Increased neuronal beta-amyloid precursor protein expression in human temporal lobe epilepsy: association with interleukin-1 alpha immunoreactivity.
Levels of immunoreactive beta-amyloid precursor protein and interleukin-1 alpha were found to be elevated in surgically resected human temporal lobe tissue from patients with intractable epilepsy compared with postmortem tissue from neurologically unaffected patients (controls). In tissue from epileptics, the levels of the 135-kDa beta-amyloid precursor protein isoform were elevated to fourfold (p < 0.05) those of controls and those of the 130-kDa isoform to threefold (p < 0.05), whereas those of the 120-kDa isoform (p > 0.05) were not different from control values. beta-Amyloid precursor protein-immunoreactive neurons were 16 times more numerous, and their cytoplasm and proximal processes were more intensely immunoreactive in tissue sections from epileptics than controls (133 +/- 12 vs. 8 +/- 3/mm2; p < 0.001). However, neither beta-amyloid precursor protein-immunoreactive dystrophic neurites nor beta-amyloid deposits were found in this tissue. Interleukin-1 alpha-immunoreactive cells (microglia) were three times more numerous in epileptics than in controls (80 +/- 8 vs. 25 +/- 5/mm2; p < 0.001), and these cells were often found adjacent to beta-amyloid precursor protein-immunoreactive neuronal cell bodies. Our findings, together with functions established in vitro for interleukin-1, suggest that increased expression of this protein contributes to the increased levels of beta-amyloid precursor protein in epileptics, thus indicating a potential role for both of these proteins in the neuronal dysfunctions, e.g., hyperexcitability, characteristic of epilepsy.
Sheng
J G
JG
Arkansas Children's Hospital Research Center, Department of Pediatrics, Little Rock.
Boop
F A
FA
Mrak
R E
RE
Griffin
W S
WS
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000032:analysis* / Q000378:metabolism; D015153:Blotting, Western; D002648:Child; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000032:analysis* / Q000276:immunology; D007536:Isomerism; D008297:Male; D017628:Microglia / Q000737:chemistry / Q000378:metabolism; D008875:Middle Aged; D009474:Neurons / Q000737:chemistry* / Q000378:metabolism; D013702:Temporal Lobe / Q000737:chemistry / Q000378:metabolism / Q000473:pathology
D016564:Amyloid beta-Protein Precursor; D007375:Interleukin-1