AMYLOID-BETA PROTEIN (A-BETA) DEPOSITION IN CHROMOSOME 14-LINKED ALZHEIMERS-DISEASE - PREDOMINANCE OF A-BETA(42(43))

Amyloid beta protein (A beta) deposition was investigated in the front al cortex of 8 cases of (genetically confirmed) chromosome 14-linked A lzheimer's disease (AD) using the end-specific monoclonal antibodies B A27 and BC05 to detect the presence of A beta(40) and A beta(42(43)), respectively. In all patients, A beta(42(43)) was the predominant pept ide species present. The total amount of A beta(40) and A beta(42(43)) deposited was more than twice the amount deposited in cases of sporad ic AD of similar disease duration, although the ratio between the exte nt of A beta(40) and A beta(42(43)) deposition was unaltered, compared with sporadic AD. Therefore, (one of) the effects of the mutations in the presenilin 1:PS-1 (S182) gene may be to cause or at least promote an early and excessive deposition of A beta(42(43)) within the brain, a property shared with other inherited forms of AD, such as those due to amyloid precursor protein mutations, and Down's syndrome (trisomy 21).