Co-localization and distribution of cerebral APP and SP1 and its relationship to amyloidogenesis

Alzheimer's disease is characterized by amyloid-β peptide (Aβ)-loaded plaques in the brain. Aβ is a cleavage fragment of amyloid-β protein precursor (APP) and over production of APP may lead to amyloidogenesis. The regulatory region of the APP gene contains consensus sites recognized by the transcription factor, specificity protein 1 (SP1), which has been shown to be required for the regulation of APP and Aβ. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and localization of SP1, APP, and Aβ in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and Aβ are similar and neuronal in origin. Their distribution is abundant in various layers of neocortex, but restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell layer of hippocampus. These findings suggest that overproduction of Aβ in vivo may be associated with transcriptional pathways involving SP1 and the APP gene.