Affiliations: [a] Neurotoxicology and Epigenomics Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA | [b] National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA | [c] Laboratory of Molecular Neurogenetics, Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, 791 Union Drive, Indianapolis, IN 46202, USA | [d] Maine Department of Health and Human Services, 11 State House Station, Augusta, ME 04333, USA
Correspondence:
[*]
Corresponding author: Nasser H. Zawia, Ph.D., Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA. Tel.: +1 401 874 5909; Fax: +1 401 874 5787; E-mail: nzawia@uri.edu.
Abstract: 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.
