Presenilin-1 exists in the axoplasm fraction in the brains of aged Down's syndrome subjects and non-demented individuals.
Missense mutations in the presenilin-1 (PS-1) gene are known to be responsible for early-onset familial Alzheimer's disease (AD). The normal physiological functions of PS-1 are still incompletely understood, although data on the intracellular localization of PS-1 are accumulating, indicating that it exists mainly in endoplasmic reticulum and Golgi compartments. To investigate the localization and functions of PS-1 in the human brain, we separated axoplasm fractions from the cerebral white matter of Down's syndrome (DS) subjects with AD pathology and non-demented individuals using the axonal flotation method, and analyzed them immunocytochemically. All axoplasm fractions contained the 28-34 kDa amino-terminal fragment and the 18 kDa carboxy-terminal fragment of PS-1, although there was no specific abnormality of this protein in the DS brains with AD pathology. This finding indicates that there is intracellular trafficking of PS-1 through the axons in the human brain, and thus provides new information about the physiology of PS-1.
Sekijima
Y
Y
Department of Medicine (Neurology), Shinshu University School of Medicine, Matsumoto, Japan.
Kametani
F
F
Tanaka
K
K
Okochi
M
M
Usami
M
M
Mori
H
H
Tokuda
T
T
Ikeda
S
S
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002458:Cell Fractionation; D003593:Cytoplasm / Q000378:metabolism*; D004314:Down Syndrome / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D053764:Presenilin-1
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1