While PGRN is a secreted protein that can be readily detected in plasma, it is somewhat surprising that TDP-43, a predominantly nuclear protein, is also detectable in plasma with ELISA [85]; raised levels of TDP-43 were detected in 46% of FTLD patients, 22% of Alzheimer’s disease and 8% of controls. This evidence concerns the gene GRN and early-onset autosomal dominant Alzheimer disease.