In an Alzheimer's model using 5×FAD mice, intake of the WY peptide also suppressed microglial inflammation and accumulation of Aβ, which improved cognitive decline.
Here, the novel small molecule OAB-14, designed using bexarotene as the lead compound, significantly alleviated cognitive impairments in amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice after administration for 15 days or 3 months.
These results suggest that phenotypes for onset and rate of cognitive decline vary with PSEN1 and APP genes, suggesting a behavioral heterogeneity in ADAD.
Mutations in the presenilin 1 (PS1) gene are a major trigger of familial Alzheimer's disease (AD), yet the mechanisms affected by mutated PS1 causing cognitive decline are not yet elucidated.
Here, we report a 37-year-old male Korean patient carrying a PSEN1p.Gly417Ala mutation with exceptionally early and severe presentations, including a wide range of atypical symptoms of rapid cognitive decline with a stooped posture, rigidity, and bradykinesia.
Our results indicated that TFDM treatment ameliorated cognitive impairments and neurodegeneration and improved the antioxidant defense system in APP/PS1 mice.
Importantly, inhibition of PKCδ by rottlerin markedly reduces BACE1 expression, Aβ levels, and neuritic plaque formation and rescues cognitive deficits in an APP Swedish mutations K594N/M595L/presenilin-1 with an exon 9 deletion-transgenic AD mouse model.
The therapeutic effects of Simvastatin were evaluated in 24-month-old triple-transgenic Alzheimer's disease (3×Tg-AD) mice, and the efficacy of Simvastatin in attenuating memory and cognitive impairment was investigated.
Here, we confirmed that the increase of miR-34a expression in APP/PS1 mice was earlier than the relevant AD pathological characteristics, such as amyloid-β production, amyloid plaque deposition, and cognitive deficits.
Then we assessed the cognitive function of 12-month-old APP (amyloid precursor protein)/PS1 (presenilin 1)/Gfap-Cx43 KO mice, which demonstrated that the deletion of astroglial Cx43 significantly ameliorated cognitive dysfunction.
Here, we determined whether dietary D-PUFA would ameliorate Aβ pathology and/or cognitive deficits in a mouse model of AD (amyloid precursor protein/presenilin 1 double mutant transgenic mice).
The senile plaques (SPs) in the brain are one of the most pathophysiological characteristics of cognitive dysfunction and its major constituent amyloid β (Aβ) released from amyloid precursor protein (APP) by β (BACE1) and γ (presenilin 1) secretases .
Our data demonstrates that psen1 splicing interference induces phenotypes that resemble early-stage AD, including cognitive deficit, Aβ<sub>1-42</sub> accumulation and synaptic reduction, reinforcing the potential contribution of zebrafish larvae to studies of human brain diseases.
Reversal of high fat diet-induced obesity improves glucose tolerance, inflammatory response, β-amyloid accumulation and cognitive decline in the APP/PSEN1 mouse model of Alzheimer's disease.
We thus evaluated seizure susceptibility and hippocampal network hyperexcitability at ~3 weeks of age [prior to amyloid beta (Aβ) plaque deposition, neurofibrillary pathology, and cognitive impairment] in a triple transgenic mouse model of familial AD (3xTg-AD mouse) that harbors mutated human Aβ precursor protein (APP), tau and presenilin 1 (PS1) genes.
In this study, we investigated the effect of T4 on cognitive decline and synaptic plasticity in five times familial AD (5XFAD) mice co-expressing mutated amyloid precursor protein and presenilin-1.
Chronic LTG treatment rescues the suppressed long-term potentiation, loss of spines and cognitive deficits in AβPP/PS1 mice, known to overexpress a chimeric mouse/human mutant amyloid-β protein precursor (AβPP) and a mutant human presenilin 1 (PS1).
The PSEN1F177S mutation leads to typical AD starting at age 30 and a homogeneous phenotype with rapid cognitive decline and prominent neurological symptoms.
Presenilin 1 (PSEN1) gene mutations deterministic for Alzheimer's disease (AD) are associated with marked heterogeneity in clinical phenotype, with behavioral and psychiatric features, parkinsonism, myoclonus, epileptic seizures, spastic paraparesis, frontal behavioral changes suggestive of the phenotype of frontotemporal dementia, aphasia, and cerebellar ataxia being described as well as cognitive decline.
Indeed, the most popular genetic AD mouse lines bearing mutations of the amyloid precursor protein (APP) and presenilin 1 genes (PS1), often fail to present robust cognitive deficits or show them only at very advanced ages.