One important pathologic feature of AD is the formation of extracellular senile plaques in the brain, whose major components are small peptides called beta-amyloid (Abeta) that are derived from beta-amyloid precursor protein (APP) through sequential cleavages by beta-secretase and gamma-secretase.
The generation of Aβ, the main component of senile plaques in Alzheimer's disease (AD), is precluded by α-secretase cleavage within the Aβ domain of the amyloid precursor protein (APP).
To identify epigenetically regulated genes involved in the pathogenesis of Alzheimer's disease (AD) we analyzed global mRNA expression and methylation profiles in amyloid precursor protein (APP)-Swedish mutant-expressing AD model cells, H4-sw and selected heme oxygenase-1 (HMOX1), which is associated with pathological features of AD such as neurofibrillary tangles and senile plaques.
In addition, administration of TBTC (30mg/kg/day) in the transgenic APP-PS1 mice could also reduce the formation of senile plaques and improve the daily living activity of the mice.
Alzheimer's disease (AD) is a degenerative disorder typified by progressive deterioration of memory and the appearance of β-amyloid peptide (Aβ)-rich senile plaques.
Amyloid-beta (Abeta) the primary component of the senile plaques found in Alzheimer's disease (AD) is generated by the rate-limiting cleavage of amyloid precursor protein (APP) by beta-secretase followed by gamma-secretase cleavage.
Histopathological hallmarks are represented by aggregates of beta-amyloid peptide (Aβ) in senile plaques and deposition of hyperphosphorylated tau protein in neurofibrillary tangles in the brain.
The characteristic hallmarks of the disease are extracellular senile plaques (SPs) and intracellular neurofibrillary tangles (NFTs) with neuropil threads, which are a direct result of amyloid precursor protein (APP) processing to Aβ, and τ hyperphosphorylation.
Transgenic (Tg) mouse models overexpressing amyloid precursor protein (APP) develop senile plaques similar to those found in Alzheimer's disease in an age-dependent manner.
beta-amyloid peptide (A beta) and complement-derived membrane attack complex (MAC) are co-localized in senile plaques of brains from Alzheimer's disease (AD) patients.
Our experiments clearly show that trans fatty acids compared to cis fatty acids increase amyloidogenic and decrease nonamyloidogenic processing of APP, resulting in an increased production of amyloid beta (Aβ) peptides, main components of senile plaques, which are a characteristic neuropathological hallmark for Alzheimer's disease (AD).
In addition, the level of soluble Aβ1-42 has been shown to correlate with cognitive impairment in animal models before the presence of senile plaques or other histological features of AD.
Downregulation of lncRNA BACE1‑AS expression in SH‑SY5Y cells by siRNA silencing resulted in the attenuation of the ability of BACE1 to cleave APP and delayed the induction of SP formation in the SP AD SH‑SY5Y cell model.
Fibrillar beta-amyloid peptide, a major component of senile plaques in AD brain, is known to induce microglial-mediated neurotoxicity under certain conditions, but some recent studies support the notion that Abeta oligomers are the primary neurotoxins.
Amyloid precursor protein (APP) proteolysis is essential for the production of β-amyloid peptides (Aβ) that form senile plaques in Alzheimer's disease (AD) brains.
The neuropathology of Alzheimer's disease (AD) is characterized by the widespread accumulation of neuritic plaques and neurofibrillary tangles composed of deposits of beta-amyloid peptide (Aβ) and abnormally phosphorylated tau protein (phospho-tau) respectively.
The main constituent of senile plaques is amyloid beta-peptide (A beta) and in recent years, pathogenic mutations in the amyloid precursor protein (APP) gene have been discovered in some AD families.
In this study, we evaluated the effects of enriched environment (EE) stimulation on spatial memory and senile plaque formation in transgenic mice PDGFB-APPSwInd (TG) that overexpress the human amyloid precursor protein, normally resulting in an increased density of senile plaques.
We found that oral treatment with FLDK reversed learning and memory impairment, reduced Aβ burden and expression of β-site amyloid precursor protein cleavage enzyme 1 (BACE1), and decreased microglial activation in senile plaques.
We found that Zn<sup>2+</sup> induces APP-C99 dimerization, which prevents its cleavage by γ-secretase and Aβ production, with an IC<sub>50</sub> value of 15 μm Importantly, at this concentration, Zn<sup>2+</sup> also drastically raised the production of the aggregation-prone Aβ43 found in the senile plaques of AD brains and elevated the Aβ43:Aβ40 ratio, a promising biomarker for neurotoxicity and AD.
A novel magnetic resonance (MR) imaging contrast agent based on a derivative of human amyloid beta (Abeta) peptide, Gd[N-4ab/Q-4ab]Abeta 30, was previously shown to cross the blood-brain barrier (BBB) and bind to amyloid plaques in Alzheimer's disease (AD) transgenic mouse (APP/PS1) brain.