A protective variant with lower synapse loss, but more plaques

The R522 variant of *PLCG2* lowers AD risk relative to the common P522 allele. R522 mice have more amyloid plaques when crossed to the *App^NL-G-F* AD mouse model line (c), yet experience less synapse loss as measured by the presynaptic marker Bassoon (d) and postsynaptic marker PSD-95 (e).

“Uncoupling of synaptic loss from amyloid burden by an Alzheimer’s disease protective variant of PLCγ2.”

Ryan J. Bevan, et al. – Cardiff University.

This study examined the effects of the rare protective R522 variant of Phospholipase C Gamma 2 (PLCG2) relative to the common P522. Despite experiencing less synaptic loss when crossed into the “Swedish, Iberian, Arctic” amyloid precursor protein knock-in (App^NL-G-F) AD model mouse line, R522 mice had more amyloid plaques that were also larger and more densely compacted. This disconnect suggests that synapse loss in Alzheimer’s may not necessarily be due to amyloid burden.

The impact of this study, however, is greatly reduced by the lack of behavioral or cognitive data. A demonstration that memory loss is curbed in R522 mice, despite the increased plaque burden, would do much more to question the link between amyloid burden and Alzheimer’s.