title: Intranasal BMP9 Ameliorates Alzheimer Disease-Like Pathology and Cognitive Deficits in APP/PS1 Transgenic Mice.
abstract: Alzheimer's disease (AD) is the most common type of dementia and has no effective therapies. Previous studies showed that bone morphogenetic protein 9 (BMP9), an important factor in the differentiation and phenotype maintenance of cholinergic neurons, ameliorated the cholinergic defects resulting from amyloid deposition. These findings suggest that BMP9 has potential as a therapeutic agent for AD. However, the effects of BMP9 on cognitive function in AD and its underlying mechanisms remain elusive. In the present study, BMP9 was delivered intranasally to 7-month-old APP/PS1 mice for 4 weeks. Our data showed that intranasal BMP9 administration significantly improved the spatial and associative learning and memory of APP/PS1 mice. We also found that intranasal BMP9 administration significantly reduced the amyloid β (Aβ) plaques overall, inhibited tau hyperphosphorylation, and suppressed neuroinflammation in the transgenic mouse brain. Furthermore, intranasal BMP9 administration significantly promoted the expression of low-density lipoprotein receptor-related protein 1 (LRP1), an important membrane receptor involved in the clearance of amyloid β via the blood-brain barrier (BBB), and elevated the phosphorylation levels of glycogen synthase kinase-3β (Ser9), which is considered the main kinase involved in tau hyperphosphorylation. Our results suggest that BMP9 may be a promising candidate for treating AD by targeting multiple key pathways in the disease pathogenesis.
authors.affiliation: Department of Neurology, Jinshan Hospital, Fudan University Shanghai, China.
authors.forename: Zigao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Tinglin Hospital Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Neurology, Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wan
authors.affiliation: Department of Neurology, Jinshan Hospital, Fudan University Shanghai, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Duan
authors.affiliation: Department of Neurology, Jinshan Hospital, Fudan University Shanghai, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Neurology, Jinshan Hospital, Fudan University Shanghai, China.
authors.forename: Hengbing
authors.initials: H
authors.lastname: Zu
keywords: Alzheimer’s disease; amyloid β; bone morphogenetic protein 9; glycogen synthase kinase-3β; low-density lipoprotein receptor-related protein 1; neuroinflammation; tau