Altered ?-secretase activity in mild cognitive impairment and Alzheimer's disease.

ABSTRACT: We investigated why the cerebrospinal fluid (CSF) concentrations of A?42 are lower in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. Because A?38/42 and A?40/43 are distinct product/precursor pairs, these four species in the CSF together should faithfully reflect the status of brain ?-secretase activity, and were quantified by specific enzyme-linked immunosorbent assays in the CSF from controls and MCI/AD patients. Decreases in the levels of the precursors, A?42 and 43, in MCI/AD CSF tended to accompany increases in the levels of the products, A?38 and 40, respectively. The ratios A?40/43 versus A?38/42 in CSF (each representing cleavage efficiency of A?43 or A?42) were largely proportional to each other but generally higher in MCI/AD patients compared to control subjects. These data suggest that ?-secretase activity in MCI/AD patients is enhanced at the conversion of A?43 and 42 to A?40 and 38, respectively. Consequently, we measured the in vitro activity of raft-associated ?-secretase isolated from control as well as MCI/AD brains and found the same, significant alterations in the ?-secretase activity in MCI/AD brains.

SUBMITTER: Kakuda N 

PROVIDER: S-EPMC3376855 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature