In this context it is important to note that while tau and Aβ40 and 42 proteins are also produced outside the CNS, they mostly originate from the brain, and plasma levels have been shown to reflect both cerebrospinal levels [47] and brain load as assessed by proton-emission tomography (PET) [48,49,50], and to significantly differ in the pre-clinical AD stages, although less consistently in the more advanced stages of the disease [51,52,53]. The gene discussed is MAPT; the disease is Alzheimer disease.