PMID- 1690426
OWN - NLM
STAT- MEDLINE
DCOM- 19900425
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 87
IP  - 6
DP  - 1990 Mar
TI  - Defined neurofilament, tau, and beta-amyloid precursor protein epitopes 
      distinguish Alzheimer from non-Alzheimer senile plaques.
PG  - 2249-53
AB  - Eight antisera and one monoclonal antibody to synthetic peptides that 
      corresponded to domains extending over the entire length of the beta-amyloid 
      precursor protein (beta-APP), and an antiserum to the full-length 695-amino acid 
      form of the beta-APP, were raised to probe the composition of the core and corona 
      of senile plaques (SPs). We localized distinct beta-APP domains, including the 
      beta-amyloid protein or A4 region, within the SPs of 13 end-stage Alzheimer 
      disease (AD) and 13 age-matched control samples of hippocampus and entorhinal 
      cortex. The composition of SPs also was probed with antibodies to defined 
      epitopes in tau (tau) as well as the large and mid-size neurofilament (NF) 
      proteins. The most important observations were that beta-APP domains outside the 
      A4 region were largely restricted to SP coronas in the AD samples, together with 
      tau and NF determinants, whereas the same epitopes were absent from A4-positive 
      blood vessels and exceptionally rare in non-AD SPs. Indeed, samples from a subset 
      of the non-AD cases contained a considerable number of A4-positive SPs totally 
      devoid of any of the other beta-APP, tau, and NF epitopes. These observations 
      suggest that the deposition of the A4 protein in AD SPs results from the local 
      processing of beta-APPs in association with tau and NF protein fragments. It is 
      unclear whether this association is fortuitous or linked by common mechanisms. 
      However, differences between the complement of beta-APP, tau, and NF protein 
      epitopes in AD versus non-AD brains implicate a defect involving one or more 
      steps in the posttranslational modification, degradation, or elimination of these 
      proteins in AD brains, and this may account for the massive numbers of SPs that 
      characterize AD.
FAU - Arai, H
AU  - Arai H
AD  - Department of Pathology, University of Pennsylvania School of Medicine, 
      Philadelphia 19104.
FAU - Lee, V M
AU  - Lee VM
FAU - Otvos, L Jr
AU  - Otvos L Jr
FAU - Greenberg, B D
AU  - Greenberg BD
FAU - Lowery, D E
AU  - Lowery DE
FAU - Sharma, S K
AU  - Sharma SK
FAU - Schmidt, M L
AU  - Schmidt ML
FAU - Trojanowski, J Q
AU  - Trojanowski JQ
LA  - eng
GR  - AG06107/AG/NIA NIH HHS/United States
GR  - AG06901/AG/NIA NIH HHS/United States
GR  - MH43880/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Amyloid)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Epitopes)
RN  - 0 (Immune Sera)
RN  - 0 (Intermediate Filament Proteins)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neurofilament Proteins)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Protein Precursors)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Alzheimer Disease/*pathology
MH  - Amyloid/*analysis/immunology
MH  - Amyloid beta-Protein Precursor
MH  - Antibodies, Monoclonal
MH  - Epitopes/*analysis
MH  - Hippocampus/*pathology
MH  - Humans
MH  - Immune Sera
MH  - Immunoblotting
MH  - Intermediate Filament Proteins/*analysis/immunology
MH  - Microtubule-Associated Proteins/*analysis/immunology
MH  - Nerve Tissue Proteins/*analysis
MH  - Neurofilament Proteins
MH  - Protease Inhibitors/*analysis
MH  - Protein Precursors/*analysis/immunology
MH  - tau Proteins
PMC - PMC53664
EDAT- 1990/03/11 19:15
MHDA- 2001/03/28 10:01
PMCR- 1990/09/01
CRDT- 1990/03/11 19:15
PHST- 1990/03/11 19:15 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1990/03/11 19:15 [entrez]
PHST- 1990/09/01 00:00 [pmc-release]
AID - 10.1073/pnas.87.6.2249 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1990 Mar;87(6):2249-53. doi: 10.1073/pnas.87.6.2249.