This set of genes are implicated in important biological processes and molecular functions commonly affected by genes associated with the etiology of AD such as APP, APOE, and CLU.
Because Gal-3 expression is dramatically increased as early as 3 months of age in APP/PS1 mice and anti-Aβ oligomerization is believed to protect against Aβ toxicity, Gal-3 could be considered a novel therapeutic target in efforts to combat AD.
Here, we investigated the roles of NDRG2 in the development of memory impairment in AD using mouse models established by amyloid β injection or crossing of APP/PS1 mice.
One of the important therapeutic approaches of AD is the inhibition of β-site APP cleaving enzyme-1 (BACE1), which is involved in the rate-limiting step of the cleavage process of the amyloid precursor protein (APP) leading to the generation of the neurotoxic amyloid β (Aβ) protein after the γ-secretase completes its function.
Down syndrome (DS) patients are more susceptible to Alzheimer's disease (AD) due to the presence of three copies of genes on chromosome 21 such as DYRK1A, which encodes a broad acting kinase, and APP (amyloid precursor protein), leading to formation of amyloid beta (Aβ) peptide and hyperphosphorylation of Tau.
Here, we applied multilayered N-glycoproteomics to quantify the global protein expres-sion levels, N-glycosylation sites, N-glycans, and site-specific N-glycopeptides in AD (APP/PS1 transgenic) and wild-type mouse brains.
Activated AEP cleaves both APP and Tau at APP N585 and Tau N368 sites, respectively, which mediate AD pathogenesis by promoting Aβ production and Tau hyperphosphorylation and inducing neuroinflammation and neurotoxicity.
We applied the approach to the exploration of ligands for β-site amyloid precursor protein [APP]-cleaving enzyme 1 (BACE1), a major target for Alzheimer Disease (AD), with less off-target effect toward cathepsin D. We demonstrated that the density region of BACE1 and cathepsin D ligands are well-divided, and a group of natural compounds as a target for exploration of new drug candidates also has significantly different distribution on the density map.
We next cross-bred the <i>MAPT</i> knock-in mice with single amyloid precursor protein (<i>App</i>) knock-in mice to investigate the Aβ-tau axis in AD etiology.
The proband carried an APP missense variant in homozygous state (NM_000484.4: c.2032G>A; NP_000475.1: rs63750064" genes_norm="351">p.Asp678Asn; rs63750064) and showed a more severe clinical picture than the other AD relatives, as regards the age of onset and the rate of disease progression.
In this Review, we summarize research progress on the modification of glycosylation, especially O-GlcNAcylation and mucin-type O-linked glycosylation (also known as O-GalNAcylation), on the regulation of AβPP cleavage and on the influence of AβPP's glycosylation in the pathogenesis of AD.
Therefore, the purpose of this study was to investigate the effect of progesterone on the glucose metabolism of neurons in amyloid precursor protein (APP)/presenilin 1 (PS1) mice and Aβ-induced AD cell model.
As a result, the nanochaperone reduces Aβ burden, attenuates Aβ-induced inflammation, and eventually rescues the cognitive deficits of APP/PS1 transgenic AD mice.
Mutations in PSEN and the Amyloid Precursor Protein (APP) cause early-onset AD GSECs successively cut APP to generate amyloid-β (Aβ) peptides of various lengths.
Amyloid precursor protein (APP) is implicated in neural development as well as in the pathology of Alzheimer's disease (AD); however, its biological function still remains unclear.
The membrane protease γ-secretase cleaves the C99 fragment of the amyloid precursor protein, thus producing the Aβ peptides central to Alzheimer's disease.
Dermal fibroblasts were obtained from a 55 year old male Сaucasian familial Alzheimer's disease (AD) patient carrying heterozygous V717I mutation in the APP gene.
Abnormal processing of amyloid precursor protein (APP) and aggregation of the Aβ peptide are known to play a key role in the pathogenesis of Alzheimer disease, but the function of endogenous APP under normal physiological conditions remains poorly understood.
Here, using a mouse model of ADamyloid precursor protein (APP/PS1/Nestin-GFP triple transgenic mice, 3xTgAD), we examined the effects of 4 weeks of valproic acid (VPA) treatment on hippocampal neurogenesis in 2- and 6-month-old mice.
This review discusses recent advances in unravelling the membrane trafficking events associated with the production of Aβ, and how AD susceptible alleles may perturb the sorting and transport of APP and BACE1.
Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD.