Differential expression of TGF-beta 1, 2 and 3 isotypes in Alzheimer's disease: a comparative immunohistochemical study with cerebral infarction, aged human and mouse control brains.
Based upon the hypothesis that growth regulatory and inflammatory mechanisms participate in the pathogenesis of Alzheimer's disease, we studied cases of Alzheimer's disease for immunoreactivity to each of the three mammalian transforming growth factor beta (TGF-beta) isotypes: TGF-beta 1, TGF-beta 2, TGF-beta 3. Results were compared with those seen in control brains and in a destructive pathological process, subacute infarction. In the cases of Alzheimer's disease, TGF-beta 1 immunoreactivity was limited to neuritic profiles within senile plaques. Neuronal neurofibrillary tangles, plaque neurites, microglia, astrocytes and macrophages expressed TGF-beta 2 immunoreactivity. TGF-beta 3 produced strikingly selective staining of Hirano bodies. In contrast, in cases with infarction, reactive astrocytes and macrophages were positive with all three antibodies. Ramified microglia labeled selectively, as in the Alzheimer brains, with the TGF-beta 2 antibody. Subtle generalized astrocyte and microglial immunoreactivity for TGF-beta 2 was seen in pathological and control brains. The localization of TGF-beta isotypes to the lesions of Alzheimer's disease supports the hypothesis that these cytokines may influence lesion expression. Their presence in reactive cells associated with cerebral infarction suggest that they may play a broader role in the pathogenesis of CNS disease.
Peress
N S
NS
Pathology Services, Department of Veterans Affairs Medical Center, Northport, New York, USA.
Perillo
E
E
D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002544:Cerebral Infarction / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008815:Mice, Inbred Strains; D017628:Microglia / Q000648:ultrastructure; D016212:Transforming Growth Factor beta / Q000145:classification* / Q000235:genetics*
D016212:Transforming Growth Factor beta