| Abstrakt: |
Alzheimer's disease (AD) was described more than a century ago. However, there are still no effective approaches to its treatment, which may suggest that the search for the cure is not being conducted in the most productive direction. AD begins as selective impairments of declarative memory with no deficits in other cognitive functions. Therefore, understanding of the AD pathogenesis has to include the understanding of this selectivity. Currently, the main efforts aimed at prevention and treatment of AD are based on the dominating hypothesis for the AD pathogenesis: the amyloid hypothesis. But this hypothesis does not explain selective memory impairments since β-amyloid accumulates extracellularly and should be toxic to all types of cerebral neurons, not only to "memory engram neurons." To explain selective memory impairment, I propose the autoimmune hypothesis of AD, based on the analysis of risk factors for AD and molecular mechanisms of memory formation. Memory formation is associated with epigenetic modifications of chromatin in memory engram neurons and, therefore, might be accompanied by the expression of memory-specific proteins recognized by the adaptive immune system as "non-self" antigens. Normally, the brain is protected by the blood-brain barrier (BBB). All risk factors for AD provoke BBB disruptions, possibly leading to an autoimmune reaction against memory engram neurons. This reaction would make them selectively sensitive to tauopathy. If this hypothesis is confirmed, the strategies for AD prevention and treatment would be radically changed. [ABSTRACT FROM AUTHOR] |
