Kadir A, Andreasen N, Almkvist O, Wall A, Forsberg A, Engler H, Hagman G, Lärksäter M, Winblad B, Zetterberg H, Blennow K, Långström B, Nordberg A. 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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Karolinska Institutet
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.
New diagnostics go hand in hand with new therapies. Are we there yet! Roll on the summer months!
View all comments by Gerard RobertsPhenserine 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.
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