Acta Neuropathologica

, Volume 131, Issue 5, pp 687–707 | Cite as

Brain imaging of neurovascular dysfunction in Alzheimer’s disease

  • Axel Montagne
  • Daniel A. Nation
  • Judy Pa
  • Melanie D. Sweeney
  • Arthur W. Toga
  • Berislav V. ZlokovicEmail author


Neurovascular dysfunction, including blood–brain barrier (BBB) breakdown and cerebral blood flow (CBF) dysregulation and reduction, are increasingly recognized to contribute to Alzheimer’s disease (AD). The spatial and temporal relationships between different pathophysiological events during preclinical stages of AD, including cerebrovascular dysfunction and pathology, amyloid and tau pathology, and brain structural and functional changes remain, however, still unclear. Recent advances in neuroimaging techniques, i.e., magnetic resonance imaging (MRI) and positron emission tomography (PET), offer new possibilities to understand how the human brain works in health and disease. This includes methods to detect subtle regional changes in the cerebrovascular system integrity. Here, we focus on the neurovascular imaging techniques to evaluate regional BBB permeability (dynamic contrast-enhanced MRI), regional CBF changes (arterial spin labeling- and functional-MRI), vascular pathology (structural MRI), and cerebral metabolism (PET) in the living human brain, and examine how they can inform about neurovascular dysfunction and vascular pathophysiology in dementia and AD. Altogether, these neuroimaging approaches will continue to elucidate the spatio-temporal progression of vascular and neurodegenerative processes in dementia and AD and how they relate to each other.


Alzheimer’s disease Neurovascular dysfunction Blood–brain barrier Cerebral blood flow Magnetic resonance imaging 



Alzheimer’s disease


Arterial input function


Apolipoprotein E


Albumin ratio


Arterial spin labeling

Amyloid beta


Blood–brain barrier


Blood oxygen level-dependent


Cornu ammonis 1


Cerebral amyloid angiopathy


Cerebral blood flow


Cerebral blood volume


Cerebral microbleed


Cerebral metabolic rate of glucose


Cerebral metabolic rate of oxygen consumption


Cerebrospinal fluid


Dynamic contrast-enhanced




Default mode network


Dementia rating scale


Diffusion tensor imaging


Fractional anisotropy




Fluid-attenuated inversion recovery


Functional magnetic resonance imaging


Gadolinium-based contrast agent






Mild cognitive impairment


Mean diffusivity


Magnetic resonance imaging


No cognitive impairment


Neurovascular unit


Positron emission tomography


Pittsburgh compound B




Signal-to-noise ratio


Soluble platelet-derived growth factor receptor-β


Susceptibility weighted imaging




White matter


White matter hyperintensity


White matter lesion



We thank the National Institutes of Health (NIH), the Zilkha Senior Scholar program, and the Alzheimer’s Association for support. Dr. Zlokovic’s research is supported by the NIH through grants R37NS34467, R37AG23084, and R01AG039452. Dr. Pa’s research is supported by the NIH through grant R01AG046928 and the Alzheimer’s Association grant NIRP12259277. Dr. Toga’s research is supported by the NIH through grant P41EB015922. We apologize to those authors whose original work we were not able to cite due to the limited length of this review.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Axel Montagne
    • 1
  • Daniel A. Nation
    • 2
  • Judy Pa
    • 3
  • Melanie D. Sweeney
    • 1
  • Arthur W. Toga
    • 3
  • Berislav V. Zlokovic
    • 1
    Email author
  1. 1.Zilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  2. 2.Department of PsychologyUniversity of Southern CaliforniaLos AngelesUSA
  3. 3.Department of Neurology, Institute for Neuroimaging and InformaticsUniversity of Southern CaliforniaLos AngelesUSA

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