The temporal localization of frame-shift ubiquitin-B and amyloid precursor protein, and complement proteins in the brain of non-demented control patients with increasing Alzheimer's disease pathology.
Transcriptional misreading of dinucleotide repeats that generates deletions in RNA and produces frame-shift proteins with loss of function has been reported in Alzheimer's disease (AD). Here frame-shift ubiquitin-B and amyloid precursor protein were immunochemically shown to exist in the brain of high pathology control (HPC) patients with AD pathology but without prior dementia. These proteins were absent in low pathology control patients with limited AD pathology and no dementia. Since the HPC patients can be regarded as preclinical AD patients, our results suggest the accumulation of these proteins involved in the initial steps of AD pathogenesis. By contrast, complement proteins were detected in the AD patients, whereas only trace amounts were found in the HPC patients, indicating the involvement of complement proteins in the later stage of AD dementia.
Konishi
Yoshihiro
Y
Haldeman Laboratory of Molecular and Cellular Neurobiology, Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ 85351, USA.
Beach
Thomas
T
Sue
Lucia I
LI
Hampel
Harald
H
Lindholm
Kristina
K
Shen
Yong
Y
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000906:Antibodies; D015153:Blotting, Western; D001921:Brain / Q000033:anatomy & histology / Q000473:pathology; D003165:Complement System Proteins / Q000378:metabolism*; D003704:Dementia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D025801:Ubiquitin; D003165:Complement System Proteins