Abstract
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.
Highlights
Alzheimer’s disease (AD) is a complex neurodegenerative syndrome caused by abnormal accumulation of biological products for decades
The overall MMSE scores were lower in patients with dementia, while it was in the normal range in mild cognitive impairment (MCI) and healthy control subjects
Recent neuropathological studies have demonstrated that patients with AD have concomitant cerebrovascular pathology[25]
Summary
Alzheimer’s disease (AD) is a complex neurodegenerative syndrome caused by abnormal accumulation of biological products for decades. It has been reported that Notch signaling in cerebrovascular diseases is associated with angiogenesis and the functioning of the blood-brain barrier (BBB)[1]. Notch could mediate neurodegenerative progress including AD. Notch is involved in regulating proteolytic processing of amyloid precursor protein (APP) through cleavage by ADAM10/17 and γ-secretase[2, 3]. The membrane-bound Notch receptor is cleaved into a secreted Notch extracellular truncation domain () and an activated Notch intracellular domain (NICD). Notch signaling cascade is involved in various intracellular signaling processes including BBB functioning, cerebrovascular formation, and the development of tissue-specific cell types[5, 6]. In BBB, during the vessel formation process, vascular
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