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[F4–03–02]: BEHAVIORAL INTERVENTIONS TO PREVENT, DELAY, OR SLOW ALZHEIMER's DISEASE, MILD COGNITIVE IMPAIRMENT, OR AGE‐RELATED COGNITIVE DECLINE
Author(s) -
Butler Mary
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.2017.07.383
Subject(s) - psychological intervention , dementia , cognition , observational study , cognitive decline , psycinfo , randomized controlled trial , medicine , effects of sleep deprivation on cognitive performance , alzheimer's disease , clinical psychology , psychology , disease , gerontology , medline , psychiatry , political science , law
Hsa21 sequences, other thanAPP, cause cysteine cathepsin deficits that result in failure to activate these proteases in DS. We successfully modelled these enzymatic changes in a novel AD-DS mouse model system, and found that they occur independently of gross-enlargement of the endo-lysosomes. Using our AD-DSmousemodel, we show that trisomy of Hsa21 sequences, other thanAPP, also alter themetabolism of APP/Ab. These changes decrease the soluble Ab38/42 ratio and are associated with an increase in Ab aggregation and deposition, and result in exacerbation of APP/Ab-associated hyper-activity and specific deficits in two tests of short-term memory. We also show that the trisomy-associated changes in APP/Ab metabolism we observe occur independently of alterations in a-, bor g-secretase activity or changes in the rate of extracellular Ab-clearance in vivo. Conclusions: We propose that trisomy Hsa21-associated cathepsin deficits are a novel AD-DS pathomechanism that alter APP/Ab processing and may contribute to the development of AD in people who have DS.