PMID- 9278049
OWN - NLM
STAT- MEDLINE
DCOM- 19970912
LR  - 20210402
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 388
IP  - 6645
DP  - 1997 Aug 28
TI  - Microglial activation by Alzheimer amyloid precursor protein and modulation by 
      apolipoprotein E.
PG  - 878-81
AB  - A role for beta-amyloid precursor protein (beta-APP) in the development of 
      Alzheimer's disease has been indicated by genetics, and many conditions in which 
      beta-APP is raised have been associated with an increased risk of Alzheimer's 
      disease or an Alzheimer's-like pathology. Inflammatory events may also contribute 
      to Alzheimer's disease. Here we investigate whether a secreted derivative of 
      beta-APP (sAPP-alpha) can induce inflammatory reactions in microglia, which are 
      brain cells of monocytic lineage. We found that treatment with sAPP-alpha 
      increased markers of activation in microglia and enhanced their production of 
      neurotoxins. The ability of sAPP-alpha to activate microglia was blocked by prior 
      incubation of the protein with apolipoprotein E3 but not apolipoprotein E4, a 
      variant associated with an increased risk for Alzheimer's. A product of 
      amyloidogenic beta-APP processing (sAPP-beta) also activated microglia. Because 
      sAPP-beta is deficient in the neuroprotective activity shown by sAPP-alpha, our 
      results indicate that increased amyloidogenic processing could adversely affect 
      the balance of sAPP activities that determine neuronal viability.
FAU - Barger, S W
AU  - Barger SW
AD  - Donald W. Reynolds Department of Geriatrics, University of Arkansas for Medical 
      Sciences, Little Rock 72205, USA. swbarger@life.uams.edu
FAU - Harmon, A D
AU  - Harmon AD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (APP protein, human)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Interleukin-1)
RN  - 0 (NF-kappa B)
RN  - 0 (Peptide Fragments)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
SB  - IM
MH  - Alzheimer Disease/*metabolism
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - Apolipoproteins E/*metabolism
MH  - Cell Death
MH  - Cell Line
MH  - Gene Expression Regulation
MH  - Humans
MH  - Inflammation/metabolism
MH  - Interleukin-1/biosynthesis/genetics
MH  - Microglia/cytology/*metabolism
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide Synthase/biosynthesis/genetics
MH  - Peptide Fragments/*metabolism
MH  - Rats
EDAT- 1997/08/28 00:00
MHDA- 2001/03/23 10:01
CRDT- 1997/08/28 00:00
PHST- 1997/08/28 00:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1997/08/28 00:00 [entrez]
AID - 10.1038/42257 [doi]
PST - ppublish
SO  - Nature. 1997 Aug 28;388(6645):878-81. doi: 10.1038/42257.