Amyloid precursor protein in peripheral mononuclear cells is up-regulated with cell activation.
The deposition of beta/A4 protein in extraneural organs of patients with Alzheimer disease suggests that this peptide may in part be derived from a peripheral precursor. We studied expression of amyloid precursor protein (APP) in PBMC. APP expression was detectable in resting PBMC by northern blot analysis, immunoblotting studies, and immunohistochemistry. By reverse transcription-polymerase chain reaction, the 751 and 770 APP transcripts containing the Kunitz protease inhibitor (KPI) domain were approximately 10-fold more abundant than the 695 transcript lacking the KPI domain. Activation of PBMC with the lectin PHA-P was associated with an increase in apparent intracellular APP content by cytofluorometry, and an increase in the proportion of the 695 APP transcript lacking the KPI domain. We conclude that resting and activated PBMC express APP and could contribute to a circulating pool of this protein. In addition, PBMC APP is up-regulated with mitogenic stimulation and may participate in the regulation of activation of these cells.
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Quebec, Canada.
S
S
Ledoux
N
N
Rebai
A
A
Dagenais
I T
IT
Shaw
J
J
Nalbantoglu
R P
RP
Sekaly
N R
NR
Cashman
D017398:Alternative Splicing; D000682:Amyloid / Q000096:biosynthesis; D016564:Amyloid beta-Protein Precursor / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002455:Cell Division; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry* / Q000276:immunology; D008214:Lymphocytes / Q000737:chemistry; D008969:Molecular Sequence Data; D009474:Neurons / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger