Expression and distribution of amyloid precursor protein-like protein-2 in Alzheimer's disease and in normal brain.
Amyloid precursor-like protein-2 (APLP-2) belongs to a family of homologous amyloid precursor-like proteins. In the present study we report on the expression and distribution of APLP-2 in fetal and adult human brain and in brains of patients with Alzheimer's disease. We demonstrate that APLP-2 mRNAs encoding isoforms predicted to undergo post-translational modification by chondroitin sulfate glycosaminoglycans are elevated in fetal and aging brains relative to the brains of young adults. Immunocytochemical labeling with APLP-2-specific antibodies demonstrates APLP-2 immunoreactivity in cytoplasmic compartments in neurons and astrocytes, in large part overlapping the distribution of the amyloid precursor protein. In Alzheimer's disease brain, APLP-2 antibodies also label a subset of neuritic plaques. APLP-2 immunoreactivity is particularly conspicuous in large dystrophic neurites that also label with antibodies specific for APP and chromogranin A. In view of the age-dependent increase in levels of chondroitin sulfate glycosaminoglycan-modified forms of APLP-2 in aging brain and the accumulation of APLP-2 in dystrophic presynaptic elements, we suggest that APLP-2 may play roles in neuronal sprouting or in the aggregation, deposition, and/or persistence of beta-amyloid deposits.
Crain
B J
BJ
Department of Pathology (Neuropathology Laboratory), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Hu
W
W
Sze
C I
CI
Slunt
H H
HH
Koo
E H
EH
Price
D L
DL
Thinakaran
G
G
Sisodia
S S
SS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D001923:Brain Chemistry; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger