Basic Science and Pathogenesis

Area of Science:

• Neuroscience
• Ophthalmology
• Pathology

Background:

• Cerebrospinal fluid (CSF) and interstitial fluid are cleared from the brain via pathways including Intramural Periarterial Drainage (IPAD).
• Cerebral amyloid angiopathy (CAA) is linked to impaired IPAD of amyloid-beta (Abeta) in brain vasculature.
• Abeta deposition patterns suggest retinal arteries may also utilize IPAD for solute elimination.

Purpose of the Study:

• To investigate the presence and pathways of Abeta deposition in the retina and cribriform plate in patients with CAA.
• To determine if retinal Intramural Periarterial Drainage (IPAD) is affected in cerebral amyloid angiopathy (CAA).

Main Methods:

• Analysis of cadaveric retinae from patients with CAA for Abeta presence.
• Examination of cadaveric cribriform plates for leptomeninges along foramina.
• Immunohistochemical staining for Abeta and epithelial membrane antigen.

Main Results:

• Abeta was identified within the basement membranes of retinal artery smooth muscle cells.
• Epithelial membrane antigen, a marker for leptomeninges (arachnoid), was found lining the cribriform plate foramina.
• Findings indicate Abeta deposition in retinal IPAD pathways and the presence of arachnoid lining cribriform plate foramina.

Conclusions:

• Failure of Intramural Periarterial Drainage (IPAD) in the brain parenchyma in CAA is associated with a concurrent failure of retinal IPAD.
• The arachnoid lining the cribriform plate foramina provides a drainage pathway from the subarachnoid space into the nasal cavity.
• These findings highlight a potential dual role of IPAD failure in both the brain and retina in the pathogenesis of CAA.