; S.N.L.), R01HL096814 (T.M.H.), and R01AG053938 (T.M.H.) in addition to the Alzheimer's Association , Cure Alzheimer's Fund , and the Foundation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease reference no. 16 CVD 05. Funding Information: Supported by the National Institutes of Health (NIH) grants R01AG023084 (B.V.Z.), R01NS090904 (B.V.Z.), R01NS034467 (B.V.Z.), R01AG039452 (B.V.Z.), 1R01NS100459 (B.V.Z.), 5P01AG052350 (B.V.Z.), 5P50AG005142 (H.C.C.; University of Southern California Alzheimer's Disease Research Center), EB015922 (A.W.T.; Laboratory of Neuro Imaging, LONI), R37-NS089323 (C.I.), R01-NS100447 (C.I.), R01-NS09544 (C.I.), R01-NS/HL037853 (C.I.), R01-NS034179 (C.I.), KL2-TR002002 (S.E.L.), R01-AG064248 (H.M.G.), RF1-AG054548 (H.M.G.), P30-AG005131 (H.M.G.), R21-AG056952 (H.M.G.), P30AG049638 (T.M.H.; S.N.L), R01AG054069 (T.M.H.; S.N.L.), R01HL096814 (T.M.H.), and R01AG053938 (T.M.H.) in addition to the Alzheimer's Association, Cure Alzheimer's Fund, and the Foundation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease reference no. 16 CVD 05. Publisher Copyright: {\textcopyright} 2018 the Alzheimer's Association",

year = "2019",

month = jan,

doi = "10.1016/j.jalz.2018.07.222",

language = "English (US)",

volume = "15",

pages = "158--167",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Elsevier Inc.",

number = "1",

}

TY - JOUR

T1 - Vascular dysfunction—The disregarded partner of Alzheimer's disease

AU - Sweeney, Melanie D.

AU - Montagne, Axel

AU - Sagare, Abhay P.

AU - Nation, Daniel A.

AU - Schneider, Lon S.

AU - Chui, Helena C.

AU - Harrington, Michael G.

AU - Pa, Judy

AU - Law, Meng

AU - Wang, Danny J.J.

AU - Jacobs, Russell E.

AU - Doubal, Fergus N.

AU - Ramirez, Joel

AU - Black, Sandra E.

AU - Nedergaard, Maiken

AU - Benveniste, Helene

AU - Dichgans, Martin

AU - Iadecola, Costantino

AU - Love, Seth

AU - Bath, Philip M.

AU - Markus, Hugh S.

AU - Salman, Rustam A.

AU - Allan, Stuart M.

AU - Quinn, Terence J.

AU - Kalaria, Rajesh N.

AU - Werring, David J.

AU - Carare, Roxana O.

AU - Touyz, Rhian M.

AU - Williams, Steve C.R.

AU - Moskowitz, Michael A.

AU - Katusic, Zvonimir S.

AU - Lutz, Sarah E.

AU - Lazarov, Orly

AU - Minshall, Richard D.

AU - Rehman, Jalees

AU - Davis, Thomas P.

AU - Wellington, Cheryl L.

AU - González, Hector M.

AU - Yuan, Chun

AU - Lockhart, Samuel N.

AU - Hughes, Timothy M.

AU - Chen, Christopher L.H.

AU - Sachdev, Perminder

AU - O'Brien, John T.

AU - Skoog, Ingmar

AU - Pantoni, Leonardo

AU - Gustafson, Deborah R.

AU - Biessels, Geert Jan

AU - Wallin, Anders

AU - Smith, Eric E.

AU - Mok, Vincent

AU - Wong, Adrian

AU - Passmore, Peter

AU - Barkof, Frederick

AU - Muller, Majon

AU - Breteler, Monique M.B.

AU - Román, Gustavo C.

AU - Hamel, Edith

AU - Seshadri, Sudha

AU - Gottesman, Rebecca F.

AU - van Buchem, Mark A.

AU - Arvanitakis, Zoe

AU - Schneider, Julie A.

AU - Drewes, Lester R.

AU - Hachinski, Vladimir

AU - Finch, Caleb E.

AU - Toga, Arthur W.

AU - Wardlaw, Joanna M.

AU - Zlokovic, Berislav V.

N1 - Funding Information: Supported by the National Institutes of Health (NIH) grants R01AG023084 (B.V.Z.), R01NS090904 (B.V.Z.), R01NS034467 (B.V.Z.), R01AG039452 (B.V.Z.), 1R01NS100459 (B.V.Z.), 5P01AG052350 (B.V.Z.), 5P50AG005142 (H.C.C.; University of Southern California Alzheimer's Disease Research Center), EB015922 (A.W.T.; Laboratory of Neuro Imaging , LONI), R37-NS089323 (C.I.), R01-NS100447 (C.I.), R01-NS09544 (C.I.), R01-NS/HL037853 (C.I.), R01-NS034179 (C.I.), KL2-TR002002 (S.E.L.), R01-AG064248 (H.M.G.), RF1-AG054548 (H.M.G.), P30-AG005131 (H.M.G.), R21-AG056952 (H.M.G.), P30AG049638 (T.M.H.; S.N.L), R01AG054069 (T.M.H.; S.N.L.), R01HL096814 (T.M.H.), and R01AG053938 (T.M.H.) in addition to the Alzheimer's Association , Cure Alzheimer's Fund , and the Foundation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease reference no. 16 CVD 05. Funding Information: Supported by the National Institutes of Health (NIH) grants R01AG023084 (B.V.Z.), R01NS090904 (B.V.Z.), R01NS034467 (B.V.Z.), R01AG039452 (B.V.Z.), 1R01NS100459 (B.V.Z.), 5P01AG052350 (B.V.Z.), 5P50AG005142 (H.C.C.; University of Southern California Alzheimer's Disease Research Center), EB015922 (A.W.T.; Laboratory of Neuro Imaging, LONI), R37-NS089323 (C.I.), R01-NS100447 (C.I.), R01-NS09544 (C.I.), R01-NS/HL037853 (C.I.), R01-NS034179 (C.I.), KL2-TR002002 (S.E.L.), R01-AG064248 (H.M.G.), RF1-AG054548 (H.M.G.), P30-AG005131 (H.M.G.), R21-AG056952 (H.M.G.), P30AG049638 (T.M.H.; S.N.L), R01AG054069 (T.M.H.; S.N.L.), R01HL096814 (T.M.H.), and R01AG053938 (T.M.H.) in addition to the Alzheimer's Association, Cure Alzheimer's Fund, and the Foundation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease reference no. 16 CVD 05. Publisher Copyright: © 2018 the Alzheimer's Association

PY - 2019/1

Y1 - 2019/1

N2 - Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging–Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts.

AB - Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging–Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts.

KW - Alzheimer's disease

KW - Biomarkers

KW - Blood-brain barrier

KW - Cerebral blood flow

KW - MRI

KW - Vascular

UR - http://www.scopus.com/inward/record.url?scp=85059512191&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059512191&partnerID=8YFLogxK

U2 - 10.1016/j.jalz.2018.07.222

DO - 10.1016/j.jalz.2018.07.222

M3 - Short survey

C2 - 30642436

AN - SCOPUS:85059512191

SN - 1552-5260

VL - 15

SP - 158

EP - 167

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 1

ER -

Vascular dysfunction—The disregarded partner of Alzheimer's disease

Abstract

Bibliographical note

Keywords

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this