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Updated: Aug 1, 2025
Visualization of Amyloid β Deposits in the Human Brain with Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry
Published on: March 7, 2019
Pathogenesis of cerebral amyloid angiopathy caused by chaotic glymphatics-Mini-review
Forshing Lui1, Jessa Alcaide1, Stella Knowlton1
1Department of Clinical Sciences, California Northstate University College of Medicine, Elk Grove, CA, United States.
Insights
Cerebral amyloid angiopathy (CAA) involves amyloid beta (Aβ) deposition in brain arteries. This study proposes a retrograde transport mechanism for Aβ, potentially linked to glymphatic system disturbances, to explain CAA pathogenesis.
Area of Science:
- Neurology
- Pathology
- Neuroscience
Background:
- Cerebral amyloid angiopathy (CAA) is a significant cause of intracerebral hemorrhage in older adults.
- CAA shares amyloid beta (Aβ) deposition pathology with Alzheimer's disease (AD), but Aβ localization differs (vascular walls in CAA vs. neurites in AD).
- The precise mechanism of Aβ deposition in cerebral arterial walls in CAA remains poorly understood.
Purpose of the Study:
- To investigate the pathogenesis of cerebral amyloid angiopathy (CAA).
- To elucidate the mechanism of amyloid beta (Aβ) fibril deposition in cerebral and meningeal arterial walls.
- To explore the potential role of glymphatic system dysfunction in CAA.
Main Methods:
- Case study of aneurysmal subarachnoid hemorrhage followed by localized CAA.
- Review of amyloid beta (Aβ) formation and transport pathways.
- Postulation of a retrograde transport mechanism for Aβ in CAA.
Main Results:
- An unusual case presented with subarachnoid hemorrhage followed by localized CAA.
- A hypothesis for retrograde Aβ transport from brain parenchyma to arterial walls was proposed.
- Disturbances in the glymphatic system, aquaporin-4 channels, and parenchymal border macrophages were noted.
Conclusions:
- The study proposes a novel retrograde transport mechanism for amyloid beta (Aβ) in the pathogenesis of cerebral amyloid angiopathy (CAA).
- Glymphatic system dysfunction and associated cellular components may play a critical role in CAA development.
- Further research is warranted to validate the proposed Aβ transport pathway and its clinical implications.
Abstract:
Cerebral amyloid angiopathy (CAA) is a common cause of lobar intracerebral hemorrhage in the elderly. It is also associated pathologically with Alzheimer's disease (AD). Both CAA and AD share similar pathology of deposition amyloid beta fibrils (Aβ). Aβ is deposited mainly in the neurites in AD and vascular walls in CAA. Aβ is formed inside the brain parenchyma from the amyloid precursor protein. It is easier to understand how Aβ is deposited in the cerebral neurites in AD. However, the pathogenesis of CAA is still largely unknown. It is difficult to understand or visualize how Aβ fibrils formed inside the brain can be deposited against the cerebral perfusion pressure to be deposited in the cerebral and meningeal arterial walls. We encountered an unusual clinical case of acute aneurysmal subarachnoid hemorrhage which was followed after a few years with localized CAA involving mainly the sites of the subarachnoid hemorrhage. We reviewed the formation of Aβ and postulated how the Aβ fibrils are transported retrogradely toward the cerebral arteries and deposited in the arterial walls resulting in the final pathology of CAA. There is a clear disturbance of the glymphatic system, the aquaporin-4 channel, and the parenchymal border macrophages.
