Targeting the hematopoietic system for the treatment of Alzheimer's disease

Alzheimer's disease (AD) is the most prevalent cause of dementia in humans. This disease is characterized by the presence of amyloid beta (Ab) deposits in the parenchyma (also known as amyloid plaques or senile plaques) and in the cerebral vasculature. Though Ab formation and deposits are strongly correlated with cognitive impairment, the mechanisms responsible for the synaptic dysfunctions and loss of neurons in AD remain largely unknown. Many studies have provided evidence that microglial cells are attracted to amyloid deposits both in human samples and in rodent transgenic models that develop this disease. We have recently found that blood-derived microglia and not their resident counterparts have the ability to eliminate amyloid deposits by a cell-specific phagocytic mechanism. These bone marrow-derived microglia have consequently a great therapeutic potential for AD patients. Molecular strategies aiming to improve their recruitment could lead to a new powerful tool for the elimination of toxic Ab and improve cognitive functions. However, numerous limitations have to be taken into consideration before recommending such a cellular therapy and these are discussed in the present review.