Furthermore, these plant metabolites improved the lysosomal autophagy process by increasing the expression levels of Beclin-1, LC3II and cathepsin B genes for clearance of Aβ and NFT, and increased the expression of transporter proteins, P-glycoprotein (P-gp) and low density lipoprotein receptor-related protein-1 (LRP-1) for the clearance of Aβ load from brain across the blood-brain barrier (BBB) as well as increased the expression of PPAR-γ and ApoE proteins for clearance of Aβ in ApoE mediated pathway from brain.
Lower levels of percent area in APOE ε2 carriers may reflect lower total β-amyloid and may contribute to APOE ε2 carriers' decreased risk of dementia, despite high β-amyloid plaque scores.
AD-like phenotypes were altered by co-expression of PS1, including a shift from hippocampal to cortical Aβ pathology, alongside reduced deficits in spatial learning.
Using Chinese hamster ovary (CHO) APP751SW cells, we identified and characterized effects of 2-([pyridine-2-ylmethyl]-amino)-phenol (2-PMAP) on APP steady-state level and Aβ production.
The result showed that berberine significantly improved 3×Tg-AD mice's spatial learning capacity and memory retention, promoted autophagy activity identified by the enhancement of brain LC3-II, beclin-1, hVps34, and Cathepsin-D levels as well as the reduction of brain P62 and Bcl-2 levels in AD mice, facilitated reduction of Aβ and APP levels, reduced Aβ plaque deposition in the hippocampus of AD mice, and inhibited b-site APP cleavage enzyme 1 (BACE1) expression.
The relative amount of amyloid-containing fragments increased dramatically during expression of the clinical mutants, while it decreased strongly when the mouse form of APP was expressed.
Many years before AD symptoms appear, such neuroimaging procedures can disclose signature abnormalities of brain structure, function, and amyloid levels in cognitively normal apoE ε4 allele carriers and/or individuals with a family history of spAD.
The Swedish familial AD variant of APP (APP<sub>Swe</sub>) more readily co-activates non-canonical, at the expense of canonical Wnt activity, indicating that its pathogenicity likely involves direct effects on synapses, in addition to increased Aβ production.
Here, we report that the natural product arctigenin from Arctium lappa (L.) can both inhibit Aβ production by suppressing β-site amyloid precursor protein cleavage enzyme 1 expression and promote Aβ clearance by enhancing autophagy through AKT/mTOR signaling inhibition and AMPK/Raptor pathway activation as investigated in cells and APP/PS1 transgenic AD model mice.
Overexpression of amyloid precursor protein A4 (beta-amyloid) immunoreactivity in genetically transformed cells: implications for a cellular model of Alzheimer amyloidosis.
Clathrin and clathrin adaptor proteins are involved in the endocytosis of the APP protein that can lead to increased intracellular levels of amyloid beta peptide, contributing to the progression of Alzheimer's.
Transgenic overexpression of amyloid precursor protein (APP) genes that are either entirely human in sequence or have humanized Aβ sequences can produce Alzheimer-type amyloidosis in mice, provided the transgenes also encode mutations linked to familial Alzheimer's Disease (FAD).
This age-dependent shift in Aβ peptide profile coincided with reduced expression of glycosylated species of ADAM-10 (α-secretase) and BACE1 (β-secretase), and an increased co-immunoprecipitation of presenilin-1 with nicastrin (components of the γ-secretase complex).
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.
Although BIN1 is known to have a role in endocytosis, and the processing of the amyloid precursor protein (APP) to form amyloid-β (Aβ) peptides is dependent on endocytosis, knockdown of BIN1 by targeted siRNA or the overexpression of BIN1 in a human neuroblastoma cell line (SH-SY5Y) had no effect on APP processing.
We observed an increase in ADAM10 and a decrease in BACE1 and APP695 protein levels and, subsequently, a reduction in Aβ levels and Aβ burden were present in HupA-treated mouse brain, suggesting that HupA enhances the nonamyloidogenic APP cleavage pathway.
One model-dependent factor has so far been almost completely neglected: the endogenous expression of mouse APP and its effects on the transgenic models and the readout for therapeutic approaches.Here, we report that hAPP-transgenic models of amyloidosis devoid of endogenous mouse APP expression (mAPP-knockout / mAPPko) show increased amounts and higher speed of Aβ deposition than controls with mAPP.
Previously, it was shown that high Hcy increases brain β-amyloid (Aβ) levels in amyloid precursor protein transgenic mice, but no data are available on the effect that it may have on the other main pathologic features of AD such as tau.