title: Formation of phospho-SAPK/JNK granules in the hippocampus is an early event in Alzheimer disease.
abstract: The mitogen-activated protein (MAP) kinase SAPK/JNK phosphorylates tau protein at many of its proline-directed serine/threonine residues in vitro and is a likely candidate kinase to phosphorylate the pathologically relevant S422 site on tau. Since phosphorylation of tau, particularly at S422, is a relatively early marker of AD and seems to precede tangle formation, it appears likely that an early form of activated SAPK/JNK might be detected by immunohistochemical means around the time that tau begins to aggregate into tangles. We report here that an antibody to phospho-SAPK/JNK (p-SAPK/JNK) reacts with several types of lesions including granular bodies in limbic areas; NFTs in limbic cortex and temporal neocortex; occasional neuritic plaques in temporal neocortex; and select axons in the hippocampus, entorhinal cortex, and inferior temporal cortex. In order to characterize the appearance of granular p-SAPK/JNK and determine if it appears early in disease, we employed an immunohistochemical study of postmortem limbic tissue from 20 cases ranging from Braak stages I-VI. By co-staining with anti-tau antibodies specific to different molecular events that occur during tangle evolution, we were able to identify the appearance of p-SAPK/JNK in early Braak stages with an increased elevation during the limbic stages of AD and during the early stages of the formation of individual hippocampal tangles.
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. s-lagalwar@northwestern.edu
authors.forename: Sarita
authors.initials: S
authors.lastname: Lagalwar
authors.forename: Angela L
authors.initials: AL
authors.lastname: Guillozet-Bongaarts
authors.forename: Robert W
authors.initials: RW
authors.lastname: Berry
authors.forename: Lester I
authors.initials: LI
authors.lastname: Binder
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000704:Analysis of Variance; D017209:Apoptosis / Q000502:physiology; D002452:Cell Count / Q000379:methods; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D008875:Middle Aged; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation
chemical_list: D009419:Nerve Tissue Proteins; D048055:Mitogen-Activated Protein Kinase 8