Discussion
Solanezumab immunotherapy provided no apparent relief in the clinical evolution of dementia in this particular AD patient, since there was a continuous cognitive deterioration and full expression of amyloid deposition and neuropathology.
Methods
The solanezumab-treated AD case (SOLA-AD) was compared to non-demented control (NDC, n = 5) and non-immunized AD (NI-AD, n = 5) subjects. Brain sections were stained with H&E, Thioflavine-S, Campbell-Switzer and Gallyas methods. ELISA and Western blots were used for quantification of proteins of interest.
Results
The SOLA-AD subject's neuropathology and biochemistry differed sharply from the NDC and NI-AD groups. The SOLA-AD case had copious numbers of amyloid laden blood vessels in all areas of the cerebral cortex, from leptomeningeal perforating arteries to arteriolar deposits which attained the cerebral amyloid angiopathy (CAA) maximum score of 12. In contrast, the maximum CAA for the NI-AD cases averaged a total of 3.6, while the NDC cases only reached 0.75. The SOLA-AD subject had 4.4-fold more soluble Aβ40 and 5.6-fold more insoluble Aβ40 in the frontal lobe compared to NI-AD cases. In the temporal lobe of the SOLA-AD case, the soluble Aβ40 was 80-fold increased, and the insoluble Aβ40 was 13-fold more abundant compared to the non-immunized AD cases. Both soluble and insoluble Aβ42 levels were not dramatically different between the SOLA-AD and NI-AD cohort.