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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
Author(s) -
Mann D. M. A.,
Takeuchi A.,
Sato S.,
Cairns N. J.,
Lantos P. L.,
Rossor M. N.,
Haltia M.,
Kalimo H.,
Iwatsubo T.
Publication year - 2001
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1046/j.1365-2990.2001.00316.x
Subject(s) - senile plaques , presenilin , pathology , exon , biology , alzheimer's disease , microbiology and biotechnology , mutation , chemistry , gene , genetics , medicine , disease
The pattern of deposition of amyloid β protein (Aβ) was investigated, using the monoclonal antibodies BA27 and BC05 detecting the C‐terminal species Aβ 40 and Aβ 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 Aβ 40 and Aβ 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 Aβ 40 and Aβ 42(43) , with only few diffuse Aβ 42(43) containing plaques. The area fraction of Aβ 40 , and the ratio between Aβ 40 and Aβ 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 Aβ 42(43) , however, did not significantly differ between these three groups. The unusual nature of the Aβ 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.