The details of trafficking and processing of APP to Aβ, the cytosolic intracellular Aβ domain (AICD) and small soluble proteins are shown, together with other amyloid-forming proteins such as tau and α-synuclein (α-syn).
APP/PS1 mice also exhibited higher amyloid-β40 and amyloid-β42 in their cortex, accumulation of mitochondria APP in their cortex, and presented an altered oxidative state in their brain.
In Alzheimer's disease, BACE1 protease initiates the amyloidogenic processing of amyloid precursor protein (APP) that eventually results in synthesis of β-amyloid (Aβ) peptide.
The experimental results showed that VAC at sub-micromolar concentrations improved the viability of neural cells with or without increased β-amyloid (Aβ) burden; and in APP/PS1 transgenic mice, VAC treatment (0.1 mmol kg<sup>-1</sup> d<sup>-1</sup>) preserved cognitive function and attenuated neuron loss, but did not reduce brain Aβ plaques.
To better study the consequences of reducing BACE metabolism, specifically of APP, we used an antibody, 2B3, that binds to APP at the BACE cleavage site, inhibiting Aβ production.
By contrast, in younger age groups, APP expression is not associated with amyloidosis, instead it acts solely as a neuroprotectant while facilitating cellular ferroportin-dependent iron efflux.
Changes in amyloid precursor protein (APP) cleavage and production of the APP fragment beta-amyloid (Aβ) along with hyperphosphorylated tau protein aggregation coalesce to cause reduction in synaptic strength, synaptic loss, and neurodegeneration.
Here, we show that absence of TYROBP/DAP12 in a mouse model of AD-type cerebral Aβ amyloidosis (APP<sup>KM670/671NL</sup>/PSEN1<sup>Δexon9</sup>) recapitulates the expected network characteristics by normalizing the transcriptome of APP/PSEN1 mice and repressing the induction of genes involved in the switch from homeostatic microglia to disease-associated microglia (DAM), including Trem2, complement (C1qa, C1qb, C1qc, and Itgax), Clec7a and Cst7.
The effect of justicidin A on Aβ production was blocked by endocytosis inhibitors, indicating that the decreased APP endocytosis by justicidin A is the underlying mechanism.
APP plays a greater role in AD pathogenesis than its role as the precursor for Aβ peptides: both the abnormal cleavage of APP leading to Aβ peptide accumulation and the disruption of APP physiological functions contribute to AD pathogenesis.
In human glioblastoma A172 cells and neuroblastoma SH-SY5Y cells, we delineated the Dl-NBP-mediated signaling pathways by which Dl-NBP-dependent upregulation of Nrf2 mediated the reciprocal regulation of reducing proinflammatory cytokine and inhibiting Aβ production in the glial and neuronal cells overexpressing APPswe.
In this study, we have examined the effect of TBI on subsequent beta-amyloid (Aβ) deposition in APP/PS1 (APP<sub>SWE</sub>/PSEN1dE9) transgenic mice either before (3 months of age) or after the onset (6 months of age) of plaque pathology.
Amyloid precursor protein (APP) is processed along the amyloidogenic pathway by the β-secretase, BACE1, generating β-amyloid (Aβ), or along the nonamyloidogenic pathway by α-secretase, precluding Aβ production.
The TgF344-AD rat model of AD, bearing mutant human amyloid precursor protein (APPswe) and Presenilin 1 (PSEN1ΔE9) genes, has been described to manifest the full spectrum of AD pathology similar to human AD, i.e. progressive cerebral amyloidosis, tauopathy, neuronal loss and age-dependent cognitive decline.
We examined the occurrence of behavioral, cognitive and neuroimaging changes in APP<sup>NL-G-F</sup> knock-in mice that display Aβ42 amyloidosis in the absence of APP overexpression.
We found that EPPS treatment profoundly reduced the accumulation of beta-amyloid precursor protein (β-APP) and Aβ over a widespread area detected in the pericontusional cortex, external capsule (EC), and hippocampal CA1 and CA3 at 3 days after TBI, accompanied by significant reduction in the TBI-induced diffuse axonal injury identified by increased immunoreactivity of SMI-32 (an indicator for axonal damage).
We demonstrated that an antibiotic cocktail (ABX)-perturbed gut microbiome is associated with reduced amyloid-β (Aβ) plaque pathology and astrogliosis in the male amyloid precursor protein (<i>APP)<sub>SWE</sub></i> /presenilin 1 <i>(PS1)<sub>ΔE9</sub></i> transgenic model of Aβ amyloidosis.
Chronic stress is a major risk factor for developing Alzheimer's disease (AD) and promotes the processing of amyloid precursor protein (APP) to β-amyloid (Aβ).