AMYLOID-BETA PROTEIN-42(43) IN CEREBROSPINAL-FLUID OF PATIENTS WITH ALZHEIMERS-DISEASE

To investigate the pathomechanism of amyloid beta protein (A beta) dep osition in brains with Alzheimer's disease (AD), cerebrospinal fluid ( CSF) levels of A beta species (CSF-A beta) with different carboxy term ini, 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 cont rols 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 pat ients (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 gro ups. 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 comp ared with those in the CTR group (P<0.05). Therefore, it can be assume d that the ratios of amino terminal truncations and/or modifications o f 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 adsor ption of A beta 42(43) to A beta deposition in AD brains, decreased se cretion of A beta 42(43) to CSF and/or increased clearance of A beta 4 2(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.