Preventive and therapeutic reduction of amyloid deposition and behavioral impairments in a model of Alzheimer's disease by whole blood exchange

Alzheimer's disease (AD) is the major form of dementia in the elderly population. The main neuropathological changes in AD patients are neuronal death, synaptic alterations, brain inflammation, and the presence of cerebral protein aggregates in the form of amyloid plaques and neurofibrillary tangles. Compelling evidence suggests that the misfolding, aggregation, and cerebral deposition of amyloid-beta (A ss) plays a central role in the disease. Thus, prevention and removal of misfolded protein aggregates is considered a promising strategy to treat AD. In the present study, we describe that the development of cerebral amyloid plaques in a transgenic mice model of AD (Tg2576) was significantly reduced by 40-80% through exchanging whole blood with normal blood from wild type mice having the same genetic background. Importantly, such reduction resulted in improvement in spatial memory performance in aged Tg2576 mice. The exact mechanism by which blood exchange reduces amyloid pathology and improves memory is presently unknown, but measurements of A ss in plasma soon after blood exchange suggest that mobilization of A ss from the brain to blood may be implicated. Our results suggest that a target for AD therapy may exist in the peripheral circulation, which could open a novel disease-modifying intervention for AD.

Automated summary

Alzheimer's disease is the major form of dementia in the elderly, characterized by neuronal death, synaptic alterations, brain inflammation, and the presence of protein aggregates. Exchanging blood with normal mice can reduce amyloid plaques and improve spatial memory in AD mice, suggesting a potential peripheral target for AD therapy.