BACKGROUND: Active and passive immunotherapy in both amyloid-beta precursor 
protein (APP) transgenic mice and Alzheimer's Disease (AD) patients have 
resulted in remarkable reductions in amyloid plaque accumulation, although the 
degree of amyloid regression has been highly variable. Nine individuals with a 
clinical diagnosis of AD dementia were actively immunized with the Aβ peptide 
1-42 (AN-1792) and subjected to detailed postmortem biochemical analyses. These 
patients were compared to 6 non-immunized AD cases and 5 non-demented control 
(NDC) cases.
RESULTS: All patients were assessed for the presence of AD pathology including 
amyloid plaques, neurofibrillary tangles and vascular amyloidosis. This effort 
revealed that two immunotherapy recipients had dementia as a consequence of 
diseases other than AD. Direct neuropathological examination consistently 
demonstrated small to extensive areas in which amyloid plaques apparently were 
disrupted. Characterization of Aβ species remnants by ELISA suggested that total 
Aβ levels may have been reduced, although because the amounts of Aβ peptides 
among treated individuals were extremely variable, those data must be regarded 
as tentative. Chromatographic analysis and Western blots revealed abundant 
dimeric Aβ peptides. SELDI-TOF mass spectrometry demonstrated a substantive 
number of Aβ-related peptides, some of them with elongated C-terminal sequences. 
Pro-inflammatory TNF-α levels were significantly increased in the gray matter of 
immunized AD cases compared to the NDC and non-immunized AD groups.
CONCLUSIONS: Immunotherapy responses were characterized by extreme variability. 
Considering the broad range of biological variation that characterizes aging and 
complicates the recognition of reliable AD biomarkers, such disparities will 
make the interpretation of outcomes derived from epidemiologic and therapeutic 
investigations challenging. Although in some cases the apparent removal of 
amyloid plaques by AN-1792 was impressive, proportionate alterations in the 
clinical progression of AD were not evident. The fact that plaque elimination 
did not alter the trajectory of decline into dementia suggests the likelihood 
that these deposits alone are not the underlying cause of dementia.