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https://doi.org/10.3389/fnbeh.2015.00299
Title: | Inter-dependent mechanisms behind cognitive dysfunction, vascular biology and Alzheimer’s dementia in down syndrome: Multi-faceted roles of APP | Authors: | Nizetic, D Chen, C.L Hong, W Koo, E.H |
Keywords: | amyloid beta protein[1-40] amyloid beta protein[1-42] amyloid precursor protein calcium channel L type cyclin dependent kinase 5 ephrin receptor B2 Fc receptor IIb gamma secretase high density lipoprotein n methyl dextro aspartic acid prion protein sorting nexin sorting nexin 27 tau protein triacylglycerol unclassified drug Alzheimer disease Article binding affinity cell activity chromosome 21 cognition cognitive defect dendritic spine Down syndrome human lipid metabolism mild cognitive impairment nerve cell nerve cell plasticity nonhuman partial trisomy pathogenesis prevalence protein expression protein function protein secretion signal transduction vascular amyloidosis vascular biology |
Issue Date: | 2015 | Citation: | Nizetic, D, Chen, C.L, Hong, W, Koo, E.H (2015). Inter-dependent mechanisms behind cognitive dysfunction, vascular biology and Alzheimer’s dementia in down syndrome: Multi-faceted roles of APP. Frontiers in Behavioral Neuroscience 9 (DEC) : 299. ScholarBank@NUS Repository. https://doi.org/10.3389/fnbeh.2015.00299 | Rights: | Attribution 4.0 International | Abstract: | People with Down syndrome (DS) virtually all develop intellectual disability (ID) of varying degree of severity, and also have a high risk of early Alzheimer’s disease (AD). ID prior to the onset of dementia, and its relationship to the onset of dementia in DS is a complex phenomenon influenced by many factors, and scarcely understood. Unraveling the causative factors and modulators of these processes remains a challenge, with potential to be informative for both ID and AD, for the development of early biomarkers and/or therapeutic approaches. We review the potential relative and inter-connected roles of the chromosome 21 gene for amyloid precursor protein (APP), in both pathological conditions. Rare non-DS people with duplication of APP (dupAPP) get familial early onset AD (FEOAD) with virtually 100% penetrance and prominent cerebrovascular pathology, but don’t suffer from ID before dementia onset. All of these features appear to be radically different in DS. On the other hand, rare individuals with partial trisomy 21 (T21) (with APP, but not DS-critical region in trisomy) have been described having ID. Likewise, partial T21 DS (without APP trisomy) show a range of ID, but no AD pathology. We review the multi-faceted roles of APP that might affect cognitive functioning. Given the fact that both A? secretion and synaptic maturation/plasticity are dependent on neuronal activity, we explore how this conflicting inter-dependency might affect cognitive pathogenesis in a dynamic way in DS, throughout the lifespan of an individual. © 2015 Nizetic, Chen, Hong and Koo. | Source Title: | Frontiers in Behavioral Neuroscience | URI: | https://scholarbank.nus.edu.sg/handle/10635/181414 | ISSN: | 16625153 | DOI: | 10.3389/fnbeh.2015.00299 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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