Background: Presenilin-1 (PSEN-1) is a component of the γ-secretase complex involved in
β-amyloid Precursor Protein (AβPP) processing. Usually, Alzheimer’s disease (AD)-linked mutations in
the PSEN-1 gene lead to the early onset and increase the production of the aggregation-prone peptide
Aβ42. However, the PSEN-1 E318G variant has an unclear pathogenic role and is recently reported as a
genetic risk factor for AD. In particular, E318G variant presence correlated with increased cerebrospinal
fluid (CSF) levels of Total Tau (t-tau) and Phosphorylated Tau (p-tau).
Objective: We describe a large Italian family, which we followed from January 2003 to January 2018,
with the late-onset AD and the E318G variant, with the aim of assessing E318G-associated CSF or
plasma biochemical changes in biomarkers of dementia.
Method: CSF Aβ42, t-tau and p-tau, plasma Aβ42 and Aβ40 were assessed by ELISA tests, while CSF
amyloid peptides profile was investigated by mass spectrometry.
Results: We did not find any changes in CSF biochemical markers (Aβ42, t-tau, p-tau and amyloid peptides)
of asymptomatic E318G carriers in 2010 and 2012, but plasma Aβ40 was increased at the same
times. From 2003 to 2018, no asymptomatic E318G carrier developed AD.
Conclusion: Our follow-up of this family may help elucidate E318G’s role in AD and globally points to
a null effect of this variant.