Each has a distinct clinical, pathological and biochemical signature, including the accumulation of disease-specific misfolded protein/s in the brain: amyloid-β and hyperphosphorylated tau in Alzheimer’s disease, α-synuclein in Parkinson’s disease, TDP-43 (TARDBP), FUS or SOD1 in ALS and prion protein (PrP, encoded by PRNP) in prion diseases. Here, PRNP is linked to early-onset autosomal dominant Alzheimer disease.