|
rs781049584
|
|
Alzheimer's Disease
|
|
0.080 |
GeneticVariation
|
BEFREE |
Neurons from mutant hiPSC lines express PSEN1-A246E mutations themselves and show AD-like biochemical features, that is, amyloidogenic processing of amyloid precursor protein (APP) indicated by an increase in β-amyloid (Aβ)42/Aβ40 ratio.
|
25027006 |
2014 |
|
rs781049584
|
|
Alzheimer's Disease
|
|
0.080 |
GeneticVariation
|
BEFREE |
Previously, we have documented that prenatal hypoxia can aggravate the cognitive impairment and Alzheimer's disease (AD) neuropathology in APP(Swe) /PS1(A246E) (APP/PS1) transgenic mice, and valproic acid (VPA) can prevent hypoxia-induced down-regulation of β-amyloid (Aβ) degradation enzyme neprilysin (NEP) in primary neurons.
|
24289518 |
2014 |
|
rs781049584
|
|
Alzheimer's Disease
|
|
0.080 |
GeneticVariation
|
BEFREE |
Moreover, blockade of gap junction hemichannel also significantly improved memory impairments without altering amyloid β deposition in double transgenic mice expressing human amyloid precursor protein with K595N and M596L mutations and presenilin 1 with A264E mutation as an Alzheimer's disease mouse model.
|
21712989 |
2011 |
|
rs781049584
|
|
Alzheimer's Disease
|
|
0.080 |
GeneticVariation
|
BEFREE |
Susceptibility to diet-induced obesity and glucose intolerance in the APP (SWE)/PSEN1 (A246E) mouse model of Alzheimer's disease is associated with increased brain levels of protein tyrosine phosphatase 1B (PTP1B) and retinol-binding protein 4 (RBP4), and basal phosphorylation of S6 ribosomal protein.
|
21538175 |
2011 |
|
rs781049584
|
|
Alzheimer's Disease
|
|
0.080 |
GeneticVariation
|
BEFREE |
We also introduced the human Abeta(42) monomer gene vaccine into AD double transgenic mice APPswe/PSEN1(A246E).
|
15596606 |
2004 |
|
rs781049584
|
|
Alzheimer's Disease
|
|
0.080 |
GeneticVariation
|
BEFREE |
Transgenic mice carrying both the human amyloid precursor protein (APP) with the Swedish mutation and the presenilin-1 A246E mutation (APP/PS1 mice) develop Alzheimer's disease-like amyloidbeta protein (Abeta) deposits around 9 months of age.
|
14678749 |
2003 |
|
rs781049584
|
|
Alzheimer's Disease
|
|
0.080 |
GeneticVariation
|
BEFREE |
No detectable influence of neuronal hCOX-2 on AD neuropathology was found in the brain of APPswe/PS1-A246E/hCOX-2 triple-transgenic mice, compared to double APPswe/PS1-A246E.
|
11959394 |
2002 |
|
rs781049584
|
|
Alzheimer's Disease
|
|
0.080 |
GeneticVariation
|
BEFREE |
Transgenic mice expressing human APPswe and PS1-A264E mutations mimic certain neuropathological features of Alzheimer's disease (AD).
|
12101040 |
2002 |
|
rs781049584
|
|
Familial Alzheimer Disease (FAD)
|
|
0.040 |
GeneticVariation
|
BEFREE |
We validated our findings in Ca(2+) imaging experiments with primary fibroblasts obtained from an FAD patient possessing mutant PS1-A246E.
|
17431506 |
2007 |
|
rs781049584
|
|
Familial Alzheimer Disease (FAD)
|
|
0.040 |
GeneticVariation
|
BEFREE |
Co-expression of a human presenilin-1 (PS1) transgene containing the A246E FAD mutation accelerates deposition and also favors-at least initially-accumulation of A beta(42) so that the A beta(2):A beta(40) ratio of peptides from 7- to 12-month-old APP695SWE x PS1A246E animals is significantly elevated above that observed throughout the lifetime of APP695SWE mice.
|
15312963 |
2004 |
|
rs781049584
|
|
Familial Alzheimer Disease (FAD)
|
|
0.040 |
GeneticVariation
|
BEFREE |
We now report that both human wild-type and A246E PS1 efficiently rescue the phenotypes observed in PS1(-/-) embryos, findings consistent with the view that FAD-linked PS1 mutants retain sufficient normal function during mammalian embryonic development.
|
9539132 |
1998 |
|
rs781049584
|
|
Familial Alzheimer Disease (FAD)
|
|
0.040 |
GeneticVariation
|
BEFREE |
In this report, we demonstrate that transgenic animals that coexpress a FAD-linked human PS1 variant (A246E) and a chimeric mouse/human APP harboring mutations linked to Swedish FAD kindreds (APP swe) develop numerous amyloid deposits much earlier than age-matched mice expressing APP swe and wild-type Hu PS1 or APP swe alone.
|
9354339 |
1997 |
|
rs781049584
|
|
Senile Plaques
|
|
0.020 |
GeneticVariation
|
BEFREE |
Valproic acid reduces neuritic plaque formation and improves learning deficits in APP(Swe) /PS1(A246E) transgenic mice via preventing the prenatal hypoxia-induced down-regulation of neprilysin.
