Altered expression of Notch1 in Alzheimer's disease

• Published in: PloS one 2019-11, Vol.14 (11), p.e0224941
• Main Authors: Cho, Sun-Jung, Yun, Sang-Moon, Jo, Chulman, Jeong, Jihyun, Park, Moon Ho, Han, Changsu, Koh, Young Ho
• Format: Article
• Language: English
• Subjects: ADAM10 Protein - genetics; ADAM10 Protein - metabolism; Advertising executives; Age; Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Angiogenesis; Biology and Life Sciences; Brain; Brain diseases; Case-Control Studies; Cell interactions; Cognitive ability; Dementia; Dementia - metabolism; Dementia disorders; Down syndrome; EDTA; Endothelial cells; Endothelium; Family; Female; Gene expression; Geriatrics; Health risks; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Hypoxia; Induced Pluripotent Stem Cells - metabolism; Ischemia; Levels; Male; Medicine and Health Sciences; Messenger RNA; Microvasculature; Middle Aged; mRNA; Neurodegenerative diseases; Neurons; Neurons - metabolism; Neurosciences; Notch1 protein; Plasma; Plasma levels; Receptor, Notch1 - blood; Receptor, Notch1 - genetics; Receptor, Notch1 - metabolism; Receptors; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signaling; Vascular endothelial growth factor
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0224941

Notch signaling is an evolutionarily conserved pathway that regulates cell-cell interactions through binding of Notch family receptors to their cognate ligands. Notch signaling has an essential role in vascular development and angiogenesis. Recent studies have reported that Notch may be implicated in Alzheimer's disease (AD) pathophysiology. We measured the levels of soluble Notch1 (sNotch1) in the plasma samples from 72 dementia patients (average age 75.1 y), 89 subjects with amnestic mild cognitive impairment (MCI) (average age 73.72 y), and 150 cognitively normal controls (average age 72.34 y). Plasma levels of sNotch1 were 25.27% lower in dementia patients as compared to healthy control subjects. However, the level of Notch1 protein was significantly increased in human brain microvascular endothelial cells (HBMECs) after amyloid-beta treatment. Also, Notch1 mRNA level was significantly increased in HBMECs and iPSC-derived neuronal cells from AD patient compared to normal control. These results indicate that altered expression of Notch1 might be associated with the risk of Alzheimer's disease.