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Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
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Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry

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Effect of vascular amyloid on white matter disease is mediated by vascular dysfunction in cerebral amyloid angiopathy

Elif Gokcal1, Mitchell J Horn1, J Alex Becker2

  • 1Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
|January 28, 2022
PubMed

Insights

Vascular dysfunction mediates the link between amyloid in cerebral amyloid angiopathy (CAA) and white matter hyperintensities (WMH). Amyloid lowering therapies may prevent brain injury by targeting this vascular dysfunction.

Area of Science:

  • Neurology
  • Neuroimaging
  • Vascular Biology

Background:

  • Cerebral amyloid angiopathy (CAA) is associated with amyloid-beta deposition in cerebral vasculature.
  • White matter hyperintensities (WMH) are common in CAA and may result from vascular damage.
  • The relationship between amyloid load and WMH in CAA, and the role of vascular dysfunction, requires further elucidation.

Purpose of the Study:

  • To investigate whether vascular dysfunction mediates the association between amyloid load and WMH in cognitively healthy individuals with CAA.
  • To explore the role of amyloid burden (measured by PiB-PET) and vascular function (measured by fMRI) in the development of WMH.

Main Methods:

  • Structural MRI was used to quantify white matter hyperintensities (WMH) as percent of total intracranial volume (pWMH).
  • Positron Emission Tomography (PET) with Pittsburgh Compound B (PiB) measured global cortical amyloid load (PiB-DVR).
  • Functional MRI (fMRI) assessed vascular dysfunction using time-to-peak (TTP) of the blood oxygen-level-dependent response to visual stimulation.

Main Results:

  • Higher PiB-DVR (amyloid load) correlated with prolonged TTP (vascular dysfunction) and higher pWMH.
  • Prolonged TTP was independently associated with higher pWMH in multivariate regression.
  • Mediation analysis confirmed that TTP significantly mediated the relationship between PiB-DVR and pWMH.

Conclusions:

  • Vascular dysfunction, as indicated by prolonged TTP, plays a crucial role in mediating the association between amyloid load and white matter hyperintensities in CAA.
  • Amyloid-lowering strategies may prevent ischemic brain injury by improving vascular function and reducing WMH progression.
  • These findings highlight vascular dysfunction as a key therapeutic target in managing CAA-related brain pathology.
Keywords:
Amyloid angiopathycerebral autoregulationcerebrovascular diseasemolecular imagingpositron emission tomographywhite matter disease

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