Alzheimer Disease and Cellular Mechanisms of Memory Storage

作者：Arshavsky Yuri I^*

来源：Journal of Neuropathology and Experimental Neurology, 2014, 73(3): 192-205.

DOI：10.1097/NEN.0000000000000043

• Alzheimer disease
• Autoimmune reaction
• Blood-brain barrier
• Cerebral amyloid angiopathy
• Memory
• Epigenetics
• Risk factors

Most ongoing efforts to combat Alzheimer disease (AD) are focused on treating its clinical symptoms, but the neuropathologic changes underlying AD appear decades earlier and become essentially irreversible by the time the disease reaches its clinical stages. This necessitates treating AD at preclinical stages, which requires a better understanding of the primary mechanisms leading to AD pathology. Here I argue that such an understanding calls for addressing perhaps the most puzzling question in ADwhy the underlying pathology selectively impairs neurons that are involved in memory formation and storage. Memory formation is associated with epigenetic chromatin modifications and may, therefore, be accompanied by the synthesis of proteins unique to neurons involved in memory. These proteins could be recognized by the immune system as nonself antigens. This does not happen in the healthy brain because of its isolation from the immune system by the blood-brain barrier (BBB). All risk factors for AD impair the BBB, which may allow the immune system to attack memory-involved neurons and make them vulnerable to AD-associated pathology. This hypothesis is testable and, if confirmed, could redirect therapeutic efforts toward maintaining BBB integrity people belonging to AD risk groups rather than treating them when it is too late.

• 出版日期2014-3