Cerebrospinal fluid of Alzheimer patients promotes β-amyloid fibril formation in vitro

Cerebral deposition of amyloid β-peptide (Aβ) is an invariant feature of Alzheimer's disease (AD). To answer why soluble Aβ does not aggregate to β-amyloid fibrils (fAβ) in the brain of normal humans, we examined the influence of cerebrospinal fluid (CSF) obtained from AD and non-AD patients on the formation of fAβ(1-40) and fAβ(1-42) in vitro, by using fluorescence spectroscopy with thioflavin T and electron microscopy. Although the CSF obtained from both groups inhibited the formation of both fAβ(1-40) and fAβ(1-42), the CSF from non-AD patients inhibited the formation of fAβs more strongly than that from AD patients. In AD patients, the final levels of fAβs formation showed a significant negative correlation with the Aβ(1-42) level in CSF. These results indicate that fAβ deposition in the brain of AD may be enhanced by the decrease of specific inhibitory factors and/or by the increase of specific accelerating factors in CSF.