Decreased expression of hippocampal cholinergic neurostimulating peptide precursor protein mRNA in the hippocampus in Alzheimer disease.
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.
Maki
Mina
M
Second Department of Internal Medicine, Medical School, Nagoya City University, Japan.
Matsukawa
Noriyuki
N
Yuasa
Hiroyuki
H
Otsuka
Yasushi
Y
Yamamoto
Takayuki
T
Akatsu
Hiroyasu
H
Okamoto
Takashi
T
Ueda
Ryuzo
R
Ojika
Kosei
K
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
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