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[F4–02–04]: TRISOMY 21 CAUSES A DEFICIT IN LYSOSOMAL CATHEPSINS AND ALTERS APP/Aβ PROCESSING INDEPENDENTLY OF AN EXTRA COPY OF APP
Author(s) -
Wiseman Frances K.
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.2017.07.381
Subject(s) - trisomy , chromosome 21 , down syndrome , cathepsin b , biology , cathepsin , genetically modified mouse , microbiology and biotechnology , transgene , genetics , gene , chromosome , biochemistry , enzyme
(AD) are present in the brains of nearly all individuals with Down syndrome (DS) after the age of 30, there is considerable variability in age of onset of clinical symptoms. We need a better understanding of the natural history of AD in DS and clinical progression as well as associated biomarkers in order to conduct such trials. Methods: The London Down syndrome consortium has been conducting an in-depth longitudinal cognitive phenotyping study of >400 adults with DS using a variety of cognitive tasks including tests of memory and executive functions (using CANTAB computer tasks and table-top tasks) and symptoms of dementia (using CAMDEX-DS). All participants donated blood or sputum for DNA and genetic analysis. Results: We will present data on the sequence of cognitive decline with aging in DS, clinical predictors of decline, and clinical differences associated with APOE and other genetic markers. Conclusions: Such data may be used to develop reliable cognitive outcome measures and to stratify and plan clinical trials to prevent or delay AD in the DS population. Some of the issues related to conducting clinical trials in this population will be highlighted alongside potential solutions.