|
24289518 |
2014 |
|
rs781049584
|
|
Senile Plaques
|
|
0.020 |
GeneticVariation
|
BEFREE |
In the present study we demonstrated that repeated hypoxia increased beta-amyloid (Abeta) generation and neuritic plaques formation by elevating beta-cleavage of APP in APP(swe)+PS1(A246E) transgenic mice.
|
18063223 |
2009 |
|
rs781049584
|
|
Impaired cognition
|
|
0.010 |
GeneticVariation
|
BEFREE |
Previously, we have documented that prenatal hypoxia can aggravate the cognitive impairment and Alzheimer's disease (AD) neuropathology in APP(Swe) /PS1(A246E) (APP/PS1) transgenic mice, and valproic acid (VPA) can prevent hypoxia-induced down-regulation of β-amyloid (Aβ) degradation enzyme neprilysin (NEP) in primary neurons.
|
24289518 |
2014 |
|
rs781049584
|
|
Frontotemporal dementia
|
|
0.010 |
GeneticVariation
|
BEFREE |
Here we have tested ten major inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia-linked mutants for ATPase activity and found that all have increased activity over the wild type, with one mutant, p97(A232E), having three times higher activity.
|
22270372 |
2012 |
|
rs781049584
|
|
Pick Disease of the Brain
|
|
0.010 |
GeneticVariation
|
BEFREE |
Here we have tested ten major inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia-linked mutants for ATPase activity and found that all have increased activity over the wild type, with one mutant, p97(A232E), having three times higher activity.
|
22270372 |
2012 |
|
rs781049584
|
|
Osteitis Deformans
|
|
0.010 |
GeneticVariation
|
BEFREE |
Here we have tested ten major inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia-linked mutants for ATPase activity and found that all have increased activity over the wild type, with one mutant, p97(A232E), having three times higher activity.
|
22270372 |
2012 |
|
rs781049584
|
|
Myopathy
|
|
0.010 |
GeneticVariation
|
BEFREE |
Here we have tested ten major inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia-linked mutants for ATPase activity and found that all have increased activity over the wild type, with one mutant, p97(A232E), having three times higher activity.
|
22270372 |
2012 |
|
rs781049584
|
|
Impaired glucose tolerance
|
|
0.010 |
GeneticVariation
|
BEFREE |
We therefore investigated the susceptibility of transgenic mice carrying human mutated transgenes for amyloid precursor protein (APP (SWE)) and presenilin 1 (PSEN1 (A246E)) (APP/PSEN1), or PSEN1 (A246E) alone, which are well-characterised animal models of Alzheimer's disease, to develop obesity, glucose intolerance and insulin resistance, and whether this was age- and/or diet-dependent.
|
21538175 |
2011 |
|
rs781049584
|
|
Obesity
|
|
0.010 |
GeneticVariation
|
BEFREE |
We therefore investigated the susceptibility of transgenic mice carrying human mutated transgenes for amyloid precursor protein (APP (SWE)) and presenilin 1 (PSEN1 (A246E)) (APP/PSEN1), or PSEN1 (A246E) alone, which are well-characterised animal models of Alzheimer's disease, to develop obesity, glucose intolerance and insulin resistance, and whether this was age- and/or diet-dependent.
|
21538175 |
2011 |
|
rs781049584
|
|
Amyloidosis
|
|
0.010 |
GeneticVariation
|
BEFREE |
This strain, which over-expresses both the 695 amino acid isoform of human amyloid precursor protein (APP) with K670N and M671L mutations and presenilin 1 with the A246E mutation, has accelerated amyloidosis and plaque formation.
|
20630068 |
2010 |
|
rs781049584
|
|
Neuroblastoma
|
|
0.010 |
GeneticVariation
|
BEFREE |
Experimentally, increased PP2Ac-Yp307 was observed in mouse N2a neuroblastoma cells that stably express the human amyloid precursor protein with Swedish mutation (APPswe) compared with wild-type, and in the brains of transgenic APPswe/ presenilin (PS1, A246E) mice, which corresponded to the increased tau phosphorylation.
|
18208556 |
2008 |
|
rs781049584
|
|
Childhood Neuroblastoma
|
|
0.010 |
GeneticVariation
|
BEFREE |
Experimentally, increased PP2Ac-Yp307 was observed in mouse N2a neuroblastoma cells that stably express the human amyloid precursor protein with Swedish mutation (APPswe) compared with wild-type, and in the brains of transgenic APPswe/ presenilin (PS1, A246E) mice, which corresponded to the increased tau phosphorylation.
|
18208556 |
2008 |
|
rs781049584
|
|
Central neuroblastoma
|
|
0.010 |
GeneticVariation
|
BEFREE |
Experimentally, increased PP2Ac-Yp307 was observed in mouse N2a neuroblastoma cells that stably express the human amyloid precursor protein with Swedish mutation (APPswe) compared with wild-type, and in the brains of transgenic APPswe/ presenilin (PS1, A246E) mice, which corresponded to the increased tau phosphorylation.
|
18208556 |
2008 |