The Role of Reelin Signaling in Alzheimer's Disease

Alzheimer's disease (AD) is the most common causes of age-related dementia. It is characterized by the deposition of amyloid-beta peptide and neurofibrillary tangles, as well as neuronal death and synaptic loss. Reelin is an extracellular glycoprotein which performs diverse roles in the developing and adult brain, including regulation of neuronal migration, dendritogenesis, synapse development, hippocampal synaptic plasticity, and learning and memory. Altered expression and glycosylation patterns of Reelin in cerebrospinal and cortical extracts have been reported in AD. Accumulating studies have investigated the molecular mechanism by which Reelin, its receptors, and downstream signaling proteins may contribute to the pathophysiology of AD. However, the molecular mechanisms by which Reelin and its downstream signal transduction contribute to the pathogenesis of AD remain still largely unknown. In the present review, we briefly summarize the current knowledge and recent findings related to the molecular link between Reelin dysfunction and AD-related neuropathology.