Increased TDP-43 expression by transgenic over-expression induces disease in animal models [49]; the relationship between expression level and disease is also apparent for genes linked to other diseases including α-synuclein (Parkinson’s disease, amyloid precursor protein (Alzheimer’s disease) and microtubule associated protein tau (frontotemporal dementia) [50]. This evidence concerns the gene TARDBP and early-onset autosomal dominant Alzheimer disease.