As the disease progresses, plaque clusters made of a misfolded protein called "a-beta" accumulate in areas of the brain that control memory, mood and spatial awareness.
Taken together, our results demonstrate the clustering of plaques and the subsequent merger of plaque clusters as a mechanism of large plaque formation.
As shown in a representative comparison in Fig. 4, many of the plaque clusters (white numbers) were readily visualized in the corresponding MR image as distinct signal voids.
A first hint for plaque clustering came from computer simulations of plaque deposition, demonstrating that a mere random process could not account for the plaque deposition pattern observed in post-mortem brain sections.
With long-term in vivo imaging over 5.5 months, we witnessed the fusion of dense core plaque clusters into a larger core, confirming our finding with a different technique (Fig. 6a g).
Glial fibrillary acidic protein immunoreactivity was higher in cortical regions in comparison to non-cortical regions and reactive astrocytes were observed in areas with large amounts of amyloid plaque clusters (Fig. 6F).
These clusters of newly developed plaques suggest that once a new plaque has formed, subsequent new plaques cluster in the vicinity of this original new plaque.
There is evidence that plaques can grow uniformly over time; however, a complementary hypothesis of plaque development is that small plaques cluster and grow together thereby forming larger plaques.
Furthermore, large plaques can contain multiple pre-existing dense cores that can fuse over time supporting the novel hypothesis that multiple, individually small plaques cluster to ultimately build a larger plaque (Fig. 7).
However, coexisting with and outside of these inflammatory plaques, clusters of infected astrocytes are found, thus showing continuing viral spread despite an effective intrathecal anti-viral immune response [ 39].
