. Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease. Ann Neurol. 2008 May;63(5):621-31. PubMed.

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  1. This is the first time an amyloid imaging ligand such as PIB has been used in the evaluation of a drug treatment study in mild AD patients. This is a double-blind study. It shows that in phenserine-treated AD patients, there is in some patients a reduction in PIB retention after three months of up to 15 percent that is more than the test-retest value (less than 5 percent). Interestingly enough, there is an increase in CSF Aβ40 in the phenserine-treated AD patients, and there is a negative correlation between CSF Aβ40 and PIB retention. This indicates that there seems to be a reciprocal change in amyloid in brain versus CSF in the individual patients.

    There is also a correlation between CSF Aβ40 and cognition, as well as with cerebral glucose metabolism. This is promising in that PIB can be useful in the further evaluation of anti-amyloid drug therapy in AD, including immunization therapy.

  2. Phenserine is a unique compound including both cholinesterase- and APP synthesis-inhibitory properties. This publication presents several original first-time features: first, it evaluates a new molecule with potential anti-amyloid properties by directly measuring Aβ levels in brain; secondly, it correlates Aβ brain levels with CSF levels of Aβ; and thirdly, it correlates Aβ levels in brain with glucose metabolism. From these data a profile of a novel CHEI emerges with amyloid-lowering properties in AD. In addition, intriguing correlations among CSF Aβ1-40, cognition, and brain glucose metabolism are shown for the first time. The study clearly demonstrates the value of the PET scan technique in evaluating drugs for AD treatment.