Alzheimer's disease and control brain contain soluble derivatives of the amyloid protein precursor that end within the beta amyloid protein region.
The 39-43 amino acid beta amyloid protein (A beta) that deposits as amyloid in the brains of patients with Alzheimer's disease (AD) is encoded as an internal sequence within a larger membrane-associated protein known as the amyloid protein precursor (APP). In cultured cells, the APP is normally cleaved within the A beta to generate a large secreted derivative and a small membrane-associated fragment. Neither of these derivatives can produce amyloid because neither contains the entire A beta. Our study was designed to determine whether the soluble APP derivatives in human brain end within the A beta as described in cell culture or whether AD brain produces potentially amyloidogenic soluble derivatives that contain the entire A beta. We find that both AD and control brain contain nonamyloidogenic soluble derivatives that end at position 15 of the A beta. We have been unable to detect any soluble derivatives that contain the entire A beta in either the AD or control brain.
Pasternack
J M
JM
Division of Neuropathology, Case Western Reserve University, Cleveland, Ohio 44106.
Palmert
M R
MR
Usiak
M
M
Wang
R
R
Zurcher-Neely
H
H
Gonzalez-De Whitt
P A
PA
Fairbanks
M B
MB
Cheung
T
T
Blades
D
D
Heinrikson
R L
RL
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D001923:Brain Chemistry; D003488:Cyanogen Bromide; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry
D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D003488:Cyanogen Bromide