PSEN1 mutation carriers present lower cerebrospinal fluid amyoid-β42 levels than sporadic early-onset Alzheimer's disease patients but no differences in neuronal injury biomarkers.

Most cases of early-onset Alzheimer's disease (EOAD) are sporadic. A minority of EOAD are caused by spe- cific genetic defects in PSEN1, PSEN2, or APP genes. Magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarker comparisons between sporadic and monogenic EOAD are practically inexistent. CSF and MRI data from 14 amnestic- onset sporadic EOAD (sEOAD) subjects were compared with data from 8 symptomatic PSEN1 mutation carriers (PSEN1) and 14 age-matched cognitively-preserved controls. CSF concentrations of amyloid- (A)42, total tau (t-tau), and phos- phorylated tau (p-tau) were determined. Cortical thickness (CTh) and grey matter loss were compared between groups and correlated with CSF biomarkers. PSEN1 had significantly lower CSF A42 levels compared to sEOAD (mean 244.8 pg/ml versus 381.4 pg/ml; p = 0.006), but no differences in t-tau or p-tau. Both sEOAD and PSEN1 showed widespread CTh loss in AD target areas when compared with controls. No differences were found in the direct comparison between sEOAD and PSEN1 CTh after adjusting for age and Mini-Mental Status Examination scores. Neither was a correlation found between A42 levels and CTh. CTh in the left superior parietal and caudal middle frontal areas was negatively correlated with t-tau values. In conclusion, PSEN1 had lower A42 CSF levels compared with sEOAD, suggesting a greater cerebral deposition of A42.