Neuronal localization of the TNF alpha converting enzyme (TACE) in brain tissue and its correlation to amyloid plaques

The tumor necrosis factor (TNF)-alpha converting enzyme (TACE) can cleave t he cell-surface ectodomain of the amyloid-beta precursor protein (APP), thu s decreasing the generation of amyloid-beta (A beta) by cultured non-neuron al cells. While the amyloidogenic processing of APP in neurons is linked to the pathogenesis of Alzheimer's disease (AD), the expression of TACE in ne urons has not yet been examined. Thus, we assessed TACE expression in a ser ies of neuronal and non-neuronal cell types by Western blots. We found that TACE was present in neurons and was only faintly detectable in lysates of astrocytes, oligodendrocytes, and microglial cells. Immunohistochemical ana lysis was used to determine the cellular localization of TACE in the human brain, and its expression was detected in distinct neuronal populations, in cluding pyramidal neurons of the cerebral cortex and granular cell layer ne urons in the hippocampus. Very low levels of TACE were seen in the cerebell um, with Purkinje cells at the granular-molecular boundary staining faintly . Because TACE was localized predominantly in areas of the brain that are a ffected by amyloid plaques in AD, we examined its expression in a series of AD brains. We found that AD and control brains showed similar levels of TA CE staining, as well as similar patterns of TACE expression. By double labe ling for A beta plaques and TACE, we found that TACE-positive neurons often colocalized with amyloid plaques In AD brains. These observations support a neuronal role for TACE and suggest a mechanism for its involvement in AD pathogenesis as an antagonist of A beta formation. (C) 2001 John Wiley & So ns, Inc.