Somatostatin (SST) blocks the aggregation of Aβ and inflammation whereas reduction of SST levels in the CSF and brain tissue is associated with impaired cognitive function and memory loss.
The elevation of Rac1 activity not only accelerated 6-hour spatial memory decay in 3-month-old APP/PS1 mice, but also significantly contributed to severe memory loss in aged APP/PS1 mice.
More importantly, the Pt<sup>II</sup> -PW<sub>11</sub> greatly reduced Aβ deposition and rescued memory loss in APP/PS1 transgenic AD model mice without noticeable cytotoxicity, demonstrating its potential as drugs for AD treatment.
Here, we use the J20-APP AD mouse model that displays spatial memory loss as well as reduced slow gamma amplitude and phase-amplitude coupling to theta oscillations phase.
Treatment of 3xTg-AD mice with flavocoxid reduced: (1) learning and memory loss; (2) the increased eicosanoid production and the phosphorylation level of amyloid precursor protein (APP-pThr668), Aβ 1-42, p-tau (pThr181), pERK, and the activation of the NLRP3 inflammasome; (3) Aβ plaques; and (4) neuronal loss, compared to saline-treated animals.
Three months of treatment of AAV9-GFP-CIP reduced pathologic changes, including τ hyperphosphorylation, (Aβ) deposit, astrocytosis, and microgliosis, which were correlated with the reversal of memory loss and anxiety-like behavior observed in APP/PS1 mice.
A CNS-permeable Hsp90 inhibitor rescues synaptic dysfunction and memory loss in APP-overexpressing Alzheimer's mouse model via an HSF1-mediated mechanism.
APP/PS1 double-transgenic mice treated with 3F5 mAb showed reduced memory loss, cognitive decline, and decreased levels of amyloid deposits in the brain.
Presenilin 1 transgene addition to amyloid precursor protein overexpressing transgenic rats increases amyloid beta 42 levels and results in loss of memory retention.
The amyloid precursor protein (APP) and its cleavage product Aβ play central roles in synapse and memory loss, and thus are strongly implicated in the pathogenesis of AD.
The brain formaldehyde level in APP/PS1-transgenic (n=8) mice at age of 3 months and APP-transgenic (n=8) mice at age of 6 months was increased (0.56 ± 0.02 mM), respectively, as compared with their respective age-matched controls, when these two types of AD-like animals, respectively, started to form Aβ deposits and memory loss obviously.
Transgene expression of familial Alzheimer's disease-linked mutants of β-amyloid precursor protein (APP) and presenilin-1 leads to a significant inhibition of neurogenesis, which is potentially linked to age-dependent memory loss.
Functionally, removing CX3CR1 in human amyloid precursor protein mice worsened the memory retention in passive avoidance and novel object recognition tests, and their memory loss in the novel object recognition test is associated with high levels of interleukin 6.
An increased amount or mutation(s) in PS1, which alters the stoichiometric balance of the gamma-secretase complex, may be the cause of aberrant or increased processing of APP, resulting in Abeta accumulation leading to loss of memory.
The amyloid hypothesis does not adequately address the pathogenesis of the disease, however, since transgenic mice that express the pathologic mutations of the APP and presenilin-1 (PS1) genes produce amyloid plaques but fail to exhibit neurodegeneration and memory loss observed in AD patients.
This suggests that the memory loss in APP+PS1 transgenic mice may model the early memory dysfunction in AD before the degeneration of synapses and neurons.
(2) To test whether dimemorfan has anti-amnesic effects similar to a sigma(1) receptor agonist, this study examined its effects on scopolamine- and beta-amyloid peptide-(25-35)-induced amnesia in mice.(3) Dimemorfan (10-40 mg kg(-1), i.p.) administered 30 min before the training trial, immediately after the training trial, or 30 min before the retention test significantly improved scopolamine (1 mg kg(-1), i.p.)- or beta-amyloid peptide-(25-35) (3 nmol mouse(-1), i.c.v.)-induced amnesia in a step-through passive avoidance test.Dimemorfan (5-40 mg kg(-1), i.p.) pretreatment also attenuated scopolamine (8 mg kg(-1), i.p.)-induced amnesia in a water-maze test.
A significant component of memory loss in APP transgenic mice is apparently caused by soluble A Beta assemblies, but whether and how much of the dementia within individuals afflicted with AD is caused by these A Beta species is unclear.
Transgenic mice which carried the mutant form of the beta-amyloid precursor protein gene expressed high concentrations of mutant copy of the gene and exhibited abundant amyloid plaques in the brain and memory loss.
Somatostatin (SST) blocks the aggregation of Aβ and inflammation whereas reduction of SST levels in the CSF and brain tissue is associated with impaired cognitive function and memory loss.