Decreased Expression of Hippocampal Cholinergic Neurostimulating Peptide Precursor Protein mRNA in the Hippocampus in Alzheimer Disease

Abstract

Hippocampal cholinergic neurostimulating peptide (HCNP) is involved in the phenotype development of the septo-hippocampal system. HCNP precursor protein (HCNP-pp) is known to interact with other molecules including phosphatidylethanolamine and Raf-1 kinase, and is also known as phosphatidylethanolamine-binding protein and raf kinase-inhibitory protein. To assess whether HCNP-pp is involved in the pathogenesis of Alzheimer disease (AD), the expression levels of its mRNA in the hippocampus of autopsy brains from patients with dementia (including AD and ischemic vascular dementia) were compared with those of non-demented control subjects. The in situ hybridization analysis revealed that the expression of HCNP-pp mRNA in patients with clinically late-onset AD was decreased in the hippocampal CA1 field, but not in the CA3 field or the dentate gyrus. The early-onset AD patients showed a wide range of expression levels in the hippocampal sub-regions. Northern blot analysis of HCNP-pp mRNA in brain tissue supported these observations. Since HCNP is known to stimulate the enzymatic activity of choline acetyltransferase in neurons, its low expression in the CAI field of AD patients may explain the downregulation of cholinergic neurons seen in these patients and may thus contribute to the pathogenic processes underlying AD.

Raf Kinase Inhibitory Protein (RKIP): Functional Pleiotropy in the Mammalian Brain

“…63 Consistent with a potential role of HCNP in AD, levels of pebp1 mRNA are suppressed in the CA1 region of the hippocampi of clinically late-onset AD patients relative to nondemented controls. 64 Given previous evidence that shows that AD pathologies are localized in the CA1 region and there is loss of cholinergic fibers innervating the hippocampus, this study suggests that reduced expression of HCNP may contribute to the pathogenesis of AD. In comparison, earlier work showed that the cerebrospinal fluid (CSF) of some early-onset, but not late-onset, AD patients exhibits high levels of HCNP relative to non-AD patients.…”

Raf kinase inhibitory protein knockout mice: Expression in the brain and olfaction deficit

“…The role of RKIP-1 in AD emerges through its diminished expression in affected neurons [14]. An inverse correlation between the severity of AD and the RKIP-1 level in human and mouse brains has been reported [14,24].…”

Raf Kinase Inhibitor Protein Attenuates Ischemic-Induced Microglia Cell Apoptosis and Activation Through NF-κB Pathway

“…For example, RKIP has a variety of physiological functions in brain, including its function in the synaptic plasticity and circadian clock [3]. As a precursor protein of hippocampal cholinergic neurons, RKIP is important to synthesis acetylcholine and develop septal cholinergic neurons for learning and memory [4]. Furthmore, RKIP expression disorders can lead to diabetic nephropathy and Alzheimer’s disease [5].…”