title: 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.
authors.affiliation: Second Department of Internal Medicine, Medical School, Nagoya City University, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Maki
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Matsukawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yuasa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Otsuka
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Akatsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamoto
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
authors.forename: Kosei
authors.initials: K
authors.lastname: Ojika
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000727:Androgen-Binding Protein; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D049488:Phosphatidylethanolamine Binding Protein; D049294:Phospholipid Transfer Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D000727:Androgen-Binding Protein; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; D049294:Phospholipid Transfer Proteins; D012333:RNA, Messenger