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.
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.
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.
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.
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.
Atorvastatin prevents hippocampal cell death, neuroinflammation and oxidative stress following amyloid-β(1-40) administration in mice: evidence for dissociation between cognitive deficits and neuronal damage.
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.
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.
Protective effects of astragalosides on dexamethasone and Aβ25-35 induced learning and memory impairments due to decrease amyloid precursor protein expression in 12-month male rats.
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.
Inhibition of human high-affinity copper importer Ctr1 orthologous in the nervous system of Drosophila ameliorates Aβ42-induced Alzheimer's disease-like symptoms.
Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in an Amyloid-β Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3-Kinase (PI3K)/Akt/Wnt/β-Catenin Pathway.
Presenilin 1 transgene addition to amyloid precursor protein overexpressing transgenic rats increases amyloid beta 42 levels and results in loss of memory retention.
A CNS-permeable Hsp90 inhibitor rescues synaptic dysfunction and memory loss in APP-overexpressing Alzheimer's mouse model via an HSF1-mediated mechanism.