From Dark to Bright to Gray Sides of Memory: In Search of its Molecular Basis & Alzheimer’s Disease

Memory is one of the most fascinating functions of the brain. Without it, the human being condition would be lost. Therefore, alterations of memory are at the center of research. In this review, the most prominent memory case disorders are examined to identify basic differences and commonalities of the memory processes altered in the human brain. Then, relevant aspects of the molecular mechanism of memory between Aplysia, Drosophila, and mammals (mice) are highlighted in order to understand the biological aspect of memory in humans. The convergence of both topics provides a foundation for an integrative study of prevention and loss of memory in familial Alzheimer’s disease (FAD). Therefore, we propose that highly superior autobiographical memory (HSAM) and familial Alzheimer’s disease (FAD) are opposite extreme cases of “normal” memory and that their pathophysiology can be explained by changes in protein expression of the PKA / CREB-1 / CPEB axis. We also propose that Aβ directly intermingles with the CPEB. As a result of “yin-yang” prion-like protein interactions, Aβ is capable of interfering with the CPEB’s normal function. If validated, this hypothesis may help explain why anti-amyloid therapies have been negative or inconclusive so far. Therefore, therapies targeting intracellular Aβ oligomers are urgently needed. Molecular studies on HSAM individuals might be invaluable to discover molecules to increase memory skills in FAD.