アミロイドβタンパク質病理の伝播とAlzheimer病の治療戦略

抄録

It is widely known that prion diseases can be transmitted among individuals, causing serious problems such as iatrogenic prion diseases. Amyloid β protein (Aβ) is deposited in the cerebral parenchyma and blood vessels (cerebral β–amyloidosis), causing dementia and cerebrovascular disease. Cerebral β–amyloidosis is a main pathological change of Alzheimer disease (AD), and a number of experimental studies have been reported that cerebral β–amyloidosis can be transmitted among individuals like prion diseases. Furthermore, several autopsy studies of iatrogenic prion disease reported the possibility of cerebral β–amyloidosis is transmitted by medical procedures. Cerebral amyloid angiopathy (CAA), a deposition of Aβ in cerebral blood vessels, is usually seen in the elderly, but, recently, many cases of young onset CAA–related cerebral hemorrhage had a history of neurosurgical procedures with and without dura mater graft in childhood, suggesting the possibility of transmission of cerebral β–amyloidosis by neurosurgery. As described above, Aβ–CAA could be transmitted among individuals by medical practice, and this condition has recently been termed iatrogenic CAA.

Currently, there is no use of cadaver–derived products for dura mater replacement or growth hormone replacement, and it can be expected that the transmission of cerebral β–amyloidosis associated with cadaver–derived products will be largely prevented. However, case reports of iatrogenic CAA have been increasing year by year. We should develop methods to prevent transmission of cerebral β–amyloidosis by medical procedures and methods to treat the transmitted cerebral β–amyloidosis. We have reported the inhibition of Aβ seeding activity by autoclaving, but the conditions for autoclaving are severe, and it is important to develop a more practical method of inactivating Aβ transmission activity.