Cases of Alzheimer's disease due to deletion of exon 9 of the presenilin-1 gene show an unusual but characteristic β-amyloid pathology known as 'cotton wool' plaques

The pattern of deposition of amyloid beta protein (A beta) was investigated, using the monoclonal antibodies BA27 and BC05 detecting the C-terminal species A beta (40) and A beta (42(43)), in six cases of Alzheimer's disease (AD) due to deletions in exon 9 of PS-1 gene. These cases are characterized histologically by the presence of very large rounded plaques within the frontal cortex, known as 'cotton wool' plaques, composed of both A beta (40) and A beta (42(43)) that are relatively free from neuritic changes and glial cell components, and usually devoid of a compact amyloid core. In the cerebellum the plaques are almost entirely of a compact type, again composed of A beta (40) and A beta (42(43)), with only few diffuse A beta (42(43)) containing plaques. The area fraction of A beta (40), and the ratio between A beta (40) and A beta (42(43)), in frontal cortex was significantly higher than that seen in other cases of AD due to different PS-1 mutations, or in cases of sporadic AD, all of similar APO E genotype. The area fractions of A beta (42(43)), however, did not significantly differ between these three groups. The unusual nature of the A beta deposition in these cases may reflect the uniqueness of the mutation, which results in a failure to constitutively cleave the PS-1 holoprotein into its active form, and the effect this might have on APP trafficking and catabolism.