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O1‐10‐05: Pharmacodynamics of the Oral Bace Inhibitor JNJ‐54861911 in Early Alzheimer's Disease
Author(s) -
Streffer Johannes,
Börjesson-Hanson Anne,
Van Broeck Bianca,
Smekens Pascale,
Timmers Maarten,
Tesseur Ina,
Tatikola Kanaka,
Russu Alberto,
Sinha Vikash,
Salvadore Giacomo,
Aguilar Miguel,
Frank Anna,
Matias-Guiu Jorge,
Boada Mercè,
Baquero Miquel,
Tritsmans Luc,
Van Nueten Luc,
Andreassen Niels,
Engelborghs Sebastiaan
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.350
Subject(s) - biomarker , pharmacodynamics , medicine , tolerability , placebo , asymptomatic , disease , oncology , pharmacokinetics , dementia , gastroenterology , pathology , adverse effect , biology , biochemistry , alternative medicine
cebo were studied. Comprehensive neuropathological assessments were performed ranging from 4 months to 14 years after the trial. Large coronal paraffin sections of cerebral hemisphere were immunostained for Ab, scanned, then (i) the entire neocortical ribbon was scored for plaques in a CERAD-like manner (frequent1⁄43, moderate1⁄42, sparse1⁄41, none1⁄40) and (ii) false coloured to permit visualisation of staining patterns at low power. Results: 16/21 had a distribution of tangles and at least some residual Ab pathology indicating the cause of dementia had been AD, whereas 5/21 had alternative causes for dementia (PSP1⁄41, DLB1⁄41, VaD1⁄41and FTDTDP431⁄42). 18/21 had received the active agent and 3/21 the placebo. Scanning and false colouration of large Ab immunostained sections generated images suitable for comparison with amyloid PET scans as used in current immunotherapy trials. 13/15 AD subjects receiving the active agent had evidence of plaque removal (almost complete removal1⁄45, extensive patches of removal1⁄44, small patches of removal1⁄44, no plaque removal1⁄42). In the immunised AD group the mean plaque score was 1.46 (range1⁄40.05-2.9) vs. 2.4 for the single placebo AD case. There was a significant inverse correlation between peripheral blood anti-Ab titres and plaque scores. Conclusions: AD patients actively immunised against Ab can remain virtually plaque–free for up to 14 years. Nearly a quarter of the patients examined in this study did not have neuropathologically verified AD. Neuropathology follow up of patients in therapeutic trials for AD provides valuable information on the cause of dementia and effects of treatment.