Anti-MS4A6A monoclonal antibody Made to order

CD20, the high-affinity IgE receptor beta chain (Fc epsilon RI beta), and HTm4 are structurally related cell surface proteins expressed by hematopoietic cells. Recently, 16 novel human and mouse genes were identified that encode new members of this nascent protein family that we have named the membrane-spanning 4A gene family, with at least 12 subgroups (MS4A1-MS4A12). In the current study, we identified three additional human MS4A genes: MS4A4E, MS4A6E, and MS4A10. All family members have at least four potential transmembrane domains and N- and C-terminal cytoplasmic domains encoded by distinct exons, except MS4A6E which contains two transmembrane domains. Otherwise, the 12 currently identified MS4A genes share common structural features and similar intron/exon splice boundaries, and are clustered along an similar to 600-kb region of Chromosome 11q12. In contrast to other MS4A genes, MS4A4E, MS4A6E, and MS4A10 transcripts were rare and not detected among hematopoietic cells and most nonlymphoid tissues. Sequence polymorphisms were identified in the MS4A6E gene and common splice variants were observed for the MS4A4A, MS4A5, MS4A6A, and MS4A7 genes. Thus, the MS4A family currently includes 24 distinct human and mouse genes. Like CD20 and Fc epsilon RI beta, the 10 other human MS4A family members are likely to be components of oligomeric cell surface complexes involved in signal transduction in diverse cell lineages.

Objective: We investigated the association between apoE protein plasma levels and brain amyloidosis and the effect of the top 10 Alzheimer disease (AD) risk genes on this association. Methods: Our dataset consisted of 18 AD, 52 mild cognitive impairment, and 3 cognitively normal Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) participants with available [C-11]-Pittsburgh compound B (PiB) and peripheral blood protein data. We used cortical pattern matching to study associations between plasma apoE and cortical PiB binding and the effect of carrier status for the top 10 AD risk genes. Results: Low plasma apoE was significantly associated with high PiB SUVR, except in the sensorimotor and entorhinal cortex. For BIN1 rs744373, the association was observed only in minor allele carriers. For CD2AP rs9349407 and CR1 rs3818361, the association was preserved only in minor allele noncarriers. We did not find evidence for modulation by CLU, PICALM, ABCA7, BIN1, and MS4A6A. Conclusions: Our data show that BIN1 rs744373, CD2AP rs9349407, and CR1 rs3818361 genotypes modulate the association between apoE protein plasma levels and brain amyloidosis, implying a potential epigenetic/downstream interaction.