title: Chemical and neuropathological analyses of an Alzheimer's disease patient treated with solanezumab.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Clinical Education, Midwestern UniversityGlendale, AZ 85308; Division of Neurobiology, Barrow Neurological InstitutePhoenix, AZ 85013.
authors.forename: Alex E
authors.initials: AE
authors.lastname: Roher
authors.affiliation: Laboratory of Neuropathology, Banner Sun Health Research Institute Sun City, AZ 85351.
authors.forename: Chera L
authors.initials: CL
authors.lastname: Maarouf
authors.affiliation: Department of Microbiology, Midwestern University Glendale, AZ 85308.
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Kokjohn
authors.affiliation: Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute Sun City, AZ 85351.
authors.forename: Christine
authors.initials: C
authors.lastname: Belden
authors.affiliation: Laboratory of Neuropathology, Banner Sun Health Research Institute Sun City, AZ 85351.
authors.forename: Geidy
authors.initials: G
authors.lastname: Serrano
authors.affiliation: Alzheimer's and Memory Disorders Division, Barrow Neurological Institute Phoenix, AZ 85013.
authors.forename: Marwan S
authors.initials: MS
authors.lastname: Sabbagh
authors.affiliation: Laboratory of Neuropathology, Banner Sun Health Research Institute Sun City, AZ 85351.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
keywords: Alzheimer’s disease; amyloid precursor protein; amyloid-beta; cerebral amyloid angiopathy; immunotherapy; solanezumab