@article {320053, title = {Controversies about the subcellular localization and mechanisms of action of the Alzheimer{\textquoteright}s disease-protective CD33 splice variant.}, journal = {Acta Neuropathol}, year = {2019}, month = {Aug 22}, abstract = {

Genome-wide association studies (GWAS) identified an allele of the microglial CD33 (Siglec-3) cell surface receptor that protects against Alzheimer{\textquoteright}s disease (AD). Protected individuals express less full-length CD33 and more alternatively spliced D2-CD33 lacking the amino-terminal sialoglycan-ligand-binding domain. The mechanism by which D2-CD33 reduces AD risk is unknown. A recent excellent review [] concluded that the protective allele may act via gain of function, with excess cell surface D2-CD33 reducing risk via {\textquotedblleft}a higher propensity toward microglial activation through mechanisms similar to the well-recognized functions of TREM2 and its co-receptor, DAP12{\textquotedblright}. However, our earlier study [] showed that D2-CD33 (a.k.a. CD33m or CD33ΔV-Ig) is diverted to intracellular peroxisomes (consistent with a conserved peroxisomal targeting signal in the cytosolic tail).

}, isbn = {0001-6322}, doi = {https://doi.org/10.1007/s00401-019-02065-1}, url = {https://link.springer.com/article/10.1007\%2Fs00401-019-02065-1}, author = {Saha, S and Siddiqui, SS and Khan, N and Verhagen, A and Jiang, W and Springer, S and Ghosh, P and Ajit Varki} }