In addition, the T/A allele at rs3851179, located in the upstream region of PICALM, also provided a protective effect against AD, associated with increased Aβ clearance, lower ratios of CSF p/t-tau [57], and a slower rate of atrophy of the hippocampus [58]; however, the non-protective C allele in rs3851179 has been associated with early AOO of sporadic AD [58]. Here, PICALM is linked to Alzheimer disease.