Polymorphisms in the gene that encodes the transmembrane protein CD33 have previously been linked to Alzheimer's disease. Now, a new study shows that CD33 affects the ability of microglia to take up amyloid-β, the toxic peptide that accumulates in the brains of individuals with Alzheimer's disease (Neuron 78, 631–643).

Credit: Hybrid Medical / Science Source

Ana Griciuc et al. found that the CD33 allele that had previously been shown to protect humans against the disease results in reduced expression of the protein in human brain. When the researchers examined mouse models of the disease, they observed less brain accumulation of amyloid-β if the mice lacked CD33.

Griciuc et al. then showed that compared with brains from healthy people, CD33 expression was increased in microglia within the brains of individuals with Alzheimer's disease. When the authors overexpressed CD33 in microglia in cell culture, the cells were less able to take up amyloid-β from the culture medium compared with control microglia. These findings suggest that inhibition of CD33 could be a potential therapeutic approach to enhance microglial uptake of amyloid-β in Alzheimer's disease.