Cerebrospinal fluid levels of phosphorylated tau and Aβ1-38/Aβ1-40/Aβ1-42 in Alzheimer's disease with PS1 mutations

We studied seven cases of Alzheimer's disease (AD). Six of the patients had presenilin 1 (PS1) mutations (PS1AD). Three novel PS1 mutations (T99A, H131R and L219R) and three other missense mutations (M233L, H163R and V272A) were found in the PS1AD group. We measured the levels of phosphorylated tau (ptau-181, ptau-199) and A beta (A beta 1-42, A beta 1-40 and A beta 1-38) in the cerebrospinal fluid (CSF) of PS1AD patients, early-onset sporadic AD (EOSAD), late-onset sporadic AD (LOSAD) and non-demented subjects (ND). The CSF levels of A beta 1-42 in the three AD groups were significantly lower than those of the ND group (p < 0.0001). CSF levels of A beta 1-42 in the PS1AD group were significantly lower than those in the two sporadic AD groups. The A beta 1-40 and A beta 1-38 levels in the CSF of the PS1AD group were significantly lower than those of the three other groups (p < 0.0001, respectively). The levels of A beta 1-40, A beta 1-38 and A beta 1-42 in the CSF of the PS1AD group remained lower than those of the ND group for 4 years. Not only CSF A beta 1-42, but also A beta 1-40 and A beta 1-38 decreased in the advanced stages of PS1AD.