{'fraction_non_alphanumeric': 0.03825503355704698, 'fraction_numerical': 0.010738255033557046, 'mean_word_length': 6.273170731707317, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Alzheimer Disease–Associated Peptide, Amyloid &bgr;40, Inhibits Vascular Regeneration With Induction of Endothelial Autophagy

Objective—Although the majority of cases of Alzheimer disease (AD) are known to be attributable to the sporadic (nongenetic) form of the disease, the mechanism underlying its cause and progression still remains unclear. Methods and Results—We found that vascular &bgr;-amyloid (A&bgr;), A&bgr;40, inhibited the proliferative activity of human brain vascular endothelial cells (HBECs) without toxic effects on them. This peptide also inhibited tube formation and migration of HBECs. Moreover, A&bgr;40 inhibited ex vivo hippocampal revascularization, reendothelialization, and the differentiation of adult endothelial progenitor cells. Importantly, A&bgr;40 suppressed the proliferative activity of HBECs through the induction of “self-digesting” autophagy. This induction involved the intracellular regulation of class 3 phosphatidylinositol 3-kinase (PI3K) as well as Akt signaling in HBECs. Furthermore, tissue culture of murine brain sections from GFP-LC3 transgenic mice revealed that A&bgr;40 not only reduced the vessel density in hippocampal lesions, but also induced autophagy in neurovascular ECs. Conclusions—Our present findings indicate that the initial progression of AD might be in part driven by A&bgr;40-induced endothelial autophagy and impairment of neurovascular regeneration, suggesting important implications for therapeutic approaches to AD.