BACKGROUND. Neuronal hyperexcitability characterizes the early stages of Alzheimer’s disease (AD). In animals, misfolded tau and amyloid-β (Aβ) protein accumulation — both central to AD neuropathology promote cortical excitability neuronal network dysfunction. healthy humans, Aβ aggregates are first detected, respectively, in brainstem frontomedial temporobasal cortices, decades prior onset cog...

The amyloid hypothesis suggests that beta-amyloid (Aβ) deposition leads to alterations in neural function and ultimately to cognitive decline in Alzheimer's disease. However, factors that underlie Aβ deposition are incompletely understood. One proposed model suggests that synaptic activity leads to increased Aβ deposition. More specifically, hyperactivity in the hippocampus may be detrimental a...

Abstract Objective We assessed the performance of plasma amyloid oligomerization tendency (OAβ) as a marker for abnormal status. Additionally, we examined long-term storage effects on OAβ. Methods included 399 subjects regardless clinical diagnosis from Amsterdam Dementia Cohort and European Medical Information Framework AD project (age, 63.8 ± 6.6; 44% female). Amyloid status was determined by...

Activated monoamine oxidase (MAO) has a critical role in the pathogenesis of Alzheimer's disease (AD), including the formation of amyloid plaques from amyloid β peptide (Aβ) production and accumulation, formation of neurofibrillary tangles, and cognitive impairment via the destruction of cholinergic neurons and disorder of the cholinergic system. Several studies have indicated that MAO inhibito...

Amyloid β peptide (Aβ) is the major pathogenic molecule in Alzheimer's disease (AD). BACE1 enzyme essential for generation of Aβ. Deficiency p38α-MAPK neurons increases lysosomal degradation and decreases Aβ deposition brain APP-transgenic mice. However, mechanisms mediating effects are largely unknown. In this study, we used mice cultured observed that deletion specifically decreased phosphory...

Extracellular β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) are the pathological hallmarks of Alzheimer’s disease (AD). Studies have shown that aggregates extracellular Aβ can induce neuroinflammation mediated neurotoxic signaling through microglial activation release pro-inflammatory factors. Thus, modulation might be a potential therapeutic strategy for modifying progression. Rece...

Recent epidemiology studies have indicated that traumatic brain injury (TBI) can increase the risk of developing neurodegenerative diseases such as Alzheimer's disease (AD). Amyloid-β (Aβ) plaques and neurofibrillary tangles are pathological indicators of AD. The accumulation of Aβ is considered the first step of AD pathophysiology. Compelling studies have supported the hypothesis that TBI acce...

Alzheimer's disease is characterized by neuronal loss and cerebral accumulation of amyloid-β protein (Aβ) and lowering the generation of Aβ is a pivotal approach in the strategy of Alzheimer's disease treatment. Midlife hypertension is a major risk factor for the future onset of sporadic Alzheimer's disease and the use of some antihypertensive drugs may decrease the incidence of Alzheimer's dis...

Tissue-specific overexpression of the human systemic amyloid precursor transthyretin (TTR) ameliorates Alzheimer's disease (AD) phenotypes in APP23 mice. TTR-β-amyloid (Aβ) complexes have been isolated from APP23 and some human AD brains. We now show that substoichiometric concentrations of TTR tetramers suppress Aβ aggregation in vitro via an interaction between the thyroxine binding pocket of...

Extracellular accumulation of amyloid-beta (Aβ) plaques is one the major pathological hallmarks Alzheimer's disease (AD), and target only FDA-approved disease-modifying treatment for AD. Accordingly, use transgenic mouse models that overexpress amyloid precursor protein thereby accumulate cerebral Aβ are widely used to model human AD in mice. Therefore, immunoassays, including enzyme-linked imm...