Abstract:
:Alzheimer beta/A4 amyloid precursor protein (APP) has been suggested to play a central role in the pathogenesis of Alzheimer disease. We have measured the content of different species of APP holoprotein and carboxyl-terminal fragments in human brains from young individuals, nondemented aged individuals, and aged individuals with Alzheimer disease. By using an antibody directed against the cytoplasmic domain of APP, five species were resolved. Three of these, of molecular masses 106, 113, and 133 kDa, represent presumptive immature and mature isoforms of APP holoprotein. Two smaller proteins, of molecular masses 15 and 19 kDa, represent presumptive proteolytic carboxyl-terminal fragments of APP. The 133-, 113-, 106-, and 15-kDa species were found in both grey and white matter, whereas the 19-kDa species was found only in grey matter. Total APP immunoreactivity (sum of all five species) and the levels of the 113-, 106-, and 15-kDa species were not significantly different in brain samples from young individuals, nondemented aged individuals, and aged individuals with Alzheimer disease. In contrast, the levels of the 133- and 19-kDa species increased 2- to 3-fold with age. A correlation was observed between the levels of the 133- and 19-kDa species, suggesting a possible precursor-product relationship. The size of the 19-kDa fragment indicated that it might have an intact beta/A4 domain and therefore be amyloidogenic. The age-dependent increase either in a mature APP isoform and/or in a putative amyloidogenic fragment could explain why Alzheimer disease is associated with advanced age.
journal_name
Proc Natl Acad Sci U S Aauthors
Nordstedt C,Gandy SE,Alafuzoff I,Caporaso GL,Iverfeldt K,Grebb JA,Winblad B,Greengard Pdoi
10.1073/pnas.88.20.8910subject
Has Abstractpub_date
1991-10-15 00:00:00pages
8910-4issue
20eissn
0027-8424issn
1091-6490journal_volume
88pub_type
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