Affiliations: BioCircuits Institute, University of California San Diego, La Jolla, CA, USA
Correspondence:
[*]
Correspondence to: Yuri I. Arshavsky, BioCircuits Institute, University of California, San Diego, La Jolla, CA 92093-0402, USA. Tel.: +1 858 822 2010; Fax: +1 858 534 7664; E-mail: yarshavs@ucsd.edu.
Abstract: Alzheimer's disease is a neurodegenerative disease whose sole initial symptom is memory impairment. However, the mechanisms which make the neurons involved in learning and memory particularly vulnerable to the formation of amyloid plaques and neurofibrillary tangles remain completely unknown. Here, I propose a hypothesis that may resolve this puzzle. A growing body of evidence suggests that memory formation involves epigenetic mechanisms that regulate patterns of gene expression. Therefore, it is conceivable that the process of memory consolidation may include the synthesis of novel proteins that are recognized by the immune system as "non-self" antigens. Normally, neurons involved in formation and storage of memory are isolated from the organism's immune system by the blood-brain barrier. Since all known genetic and environmental risk factors for Alzheimer's disease can compromise this barrier, I hypothesize that the disease is initiated as an autoimmune reaction against the memory-bearing neurons. This reaction gradually makes these neurons vulnerable to the subsequent formation of amyloid plaques and neurofibrillary tangles. This hypothesis suggests that early therapy of Alzheimer's disease could be devoted to preventing impairments in the blood-brain barrier. Recent evidence that formation of the blood-brain barrier is controlled via the Wnt/β-catenin signaling pathway may suggest potential directions to addressing this problem.
