Amyloid beta protein 42(43) in cerebrospinal fluid of patients with Alzheimer's disease

To investigate the pathomechanism of amyloid beta protein (A beta) deposition in brains with Alzheimer's disease (AD), cerebrospinal fluid (CSF) levels of A beta species (CSF-A beta) with different carboxy termini, i.e. A beta X-40 and A beta X-42(43) as well as A beta 1-40 and A beta 1-42(43), were measured in patients with AD and age-matched controls without dementia (CTR) using sandwich enzyme-linked immunosorbent assays (ELISAs). The present study revealed that both CSF-A beta X-42(43) and A beta 1-42(43) levels were significantly lower in the AD patients (P<0.005) than in the CTR group, whereas neither CSF-A beta X-40 nor CSF-A beta 1-40 levels showed any differences between the two groups. In addition, although there was no difference between the ratios of A beta X-40 to A beta 1-40 in the AD and CTR groups, the ratios of A beta X-42(43) to A beta 1-42(43) were increased in the AD group compared with those in the CTR group (P<0.05). Therefore, it can be assumed that the ratios of amino terminal truncations and/or modifications of CSF-A beta 42(43) with carboxy termini ending at residue 42(43) were more increased in the AD group than in the CTR group. Increased adsorption of A beta 42(43) to A beta deposition in AD brains, decreased secretion of A beta 42(43) to CSF and/or increased clearance of A beta 42(43) from CSF might explain the diminished levels of A beta 42(43) in the CSF of AD patients. In addition, CSF-A beta 42(43) could reflect increased amino terminal truncations and/or modifications of A beta 42(43) in AD brains. (C) 1997 Elsevier Science B.V.