Mice Carrying Unmutated Human SIGLEC10 Gene Cluster Transgene Develop Both Amyloid Plaques and Tau Neurofilament Tangles: A Model for Late Onset Alzheimer’s Disease

Mice with transgenic expression of unmutated human SIGLEC10 gene cluster in microglia presented with marked increase of both NTF and Aβ plaques at 9 to 13 months. Short-term 4-week anti-Siglec10 treatment significantly reduced both NTF and Aβ plaques in transgenic mice. These data demonstrate a causal relationship between SIGLEC10 and pathogenesis of late onset AD which is not associated with pathogenic mutations in early onset AD, such as APOE4, APP, PS1, PS2 or MAPT. To our knowledge, this is the first mouse model in which a single un-mutated human gene cluster exacerbate both pTau aggregates and Aβ plaques, two critical AD hallmarks.