Our results thus for identified the role of GBF1 in APP trafficking and cleavage, and provide evidence for GBF1 as a possible therapeutic target in AD.
<b>Methods</b>: The AD animal model (APP/PS1 transgenic mice) and KIBRA knockout (KIBRA KO) mice were used to investigate pathophysiological changes of KIBRA <i>in vivo</i>.
Cleavage of the amyloid precursor protein's (APP) transmembrane domain (TMD) by γ-secretase is a crucial step in the aetiology of Alzheimer's Disease (AD).
Interestingly, reduced nuclear mSREBP-2 was only found in animal models of tauopathies such as 3XTg AD mice and P301L Tau Tg mice but not in CRND8 APP transgenic mice, suggesting that tau alterations likely are involved in the changes of mSREBP-2 distribution and activation in AD.
Among the most commonly used models are transgenic mice overexpressing human amyloid precursor protein (APP) with mutations linked to familial AD, resulting in the formation of amyloid β plaques, one of the pathological hallmarks observed in AD patients.
It is not known whether the coaggregation of tau and α-synuclein in dominantly inherited AD occurs in association with specific mutations of the APP, PSEN1, or PSEN2 genes.
We studied a range of retinal functional and structural parameters in association with AD- specific pathophysiological markers in the double transgenic APP/PS1 and control mice across age.
In addition, AD transgenics had an increased expression of tau, phosphorylated-tau and amyloid precursor protein in the hippocampus. tDCS did not improve behavioural deficits or mitigated the development of AD neuropathology in 3xTg animals.
The detection of elevated levels of Fe65 in the brains of both human patients and APP transgenic mice may further strengthen the hypothesis that influencing the interaction between Fe65 and APP may have a beneficial effect on the course of AD.
The absence of DAPK1 promotes efficient learning and better memory in mice and prevents the development of AD by acting on many key proteins including Pin1 and its downstream targets tau and APP.
This study was aimed to estimate variations of measures of cardiovascular risk in Alzheimer's dementia by pharmacogenetic analyses of the effects of angiotensin-converting enzyme (ACE) inhibitors and statins.
In our previous study, we discovered that a small noncoding RNA (miR-188-3p) targeting β-site amyloid precursor protein cleaving enzyme (BACE)-1, a key enzyme responsible for Aβ formation, plays an important role in the development of neuropathology in AD.
As meprin β cleavage of APP has been shown to result in formation of highly aggregation-prone, truncated Aβ2-40/42 peptides, enhanced APP processing by this enzyme could contribute to AD pathology.
The amyloid precursor protein (APP) is a type I transmembrane glycoprotein widely studied for its role as the source of β-amyloid peptide, accumulation of which is causal in at least some cases of Alzheimer's disease (AD).
Among others, such stimulation enhances APP synthesis and synapse formation with an ApoE4>ApoE3>ApoE2 potency rank order, paralleling the relative risk for AD conferred by these ApoE variants.
<b>Materials and methods:</b> Sixty APP/PS1 transgenic mice were randomly divided into an AD model group, a T10-treated group and a T4-treated group (<i>n</i> = 20); 20 wild-type littermates served as the control group.
Furthermore, intracranial injection of adeno-associated virus expressing miR-124-3p into APP/PS1-AD mice significantly reduced Aβ deposition and significantly improved the AD-mouse behavior in the social recognition test and plus-maze discriminative avoidance task.
Due to having three copies of the amyloid precursor protein (APP) gene which results in amyloid-beta plaque deposition, the cognitive decline often resembles the decline observed in Alzheimer's disease.
Three months later, LV-KL significantly induced Klotho overexpression in the brain and effectively ameliorated cognitive deficit and AD-like pathology in amyloid precursor protein/presenilin 1 mice.
Reverting Metabolic Dysfunction in Cortex and Cerebellum of APP/PS1 Mice, a Model for Alzheimer's Disease by Pioglitazone, a Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Agonist.
During the last three decades, results from several independent studies have converged to form the so-called amyloid cascade hypothesis of AD and several therapeutic strategies designed to modulate the APP amyloidogenic pathway have been developed.