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This Month in Archives of Neurology
January 2003

This Month in Archives of Neurology

Arch Neurol. 2003;60(1):14-15. doi:10.1001/archneur.60.1.14

In a climate of heightened concern about biological and chemical terrorism, the neurologist needs to be aware of the potential agents that may be employed. This article focuses on likely substances that may be encountered, including cyanide, cholinesterase inhibitors, botulinum toxin, and anthrax, because of their prominent neurologic manifestations. Martin and Adams have provided an important set of guidelines for the physician by reviewing specific weapons applications, clinical manifestations, and therapies that must be rapidly and accurately applied.

CYP46, the gene encoding cholesterol 24-hydroxylase, plays a key role in the hydroxylation of cholesterol synthesized by the brain and its subsequent transport from the brain. Papassotiropoulos and colleagues have studied a single-nucleotide polymorphism of CYP46 and show that it is associated with increased β-amyloid load in brain tissues as well as with increased cerebrospinal fluid levels of both β-amyloid peptides (Aβ42) and phosphorylated tau protein. They find that this CYP46 polymorphism is associated with a higher risk for late-onset sporadic Alzheimer disease (AD) in 2 independent populations. Thus, rates of synthesis of 24-hydroxyl-cholesterol and its egress from the brain directly influence the biochemical events associated with the pathogenesis of AD. This newly described polymorphism and brain levels of 24-hydroxy-cholesterol are important new issues to be considered in understanding the molecular causes of AD.