This is a summary of an article by Mariel G Kozberg, Irvin Yi, Whitney M Freeze, Corinne A Auger, Ashley A Scherlek, Steven M Greenberg, Susanne J van Veluw which was published in Brain Communications, Volume 4, Issue 5, 2022, fcac245. It was published on 26 September 2022.
Here is a link to the complete article: https://doi.org/10.1093/braincomms/fcac245

Site editor’s note: Since this summary was prepared with assistance from ChatGPT, it may be missing key elements and there may be errors (although we have not found any).

This research article provides a detailed histopathological analysis of cases with Cerebral Amyloid Angiopathy (CAA) and offers the following key findings:

1. Vessel Grading and CAA-Related Effects: The study categorizes the brain’s blood vessels into different grades based on CAA pathology. Advanced grade vessels (Grades 3 and 4) consistently exhibit blood-brain barrier (BBB) leakage and perivascular inflammation. Grade 4 vessels, in particular, closely resemble vessels associated with Cerebral Microbleeds (CMBs) and lobar Intracerebral Hemorrhage (ICH), which suggests the CMBs and ICHs are most likely to occur in Grade 4 vessels – ti.e. those showing the highest levels of CAA.
2. Early Pathological Changes: The research reveals that even Grade 1 vessels, which only show patchy amyloid-beta (Aβ) deposition with otherwise normal vessel walls, exhibit significant changes such as BBB leakage and loss of contractile smooth muscle cells. These changes are observed from Grade 1 and continue through Grades 2, 3, and 4, with Grade 3 vessels displaying unique characteristics, including more contractile smooth muscle cell preservation and angiogenesis. (So Grade 3 vessels may be the result of a different CAA pathway).
3. Perivascular Inflammation: Perivascular inflammation primarily surrounds advanced grade vessels, especially Grade 4 vessels. This inflammation involves reactive astrocytes and activated microglia, with reactive astrocytes showing a stronger spatial relationship with the vessels studied.
4. Complex Relationship Between BBB Leakage and Inflammation: The interactions between BBB leakage and perivascular inflammation in CAA are bidirectional. Aβ is a known trigger for both local inflammation and BBB leakage. The study suggests that BBB leakage occurs earlier in CAA pathology than perivascular inflammation, implying that BBB leakage may contribute to inflammation in CAA.
5. Potential for Vessel Progression: The study indicates that Grade 2 vessel segments may progress directly to Grade 4. Interestingly, Grade 4 vessel segments have less Aβ within their walls than Grade 2 vessel segments, suggesting that inflammation may play a role in Aβ removal from vessel walls.

These findings suggest that BBB leakage and perivascular inflammation could be potential therapeutic targets for preventing hemorrhages in CAA.