De novo PSEN1 mutation (Pro436Gln) in a very early onset posterior variant of Alzheimer's disease is associated with pyramidal signs.

PSEN1 mutations should be considered in patients with sporadic very early onset dementia, as de novo mutations may occur. AD CSF biomarkers offer valuable diagnostic information in such cases. The specific mutation has a very strong impact in the clinical phenotype. Further, this case is another example that PSEN1 mutations affecting proline residues have the earliest age at onset.