Abeta43 is more frequent than Abeta40 in amyloid plaque cores from Alzheimer disease brains.
One hallmark of Alzheimer disease (AD) is the extracellular deposition of the amyloid beta-peptide (Abeta) in senile plaques. Two major forms of Abeta are produced, 40 (Abeta40) and 42 (Abeta42) residues long. The most abundant form of Abeta is Abeta40, while Abeta42 is more hydrophobic and more prone to form toxic oligomers and the species of particular importance in early plaque formation. Thus, the length of the hydrophobic C-terminal seems to be very important for the oligomerization and neurotoxicity of the Abeta peptide. Here we investigated which Abeta species are deposited in AD brain. We analyzed plaque cores, prepared from occipital and frontal cortex, from sporadic and familial AD cases and performed a quantitative study using Abeta standard peptides. Cyanogen bromide was used to generate C-terminal Abeta fragments, which were analyzed by HPLC coupled to an electrospray ionisation ion trap mass spectrometer. We found a longer peptide, Abeta43, to be more frequent than Abeta40. No variants longer than Abeta43 could be observed in any of the brains. Immunohistochemistry was performed and was found to be in line with our findings. Abeta1-43 polymerizes rapidly and we suggest that this variant may be of importance for AD.
Welander
Hedvig
H
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Dainippon Sumitomo Pharma Alzheimer Center, Novum, Huddinge, Sweden. hedvig.welander@ki.se
Frånberg
Jenny
J
Graff
Caroline
C
Sundström
Erik
E
Winblad
Bengt
B
Tjernberg
Lars O
LO
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001923:Brain Chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C098994:amyloid beta-protein (1-43)