Secretory cleavage of beta-amyloid precursor protein in the cerebral white matter produces amyloidogenic carboxyl-terminal fragments.
To elucidate the metabolic process generating amyloid-beta protein (A beta) from beta-amyloid precursor protein (APP) in human brain, we partially purified secretory forms and carboxyl-terminal fragments (CTFs) of APP from the white matter of a Down's syndrome brain. We obtained secretory forms of APP which lack the entire A beta sequence and CTFs which contain the full-length A beta from the cerebral white matter. Some A beta-lacking secretory APP isoforms in the white matter were derived from APP695. These results suggest that amyloidogenic CTFs can be produced by secretory cleavage of APP which is anterogradely transported through the axon in human brain.
Tokuda
T
T
Department of Molecular Biology, Tokyo Institute of Psychiatry, Japan.
Tanaka
K
K
Kametani
F
F
Ikeda
S
S
Yanagisawa
N
N
D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D001370:Axonal Transport / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism*; D004314:Down Syndrome / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007536:Isomerism; D008875:Middle Aged; D010443:Peptide Chain Termination, Translational / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments