Hamdan Medical Journal (previously the Journal of Medical Sciences)
|Table of Contents|
Unraveling the Molecular Basis of Alzheimer's Disease Yields Novel Therapies: A Personal Retrospective
Among the myriad disorders that can devastate mental function, the example of Alzheimer's disease looms particularly large for neuroscientists. In part, this is because it is the most common of the brain degenerative diseases. But it is also because it begins with a remarkably pure impairment of cognitive function. Patients with Alzheimer's disease are robbed insidiously of their most human qualities: memory, reasoning, abstraction, insight and language. In the beginning, otherwise healthy individuals experience a subtle and intermittent impairment of their ability to encode new memories, first of trivial and later important episodes of everyday life. The gradual dissolution of the ability to register new details and then retrieve them when needed evolves in an individual whose motor and sensory functions are well preserved. Over a span of many months to several years, first declarative and then nondeclarative memory are eroded, and other complex mental functions such as judgment and planning slowly slip away. But the subtlety of the earliest amnestic symptoms, occurring without clinical evidence of other neural dysfunction, suggest that something is discretely, perhaps intermittently, interrupting the function of synapses that encode new declarative memories. Research conducted over more than two decades suggests that this "something" is the amyloid β-protein (Aβ), a small, hydrophobic peptide with an ominous tendency to assemble into long-lived polymers in regions of the brain that serve memory and cognition. This chapter provides a personal retrospective of work in the author’s laboratory that contributed to this conclusion.
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