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.
Tetrahydroxystilbene glucoside antagonizes age-related α-synuclein overexpression in the hippocampus of APP transgenic mouse model of Alzheimer's disease.
It impedes survival factors and enhances amyloid precursor protein expression thus suggesting its involvement in the Abeta-mediated pro-apoptotic pathways in AD.
The amyloid-β (Aβ) peptide has been identified as a possible link between AD and seizures, and while Aβ is known to affect neuronal activity, the full-length amyloid precursor protein (APP) and other APP cleavage products may be important for the development and maintenance of cortical network hyperexcitability.
We previously reported that PGC-1α also regulates the transcription of β-APP cleaving enzyme (BACE1), the main enzyme involved in Aβ generation, and its expression is decreased in AD patients.
Moreover, WGA-grafted CRM-CL/LIP and WGA-grafted NGF-CL/LIP significantly improved the permeation of CRM and NGF across the blood-brain barrier, reduced Aβ plaque deposition and the malondialdehyde level, and increased the percentage of normal neurons and cholinergic activity in the hippocampus of AD rats.
Patients with trisomy 21 [Down syndrome (DS)] progressively develop amyloid beta-protein (A beta) deposits and then other features of Alzheimer's disease (AD), apparently due to increased gene dosage and thus expression of the beta-amyloid precursor protein.
The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics-relevance for Alzheimer's disease.
Significantly, inhibitors of cathepsin B improved memory, with reduced amyloid plaques and decreased Abeta(40/42) in brains of AD animal models expressing amyloid precursor protein containing the WT beta-secretase site.
Loss of BRI2 function in AD was supported by the decreased presence of BRI2-amyloid precursor protein complexes in the hippocampus of AD patients compared with control subjects.
These results suggest that APP gene expression is highly regulated in normal tissue, that many different cell classes in brain express the APP gene, and that neuronal expression may increase specifically in brain regions where widespread injury occurs in AD.
Contrary to the current AD model which positions BACE1 (β-secretase) as an aberrant or AD-advancing enzyme, it is proposed herein that the neuron's protective counteraction to this metal toxicity is, in fact, a justified increase in BACE1 activity and amyloid precursor protein (APP) processing to yield more secreted APP (sAPP) and β-amyloid peptide in response to metal toxicity.
Here we identify a β-amyloid precursor protein (APP)-interacting protein, designated as appoptosin, whose levels are upregulated in brain samples from Alzheimer's disease and infarct patients, and in rodent stroke models, as well as in neurons treated with β-amyloid (Aβ) and glutamate.
These results suggest that altered transcription of APP in AD is proportionately associated with Abeta peptide, may occur in the context of gliosis, and may contribute to Abeta deposition in sporadic AD.
To estimate vulnerability to Abeta senile plaque formation, we measured the relative mRNA levels of APP695, APP751, APP770, BACE, presenilin-1 (PS-1) and neprilysin in nine brain areas and in heart, liver, spleen and kidney in a series of Alzheimer disease (AD) and control cases.
In a variety of experimental in vitro and in vivo settings, FAD-linked presenilin variants influence the processing of the amyloid precursor protein (APP), leading to elevated levels of the highly fibrillogenic Abeta1-42 peptides that are preferentially deposited in the brains of Alzheimer Disease (AD) patients.
These results are of interest given the expression of APP early in nervous system development affecting neural migration and the role of amyloid processing in Alzheimer's disease, while dopamine has roles in the developing retina as well as in Parkinson's disease and schizophrenia.
Furthermore, A2M has been shown to reduce betaAP fibril formation, and it is upregulated in the acute-phase inflammatory response like the process occurring in the AD brain.
Co-expression of mutant amyloid precursor protein, accelerates alpha-synuclein aggregation and enhances the neurodegenerative pathology in these mice, providing a unique model where to investigate the interactions between Abeta1-42 and alpha-synuclein and to develop treatments for combined Alzheimer's disease and PD.
Our study provides a novel insight that APP overexpression may contribute to the growth impairment in DS patients and promote AD pathogenesis by inhibiting cell proliferation including neural stem cell proliferation and neurogenesis.
Overexpression of sorLA in neurons causes redistribution of APP to the Golgi and decreased processing to Abeta, whereas ablation of sorLA expression in knockout mice results in increased levels of Abeta in the brain similar to the situation in AD patients.
As a model for biological aging, the process of cellular senescence in vitro was used. mRNA levels of beta-amyloid precursor protein associated with Alzheimer disease were compared in human fibroblasts in culture at early passage and when the same fibroblasts were grown to senescence after more than 52 population doublings.
In addition, we compared SorCS1 expression levels of affected and unaffected brain regions in AD and control brains in microarray gene expression and real-time polymerase chain reaction (RT-PCR) sets, explored the effects of significant SORCS1-SNPs on SorCS1 brain expression levels, and explored the effect of suppression and overexpression of the common SorCS1 isoforms on APP processing and Aβ generation.
Previous studies have shown that sumoylation of amyloid precursor protein (APP) is associated with decreased levels of amyloid beta (Aβ) proteins, suggesting that sumoylation may play a role in the pathogenesis of Alzheimer's disease (AD).