The researchers investigated the CD33 gene, which encodes a protein (CD33) that’s involved in various types of cell-cell interactions. Although CD33 has several functions, it wasn’t previously known to do anything within the brain. Griciuc and her colleagues have now found that not only is CD33 expressed in microglial cells (the brain’s resident immune system cells) but that the amount of CD33 in the brain correlates with the number of Aβ plaques. AD patients have nearly 50% more CD33-producing microglial cells than healthy people and each of their microglial cells makes more CD33.
So AD patients have more CD33 protein and more Aβ plaques. What’s going on? To find out, the scientists looked at some mutant versions of the CD33 gene.
Like most genes, CD33 comes in different flavors, or alleles. One in particular encodes a defective form of the CD33 protein. The researchers were able to breed mice that had only this mutant version of the CD33 gene. When Aβ was added to microglial cells from the brains of the mutant mice it was absorbed by those mutant microglia. In contrast, normal microglial cells did not absorb Aβ.
What seems to be going on is that the microglial cells within the brain are churning out CD33. If the cells make normal functioning CD33, then those microglial cells can’t remove Aβ from the brain. If, on the other hand, the cells make defective CD33, then Aβ can be vacuumed out by the microglia. The production of CD33 somehow inhibits the uptake of Aβ by the microglial cells.
If you’re thinking that targeting CD33 might be a promising tactic for an AD cure, you’re not alone. The authors suggest sending in anti-CD33 antibodies to clear out the CD33. Alternatively, since CD33 is known to bind to sialic acid, it might be possible to throw in some extra sialic acid to keep down the levels of free CD33. Even though we’re clearly a long way away from even starting clinical trials, I find these possibilities heartening.