The nuclear factor-kappaB (NF-kappaB) signal transduction pathway regulates several vital cellular processes. During our studies of the glycoproteins involved in Alzheimer disease (AD), we found a significant increase of a 45-kDa protein band that was stained by lectin Maackia amurensis agglutinin (MAA). Mass spectrometry and Western blot analyses indicated that this 45-kDa MMA-positive protein was an inhibitor of NF-kappaB, IkappaBgamma. By Western blot analysis, the levels of both IkappaBgamma and NF-kappaB precursor, p105, were found to be elevated in AD brain as compared to age-matched controls. Our findings suggest that the NF-kappaB pathway might be involved in the molecular mechanism of AD.