Imatinib treatment and Aβ42 in humans.

BACKGROUND

The first-line treatment in chronic myeloid leukemia (CML), imatinib, has been shown to decrease the production of amyloid-β (Aβ) in vitro and in animal studies. However, whether imatinib has this effect in humans is not known.

METHODS

Plasma levels of Aβ42 were analyzed in sequential samples from CML patients treated with imatinib (n=51). The effect of imatinib on Aβ production was also investigated in human embryonic kidney 293 (HEK293) cells overexpressing the amyloid precursor protein (APP) with the Swedish mutation, in mouse primary cortical neurons and in human Down syndrome embryonic stem-cell-derived cortical neurons.

RESULTS

Twelve months of imatinib treatment did not lower plasma Aβ42 levels in CML patients, and imatinib treatment did not lead to less Aβ42 production in any of the in vitro models whereas β- and γ-secretase inhibitors did.

CONCLUSION

These data question the previously described role of imatinib in inhibiting amyloidogenic APP processing and as a drug candidate for AD.