Chemical and neuropathological analyses of an Alzheimer’s disease patient treated with solanezumab

American Journal of Neurodegenerative Disease

Alex E Roher¹ 

关键词: Alzheimer’;    s disease;    immunotherapy;    solanezumab;    amyloid-beta;    amyloid precursor protein;    cerebral amyloid angiopathy;   

DOI  :  

学科分类：精神健康和精神病学

来源: e-Century Publishing Corporation

【 摘 要 】

Introduction: Based on the amyloid cascade hypothesis of Alzheimer’s disease (AD) pathogenesis, a series of clinical trials involving immunotherapies have been undertaken including infusion with the IgG1 monoclonal anti-Aβ antibody solanezumab directed against the middle of the soluble Aβ peptide. In this report, we give an account of the clinical history, psychometric testing, gross and microscopic neuropathology as well as immunochemical quantitation of soluble and insoluble Aβ peptides and other proteins of interest related to AD pathophysiology in a patient treated with solanezumab. Materials and 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. 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.

【 授权许可】

CC BY-NC