Reduced action of thyroid hormone on the APP gene may contribute to AD pathology by increasing APP expression and the levels of processed APP products.
Large and rare copy number variants (CNVs) are known to confer risk in several related disorders including Alzheimer's disease (at APP), schizophrenia, epilepsy, mental retardation, and autism.
Processing of the amyloid precursor protein (APP) by β- and γ-secretases generates pathogenic β-amyloid (Aβ) peptides associated with Alzheimer disease (AD), whereas cleavage of APP by α-secretases precludes Aβ formation.
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.
To address the latter, we generated APP transgenic mice expressing the E693Delta mutation, which causes AD by enhanced Abeta oligomerization without fibrillization.
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.
To study the putative precursor proteins (PreA4(695), PreA4(751), and PreA4(770] of Alzheimer's disease A4 amyloid protein, polyclonal and monoclonal antibodies were raised against a recombinant bacterial PreA4(695) fusion protein.
We now know of the existence of at least three AD loci on chromosomes 14, 19, and 21 and are beginning to understand the role that one of these loci, APP, and its mutations plays in the progression of AD.
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.
Three mutations have been reported at APP 717, just distal to the C-terminus of the beta-amyloid domain, APP 717 val-ile, APP 717 val-phe, and APP 717 val-gly, which are associated with autopsy-proven Alzheimer's disease (AD).
Amyloid precursor protein (APP) is endoproteolytically processed by BACE1 and gamma-secretase to release amyloid peptides (Abeta40 and 42) that aggregate to form senile plaques in the brains of patients with Alzheimer's disease (AD).
Iron and the translation of the amyloid precursor protein (APP) and ferritin mRNAs: riboregulation against neural oxidative damage in Alzheimer's disease.
Using a mouse model of AD (APP-PSEN1-SREBF2 mice), expressing chimeric mouse-human amyloid precursor protein with the familial Alzheimer Swedish mutation (APP695swe) and mutant presenilin 1 (PSEN1-dE9), together with a dominant-positive, truncated and active form of SREBF2/SREBP2 (sterol regulatory element binding factor 2), we demonstrated that high brain cholesterol enhanced autophagosome formation, but disrupted its fusion with endosomal-lysosomal vesicles.
These results indicate that the upregulation of dural lymphangiogenesis facilities amyloid-β clearance from the brain of APP/PS1 mice, suggesting the potential of the VEGF-C/VEGFR-3 signaling pathway as a therapeutic target for Alzheimer's disease.
Here we present studies of a pathogenic amyloid precursor protein (APP) mutation, located within the Abeta sequence at codon 693 (E693G), that causes AD in a Swedish family.
While a commonly accepted model argues that Abeta peptides are the cause of onset and early pathogenesis of Alzheimer's disease, recent discussions challenge this 'Abeta hypothesis' and suggest a direct role for APP in this neurodegenerative disease.
Transgenic APPSwe/PS1dE9 (APP/PS1) mice that overproduce amyloid beta (Aβ) are extensively used in the studies of pathogenesis and experimental therapeutics and new drug screening for Alzheimer's disease (AD).
This review highlights how APP transgenic mouse models have successfully been used in drug discovery to support the progression of A lowering therapeutics to clinical trials to ultimately test the 'amyloid hypothesis' of AD.
Our results indicate that the pathologic features of AD are exaggerated in the brain of APP transgenic mice that have concurrent insulin-deficient diabetes, and underscore a possible mechanism of brain dysfunction common to AD and diabetes.