Amyloid precursor protein and ubiquitin immunoreactivity in dystrophic axons is not unique to Alzheimer's disease.
A distinctive feature of Alzheimer's disease (AD) is the presence of dystrophic neurites that immunoreact with antibodies to amyloid precursor protein (APP) and ubiquitin (Ub). The authors examined dystrophic axons (DA) present in other chronic conditions such as familial infantile neuroaxonal dystrophy (INAD), aging, cystic fibrosis, and biliary obstruction as well as in conditions of shorter duration such as human immunodeficiency virus (HIV) leucoencephalopathy, infarction and radiation therapy to determine whether APP and Ub immunoreactivity was unique to the DA of AD. A large number of DA immunoreacted with antibodies to the A4, C- and N-terminal regions of APP as well as to Ub. Ub and APP immunoreactivities often, but not always, colocalized. "Acute" DA generally reacted more intensely and in larger number with antibodies to APP than to Ub, whereas the reverse was true for "chronic" DA. Structureless DA immunostained diffusely. In DA with cores or granules, the Ub immunoreaction was occasionally limited to these structures, whereas reaction with antibodies to APP was more diffuse. In view of the contention that impairment of proteolysis is the common pathogenetic step in the formation of DA, Ub immunoreactivity in all DA may indicate a vicarious attempt to degrade accumulated components through an activation of the Ub system. The role of APP in the formation of DA remains to be determined.
Cochran
E
E
Division of Neuropathology, Case Western Reserve University, Cleveland, Ohio 44106.
Bacci
B
B
Chen
Y
Y
Patton
A
A
Gambetti
P
P
Autilio-Gambetti
L
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D001369:Axons / Q000378:metabolism*; D002648:Child; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D011498:Protein Precursors / Q000378:metabolism*; D013194:Staining and Labeling; D014452:Ubiquitins / Q000378:metabolism*
D000682:Amyloid; D011498:Protein Precursors; D014452:Ubiquitins