BMP9 ameliorates amyloidosis and the cholinergic defect in a mouse model of Alzheimer’s disease

Significance Bone morphogenetic protein 9 (BMP9) is a trophic factor for basal forebrain cholinergic neurons (BFCN) and constitutes a candidate therapeutic molecule for diseases characterized by BFCN dysfunction. A prominent example of such an illness, for which effective therapies are critically needed, is Alzheimer’s disease (AD). A decline in BFCN function and diminished cholinergic marker expression occurs in brains of patients with AD and is observed in AD animal models. We report that BMP9 administration is effective in reducing the amyloid plaque burden, reversing cholinergic neuron abnormalities, and generating a neurotrophic milieu for cholinergic neurons in a mouse model of AD, thus providing evidence that the BMP9-signaling pathway may constitute a novel therapeutic target in AD.