| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel; and
Department of Medicine, Rabin Medical Center, Petach-Tiqva, affiliated with the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Alzheimer’s disease (AD) is the most common human neurodegenerative disease, leading to progressive cognitive decline and eventually death. The prevailing paradigm on the pathogenesis of AD is that abnormally folded proteins accumulate in specific brain areas and lead to neuronal loss via apoptosis. In recent years it has become evident that an inflammatory and possibly autoimmune component exists in AD. Moreover, recent data demonstrate that immunization with amyloid-
peptide is therapeutically effective in AD. The nature of CNS Ags that are the target of immune attack in AD is unknown. To identify potential autoantigens in AD, we tested sera IgG Abs of AD patients in immunoblots against brain and other tissue lysates. We identified a 42-kDa band in brain lysates that was detected with >50% of 45 AD sera. The band was identified by mass spectrometry to be aldolase A. Western blotting with aldolase using patient sera demonstrated a band of identical size. The Ab reactivity was verified with ELISAs using aldolase. One of 25 elderly control patients and 3 of 30 multiple sclerosis patients showed similar reactivity (p < 0.002). In enzymatic assays, anti-aldolase positive sera were found to inhibit the enzyme’s activity, and the presence of the substrate (fructose 1,6-diphosphate) enhanced Ab binding. Immunization of rats and mice with aldolase in complete Freund’s adjuvant was not pathogenic. These findings reveal an autoimmune component in AD, point at aldolase as a common autoantigen in this disease, and suggest a new target for potential immune modulation.
This article has been cited by other articles:
|
|
 |
|
  B. Jang, E. Kim, J.-K. Choi, J.-K. Jin, J.-I. Kim, A. Ishigami, N. Maruyama, R. I. Carp, Y.-S. Kim, and E.-K. Choi Accumulation of Citrullinated Proteins by Up-Regulated Peptidylarginine Deiminase 2 in Brains of Scrapie-Infected Mice: A Possible Role in Pathogenesis Am. J. Pathol., October 1, 2008; 173(4): 1129 - 1142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. X. Zhu, H. A. Doyle, M. J. Mamula, and D. W. Aswad Protein Repair in the Brain, Proteomic Analysis of Endogenous Substrates for Protein L-Isoaspartyl Methyltransferase in Mouse Brain J. Biol. Chem., November 3, 2006; 281(44): 33802 - 33813. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
