Peripheral blood amyloid-β involved in the pathogenesis of Alzheimer's disease via impacting on peripheral innate immune cells.

A key pathological factor of Alzheimer's disease (AD), the most prevalent form of age-related dementia in the world, is excessive β-amyloid protein (Aβ) in extracellular aggregation in the brain. And in the peripheral blood, a large amount of Aβ is derived from platelets. So far, the causality between the levels of peripheral blood Aβ and its aggregation in the brain, particularly the role of the peripheral blood Aβ in the pathology of AD, is still unclear. And the relation between the peripheral blood Aβ and tau tangles of brain, another crucial pathologic factor contributing to the pathogenesis of AD, is also ambiguous. More recently, the anti-Aβ monoclonal antibodies are approved for treatment of AD patients through declining the peripheral blood Aβ mechanism of action to enhance plasma and central nervous system (CNS) Aβ clearance, leading to a decrease Aβ burden in brain and improving cognitive function, which clearly indicates that the levels of the peripheral blood Aβ impacted on the Aβ burden in brain and involved in the pathogenesis of AD. In addition, the role of peripheral innate immune cells in AD remains mostly unknown and the results obtained were controversial. In the present review, we summarize recent studies on the roles of peripheral blood Aβ and the peripheral innate immune cells in the pathogenesis of AD. Finally, based on the published data and our own work, we believe that peripheral blood Aβ plays an important role in the development and progression of AD by impacting on the peripheral innate immune cells.