|
Complete Trisomy 21 Syndrome
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Therefore, (one of) the effects of the mutations in the presenilin 1:PS-1 (S182) gene may be to cause or at least promote an early and excessive deposition of Abeta42(43) within the brain, a property shared with other inherited forms of AD, such as those due to amyloid precursor protein mutations, and Down's syndrome (trisomy 21).
|
8773595 |
1996 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
The 130 to 106-110 kDa APP isoform ratio was similar in young DS and control subjects, and markedly lower in AD patients.
|
12525890 |
2003 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
The overexpression of amyloid precursor protein gene may be sufficient to drive Alzheimer's disease (AD) neuropathology that is observed in virtually all individuals with DS by the age of 40 years.
|
26103884 |
2015 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
These findings suggest that altered cholesterol metabolism and APP trafficking mediated by ABCG1 may contribute to the accelerated onset of AD neuropathology in DS.
|
17293612 |
2007 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Alzheimer's disease (AD) may affect in excess of 90% of individuals with Down syndrome (DS) after age 60, due to duplication of the APP gene in trisomy of chromosome 21, with neuropathology that is comparable to Sporadic AD and Familial AD (FAD).
|
28870521 |
2018 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
In this review we will highlight studies which support a key role for SOD1 and APP in the pathogenesis of neural abnormalities observed in individuals with Down syndrome.
|
10666681 |
1999 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Most individuals with Down syndrome (DS) have three copies of <i>APP</i>, leading to elevated APP expression, increased Aβ deposition, and characteristic AD neuropathology.
|
28003277 |
2017 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
To gain insights into the role of DSCR1 in AD, we explored the functional interaction between DSCR1 and the amyloid precursor protein (APP), which is known to cause AD when duplicated or upregulated in DS.
|
24086147 |
2013 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
There are suggestions that an increase in subcellular processing of APP and factors related to membrane APP cleavage favor the secretion of Abeta with age in DS.
|
17168651 |
2006 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
This is exemplified by CAA observed in APP duplication and Down's syndrome patients, neprilysin polymorphism patients and knockout mice and Swedish APP (KM670/671NL) mice.
|
18184371 |
2008 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Moreover, elevation of APP was associated with a decreased BACE1-mediated processing of CHL1 not only in 12 months old 5XFAD mice but also in human brains from subjects affected by Down syndrome, most likely due to substrate competition.
|
29391027 |
2018 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The presence of this PS1 mutation has an even greater effect on both vascular and parenchymal amyloid deposition, than the overexpression of the amyloid beta precursor protein present in DS patients, suggesting that PS mutations can be a critical factor determining amyloid deposition.
|
9737546 |
1998 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
These data suggest regulation of APP mRNAs is normal in AD and DS PBMC.
|
7478160 |
1995 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Three copies of APP are associated with AD pathology in Down's syndrome and in EOAD, suggesting that overexpression of APP may be a risk factor for LOAD.
|
17427190 |
2007 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Using astrocytes and neuronal cultures from DS fetuses, a recent paper shows that altered metabolism of the amyloid precursor protein and oxidative stress result from mitochondrial dysfunction.1 These findings are consistent with considerable data implicating the role of the mitochondrial genome in DS pathogenesis and aetiology.
|
12210526 |
2002 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Plaque formation was greater in DS and missense APP mutations than in APPdup, sEOAD and sLOAD cases.
|
29770843 |
2018 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
However, because the extra copy of APP leads to increased beta-amyloid peptide (Aβ) accumulation in DS, we hypothesized that there would be more extensive and widespread cerebral amyloid angiopathy (CAA) with age in DS relative to sporadic AD.
|
29195510 |
2017 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Previous evidence obtained in the Ts65Dn mouse model of DS showed that the triplicated gene APP (amyloid precursor protein) is critically involved in neurogenesis alterations.
|
28359846 |
2017 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Aberrant expression of the amyloid precursor protein (APP) gene may contribute to the beta-amyloid deposition seen in Alzheimer's disease and Down syndrome patients.
|
8746452 |
1995 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our findings suggest that genes on the trisomic Ts1Cje segment other than APP and SOD1 can cause oxidative stress, mitochondrial dysfunction and hyperphosphorylation of tau, all of which may play critical roles in the pathogenesis of mental retardation in DS.
|
16891409 |
2006 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
This has led to the hypothesis that sets forth that during the gestation of a baby with DS there is a greater fetomaternal transfer of cells and of products of the genes of chromosome 21--among them, βAPP and its metabolites Aβ40 and Aβ42.
|
21944886 |
2011 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Finally, since APP is over-expressed in Down syndrome individuals because of the extra copy of chromosome 21, in the last section of the review, we discuss the potential contribution of APP to the neuronal and synaptic defects described in this genetic condition.
|
28677143 |
2017 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Increased dosage of amyloid precursor protein in Down syndrome (trisomy 21) predisposes to dementia of Alzheimer type and may also contribute to acute leukemia and transient myeloproliferative disorder.
|
18623069 |
2008 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
Allelic variability in D21S11, but not in APP or APOE, is associated with cognitive decline in Down syndrome.
|
9189907 |
1997 |
|
Complete Trisomy 21 Syndrome
|
0.100 |
Biomarker
|
disease |
BEFREE |
These results highlight DS as a model to understand the role of APOE4 allele in unsuccessful ageing considering that a number of proinflammatory supernumerary genes (Cu/Zn superoxide dismutase, Ets-2 transcription factors, Down syndrome critical region 1, stress-inducible factor, interferon-alpha receptor and the amyloid precursor protein) are located on chromosome 21 and are implied in the pathologic processes of DS.
|
17559337 |
2007 |