Noggin rescues age-related stem cell loss in the brain of senescent mice with neurodegenerative pathology

Significance Alzheimer’s disease (AD) is the most common cause of age-related neurodegeneration. Damage initially occurs in the hippocampus, a neurogenic brain region essential in forming memories. Since there is no cure for AD, therapeutic strategies that may aid to slow hippocampal dysfunction are necessary. We describe the precocious hippocampal stem cell loss of a mouse model that mimics the onset of pathological AD-like neurodegeneration. The loss is due to an increase in BMP6 that limits neurogenesis. We demonstrate that blocking BMP signaling by means of Noggin administration is beneficial to the hippocampal microenvironment, restoring stem cell numbers, neurogenesis, and behavior. Our findings support further development of BMP antagonists into translatable molecules for the rescue of stem cells and neurogenesis in neurodegeneration/aging.