Expression of the protooncogene bcl-2 in Alzheimerʹs disease brain

To investigate the role of the apopotosis-related protooncogene bcl-2 in Alzheimerʹs disease (AD), we compared levels of its protein product, designated Bcl-2, in AD and nondemented (ND) age-matched control neocortical samples. The 26 kD Bcl-2 protein is increased in expression by more than three-fold in AD compared to ND samples as detected by immunoblots. Immunohistochemical analyses give similar results. In AD patients Bcl-2 immunoreactivity is dense and profuse and appears to occur on reactive astrocytes, whereas Bcl-2 immunoreactivity of astrocytes in ND patients is light and sparse. Staining of both gray and white matter is observed but is most prominent in the latter. Increased expression of Bcl-2 by astrocytes may partially underlie their resistance to loss in AD. By contrast, neuronal Bcl-2 immunoreactivity is more sparse and equivocal, perhaps reflecting the vulnerability of this cell type to apoptotic mechanisms in AD. High levels of Bcl-2 in glial cells may aid in cell survival of reactive astrocytes resulting in either beneficial or deleterious effects on neuronal viability.