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

The pattern of deposition of amyloid beta protein (Abeta) was investigated, using the monoclonal antibodies BA27 and BC05 detecting the C-terminal species Abeta40 and Abeta42(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 Abeta40 and Abeta42(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 Abeta40 and Abeta42(43), with only few diffuse Abeta42(43) containing plaques. The area fraction of Abeta40, and the ratio between Abeta40 and Abeta42(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 Abeta42(43), however, did not significantly differ between these three groups. The unusual nature of the Abeta 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.