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[P3–035]: THE REPEATABLE BATTERY FOR THE ASSESSMENT OF NEUROPSYCHOLOGICAL STATUS (RBANS) AS A USEFUL OUTCOME MEASURE IN PRODROMAL AD TRIALS
Author(s) -
Negash Selam,
Ropacki Michael T.,
Weber Christopher J.,
Stein Lisa,
Prochnik Elisabeth,
Randolph Christopher
Publication year - 2017
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.2017.06.1848
Subject(s) - repeatable battery for the assessment of neuropsychological status , clinical endpoint , population , clinical trial , randomized controlled trial , neurocognitive , medicine , surrogate endpoint , psychology , neuropsychology , psychiatry , cognition , environmental health
Until now, no curative treatment is accessible. During the last years, our group designed all D-enantiomeric peptides, with the effort to capture toxic amyloid-beta (Ab) species. Here, we investigated the therapeutic in vivo efficacy of a newly developed D-enantiomeric peptide in old APP/PS1 animals at an age, when they have developed already a full blown amyloid pathology and in pyroglutamate-Ab expressing TBA2.1 mice, which are characterized by a motoric phenotype.Methods:Aged male APP/PS1 mice were orally treated with placebo or 200mg/kg peptide for 3 months. Homozygous TBA2.1 mice and non-transgenic littermates were treated with placebo, 20 mg/kg or 100 mg/kg peptide orally for 3 months. After treatment, mice were tested in different general, cognitive (APP/PS1) and motoric (TBA2.1) behavioural tests (Morris Water Maze, Open field test, SHIRPA test battery). Brains were analysed for changes in amyloid pathology, inflammation and neurodegeneration (histological and biochemical). Results:Analysis of general behavioural tests resulted in no difference in behaviour of treated mice in comparison to non-transgenic littermates. After peptide treatment, APP/PS1 mice showed a significant improved cognitive performance in the Morris Water Maze compared to placebo controls (p 1⁄4 0,05). Treated TBA2.1 mice revealed a significant lower SHIRPA-Score than non-treated littermates, indicating an improvedmotoric phenotype. APP/PS1mice exhibited a significant decrease in plaque burden in the cortex. Treated non-transgenic littermates showed no abnormalities due to treatment with the peptide. Conclusions:We were able to show that the D-enantiomeric peptide has a truly curative effect on cognitive performance, motoric phenotype and plaque load in both mouse models without side effects on behaviour. These results qualify the peptide as promising candidate for the treatment of AD.