Amyloid β protein (Aβ) deposition in chromosome 14–linked Alzheimer's disease: Predominance of Aβ42(43)

Amyloid β protein (Aβ) deposition was investigated in the frontal cortex of 8 cases of (genetically confirmed) chromosome 14-linked Alzheimer's disease (AD) using the end-specific monoclonal antibodies BA27 and BC05 to detect the presence of Aβ 40 and Aβ 42(43) , respectively. In all patients, Aβ 42(43) was the predominant peptide species present. The total amount of Aβ 40 and Aβ 42(43) deposited was more than twice the amount deposited in cases of sporadic AD of similar disease duration, although the ratio between the extent of Aβ 40 and Aβ 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 Aβ 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).