Please use this identifier to cite or link to this item: 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

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_3389_fnbeh_2015_00299.pdf432.96 kBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

3
checked on May 13, 2022

Page view(s)

124
checked on May 12, 2022

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons