|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
We and others have shown that APP C99, the major beta-secretase product, and Abeta are markedly increased in DS.
|
16816112 |
2006 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Moreover, DS fibroblasts and Alzheimer disease cortex also show overexpression of Notch1 and Dll1, indicating that enhanced beta-APP processing found in both DS and AD could be instrumental in these changes.
|
16126912 |
2005 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Elimination of amyloid precursor protein in senile plaques in the brain of a patient with Alzheimer-type dementia and Down syndrome.
|
30086988 |
2019 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
This may be the case during pathological evolution of AD and DS when beta/A4 derived from synaptic APP is converted to beta/A4 amyloid by radical generation.
|
8239320 |
1993 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
These observations suggest that the development of pathological changes in DS brains does not parallel that observed in AD, which might be attributable to different causes in the pathogenesis of betaA4 formation.
|
9928821 |
1999 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
We conclude that ETS2 is a transcriptional regulator of beta-APP and that overexpression of ETS2 in DS may play a role in the pathogenesis of the brain abnormalities in DS and possibly AD.
|
12890557 |
2003 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
The therapeutic value of inhibiting translation of the amyloid precursor protein (APP) offers the possibility to reduce neurotoxic amyloid formation, particularly in cases of familial Alzheimer's disease (AD) caused by APP gene duplications (Dup⁻APP) and in aging Down syndrome individuals.
|
30823541 |
2019 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Subjects affected by Down's syndrome (DS) have an increased APP gene dosage and overexpress APP.
|
8564851 |
1996 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
A four- to fivefold overexpression of the gene for the Alzheimer amyloid precursor protein (APP) in individuals with Down's syndrome (DS) appears to be responsible for the fifty year earlier onset of Alzheimer's disease pathology in DS compared to the normal population.
|
8427604 |
1993 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Down syndrome (DS) patients with chromosome 21 trisomy present AD-like pathologies at earlier ages (40s) compared with sporadic AD patients, because APP gene expression is 1.5-fold higher than that in healthy people, thus causing a 1.5-fold increase in Aβ production.
|
28250274 |
2017 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
The appearance of APP-dependent endosome anomalies in DS beginning in infancy and evolving into the full range of AD-related endosomal-lysosomal deficits provides a unique opportunity to characterize the earliest pathobiology of AD preceding the classical neuropathological hallmarks.
|
28988799 |
2018 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
The demonstration that Ptch1 overexpression in trisomic NPCs is due to an APP fragment provides a link between this trisomic gene and the defective neuronal production that characterizes the DS brain.
|
21266456 |
2011 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Two of the three A beta transgenic strains (APP(NLh) and TgCRND8) exhibited significantly decreased cortical BDNF mRNA levels compared with wild-type mice, whereas neither the other strain (APP(swe)/PS-1) nor the Down syndrome mouse model (Ts65Dn) was affected.
|
19625522 |
2009 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
PosttranslationalModification
|
disease |
BEFREE |
Modern research had proposed that the over expression of DYRK1A (Dual specificity tyrosine phosphorylation regulated kinase1A, a family of protein kinases, positioned within the Down's syndrome critical region (DSCR) on human chromosome 21causes phosphorylation of APP protein resulting in its cleavage to Aβ 40, 42 and tau proteins (regulated by beta and gamma secretase) which plays critical role in early onset of Alzheimer's disease (AD) detected in Down's syndrome (DS), leading to permanent functional and structural deformities which results ultimately into neuro-degeneration and neuronal death.
|
30243157 |
2018 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Transcriptional regulation of the gene encoding the amyloid precursor protein (APP) may play an important role in the formation of the amyloid depositions observed in Alzheimer disease and Down syndrome patients.
|
1851527 |
1991 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
The overall goal of this study was to determine whether APP contributes to neurogenesis impairment in DS by influencing in addition to proliferation, cell fate specification, and neurite development.
|
23740250 |
2013 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
The occurrence of +1 frameshifted proteins, such as amyloid precursor protein (APP+1) and ubiquitin-B (UBB+1) in Down syndrome (DS) has been linked to the onset of Alzheimer's disease (AD).
|
10666673 |
1999 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Furthermore, it is believed that individuals with Down syndrome (DS) have increased APP expression, due to an extra copy of chromosome 21 (Hsa21), that contains the gene for APP.
|
29383688 |
2018 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Genes that are overexpressed in DS (APP, DSCAM, MNB/DYRK1A, and RCAN1) produce proteins critical for neuron and synapse growth, development and maintenance.
|
17361036 |
2007 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Taken together, these results reveal a potential regulatory link between APP and DYRK1A in DS brains, and suggest that the over-expression of DYRK1A in DS may play a role in accelerating AD pathogenesis through phosphorylation of APP.
|
18005339 |
2008 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
The objective of this study was to evaluate amyloid β (Aβ) deposition patterns in different groups of cerebral β amyloidosis: (1) nondemented with amyloid precursor protein overproduction (Down syndrome); (2) nondemented with abnormal processing of amyloid precursor protein (preclinical autosomal dominant Alzheimer disease); (3) presumed alteration in Aβ clearance with clinical symptoms (late-onset AD); and (4) presumed alterations in Aβ clearance (preclinical AD).
|
29477284 |
2018 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
These new mechanistic insights into the role of triplication of genes on chromosome 21, other than APP, in the development of Alzheimer's disease in individuals who have Down syndrome may have implications for the treatment of this common cause of neurodegeneration.
|
29945247 |
2018 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Using carboxyl end-terminal specific antibodies to A beta peptides, we examined the immunocytochemical distribution of A beta 40 and A beta 42 species in brain tissue from a Swedish subject with familial AD (FAD) bearing the double mutation at codons 670/671 in the amyloid beta precursor protein (A beta PP), and from subjects with Down's syndrome and sporadic AD.
|
8856679 |
1996 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Factors which influence Abeta levels, rather than overexpression of APP, may account for the differences in age at onset of dementia in Down's syndrome.
|
11983636 |
2002 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
The focus of Alzheimer's disease (AD) neuroimaging research has shifted towards an investigation of the earliest stages of AD pathogenesis, which manifests in every young adult with Down syndrome (DS; trisomy 21) resulting from a deterministic genetic predisposition to amyloid precursor protein overproduction.
|
29752653 |
2019 |