Why increased CSF t-tau and p-tau are specific to AD can be explained by considering that (1) the pattern of tau phosphorylation occurring in these disorders is disease-specific, (2) tangle pathology and neurodegeneration in AD may be consequent to Aβ accumulation, with disease-specific molecular cascades, such as kinases and proteases activation, (3) disease-specific tau truncation could prevent detection by currently available assays, and (4) specific pathological changes can be more severe in AD than in other tauopathies. The gene discussed is MAPT; the disease is Alzheimer disease.