title: Co-localization and distribution of cerebral APP and SP1 and its relationship to amyloidogenesis.
abstract: Alzheimer's disease is characterized by amyloid-beta peptide (Abeta)-loaded plaques in the brain. Abeta is a cleavage fragment of amyloid-beta 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 Abeta. To understand the role of SP1 in APP biogenesis, herein we have characterized the relative distribution and localization of SP1, APP, and Abeta in various brain regions of rodent and primate models using immunohistochemistry. We observed that overall distribution and cellular localization of SP1, APP, and Abeta 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 Abeta in vivo may be associated with transcriptional pathways involving SP1 and the APP gene.
authors.affiliation: Neurotoxicology and Epigenomics Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Brock
authors.forename: Riyaz
authors.initials: R
authors.lastname: Basha
authors.forename: Katie
authors.initials: K
authors.lastname: DiPalma
authors.forename: Amy
authors.initials: A
authors.lastname: Anderson
authors.forename: G Jean
authors.initials: GJ
authors.lastname: Harry
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Rice
authors.forename: Bryan
authors.initials: B
authors.lastname: Maloney
authors.forename: Debomoy K
authors.initials: DK
authors.lastname: Lahiri
authors.forename: Nasser H
authors.initials: NH
authors.lastname: Zawia
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000686:Amyloidosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D016329:Sp1 Transcription Factor