Environmental Factors Preceding A 40 Monomer to Oligomers and the Detection of Oligomers in Alzheimer's Disease Patient Serum

We present here environmental factors including pH shifts, temperature, and metal ions surrounding Aβ40 monomer to precede the oligomers. We also suggest a new idea to detect Aβ40 oligomers with anti-Aβ40 monoclonal antibody using enzyme-linked immunosorbent assay. This method involves the different sensitivity of the thermal shifts between Aβ40 monomer and the oligomers. The idea is useful for the diagnostics of Alzheimer's disease to detect Aβ40 oligomers in the serum from the patients. 1. Introduction Alzheimer’s disease (AD) is the most common of senile dementia and characterized by memory loss, deterioration of cognitive and behavioral processes and social life, and these symptoms showed no relief through the life. The major pathological hallmark of AD is the accumulated Aβ plaques in the extracellular liquid [1] and neurofibrillary tangles in the intracellular accumulation of hyperphosphorylated and misfolded tau protein [2–4]. Among the brain lesions that are affected in AD and contain the highest number of senile plaques are the amygdala [5] and hippocampus [6]. The amygdala is involved in modulation of behavior, emotion, and memory due to its vast afferent and efferent projections. It has been reported that although lesions of amygdala alone do not appear to impair spatial learning, they potentiate hippocampus lesion-induced disruption of spatial learning [7]. The Aβ plaques are mainly composed of β-structured fibrils made up to β-amyloid protein 40/42 amino acid residues long (Aβ40/42), and they are processed from amyloid precursor protein (APP) in neurons and secreted into the interstitial fluid space (IFS) of the brain in the soluble form [8] and cerebrospinal fluid (CSF) that help to clear Aβ from IFS to the bloodstream [9, 10]. Some of misfolding mechanisms of Aβ to induce aggregation appear in AD brain. Because the aggregated Aβ is observed as extracellular structure, the concentration of Aβ in the ISF [15] and the environmental factors surrounding the protein may affect the process. Detection of the most toxic Aβ species to synapse and neuron [16] present during Aβ aggregation is a critical aspect in AD diagnostics. The molten-globule state of the protein that is a misfolding intermediate, Aβ oligomers before Aβ plaque formation is responsible for neuronal damages [17]. One possible model of direct Aβ cytotoxicity involves the cytopathic effect of amyloid fibrils, which are rich in β-sheets and thereby interact with cell surface receptors and result in aberrant activation of signal transduction pathways. This model in consistent with the