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The common approach of the diagnosis of Alzheimer's Disease (AD) is made with an analysis of the cerebrospinal fluid or the study of retinal fundus and the plaques formation through optical corneal tomography (OCT), or more simply with a fundus camera. Tears analysis is widely discussed in literature as an essential method to describe molecular and biochemical alterations in different diseases. The aim of our study was the identification with immunocytochemistry of Amyloid Beta-42 in tears from patients with or without familiarity for Alzheimer Disease, in order to make the diagnosis earlier and more accessible compared to other invasive methods. Our study was performed on tears from three phenotypically healthy subjects: two of them were Caucasian with Alzheimer familiarity (48 and 55 years old) and the other one was Asian without Alzheimer familiarity (45 years old) and affected by an adenoviral keratoconjunctivitis at the moment of withdrawal. Tear samples were collected from eye fornix and were examinated by immunocytochemistry (ICC) assay using anti-Amyloid Beta X-42 antibody. Two out of three tears samples showed positive Amyloid Beta-42. Considering that our patients were phenotypically healthy, the identification of Amyloid Beta-42 by ICC could be a candidable method to make the diagnosis of the disease earlier and more accessible and available then other current and invasive methods and it could be a candidate for a screening method too. [ABSTRACT FROM AUTHOR]

This study represents the development of a biosensor which is based on the liquid crystal (LC) orientation as a function of the peptide concentration to detect an amyloid-beta-42 (Aβ42) antibody–antigen binding events. The Aβ42 peptide binds to the Aβ42 antibody forming an immunocomplex which is immobilized on the Dimethyloctadecyl[3-(trimethoxysilyl)propyl] ammonium chloride (DMOAP) coated surface. The disturbed orientation of LCs as a result of the binding of the formed immunocomplex was observed using the polarized optical microscope (POM) as a function of decreasing Aβ42 peptide concentration from 1000 to 1 pg/ml. The concentration, as low as 1 pg/ml of Aβ42 peptide was able to be successfully detected in our system. Apolipoprotein E4 (ApoE4), that specifically bound to the Aβ42 peptide, was added into the system and a remarkable change in reflection spectra of samples was observed with increasing Aβ42 peptide concentration. The concentration of ApoE4 protein was detected in the range of 0.1–30 nM by this system due to the interaction between the two proteins. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Age-related macular degeneration (AMD) is a type of macular degeneration disease, and amyloid beta (aβ) is the main component of vitreous warts in AMD patients. Neovascular AMD (nAMD) is the most serious type of AMD, but its pathogenesis remains unclear. The aim of this study was to detect the expression of aβ42 in the aqueous humor of nAMD patients and to evaluate whether aβ42 expression of aqueous humor is correlated with cognitive function in these patients. Methods: A total of 70 patients were enrolled in this study, including 50 nAMD patients (nAMD group) and 20 patients with cataract (control group). The cognitive function of the patients was assessed using the Mini-Mental State Examination and Montreal Cognitive Assessment Scale, and based on their scores, 50 patients with nAMD were divided into two subgroups: the p-nAMD group (18 nAMD patients with normal cognition) and the ci-nAMD group (32 nAMD patients with cognitive impairment). An immunofluorescence microsphere probe technique was used to detect the aβ42 expression of aqueous humor in all patients. Pearson correlation analysis was used. Results: The aβ42 expression of aqueous humor was significantly higher in the nAMD group (124.56 ± 41.93 pg/mL) as compared with the control group (82.94 ± 33.75 pg/mL; P <.01). There was no significant difference in aβ42 expression of aqueous humor between the p-nAMD group (136.42 ± 51.68 pg/mL) and ci-nAMD group (117.90 ± 34.46 pg/mL; P =.14). Conclusion: In nAMD patients, aβ42 was highly expressed in the aqueous humor but was not correlated with cognitive function. [ABSTRACT FROM AUTHOR]

The common approach of the diagnosis of Alzheimer’s Disease (AD) is made with an analysis of the cerebrospinal fluid or the study of retinal fundus and the plaques formation through optical corneal tomography (OCT), or more simply with a fundus camera. Tears analysis is widely discussed in literature as an essential method to describe molecular and biochemical alterations in different diseases. The aim of our study was the identification with immunocytochemistry of Amyloid Beta-42 in tears from patients with or without familiarity for Alzheimer Disease, in order to make the diagnosis earlier and more accessible compared to other invasive methods. Our study was performed on tears from three phenotypically healthy subjects: two of them were Caucasian with Alzheimer familiarity (48 and 55 years old) and the other one was Asian without Alzheimer familiarity (45 years old) and affected by an adenoviral keratoconjunctivitis at the moment of withdrawal. Tear samples were collected from eye fornix and were examinated by immunocytochemistry (ICC) assay using anti-Amyloid Beta X-42 antibody. Two out of three tears samples showed positive Amyloid Beta-42. Considering that our patients were phenotypically healthy, the identification of Amyloid Beta-42 by ICC could be a candidable method to make the diagnosis of the disease earlier and more accessible and available then other current and invasive methods and it could be a candidate for a screening method too.

Alzheimer’s disease (AD) pathogenesis leads to the appearance of senile plaques due to the production and deposition of the β-amyloid peptide (Aβ). Superparamagnetic iron oxide nanoparticles (SPIONs) have potential role in the detection and imaging of Aβ plaques in AD. SPIONs have shown appropriate potential in the diagnosis and treatment of AD. In the present study, the pharmacokinetics of SPIONs and its effect in the biochemical pathway of AD were analyzed using collected information. During analysis, the interaction of SPIONs with amyloid beta-42 (Aβ42), a biomarker for AD progression, has been shown. Nodes represent the entities and edges represent the relation (interactions) of one node to another node. Aβ42 and their interaction with other entities making up biochemical network are involved in AD mechanism in presence of SPION. The kinetic simulation was done to investigate pharmacokinetics of SPIONs for AD, where concentration was assigned of nanoparticles and other entities were applied as a kinetic irreversible simple Michaelis-Menten or mass action kinetics. Simulation was done in presence and absence of SPIONs to investigate pharmacokinetic effect in AD and explore the mechanism of Aβ42 in presence of SPIONs. This study may lead to better understanding, which is required to target the metabolism of Aß42 peptide, a pivotal player in this pathology. [ABSTRACT FROM AUTHOR]

Amyloid beta (Aβ) is a peptide responsible for the development of Alzheimer's disease (AD). Misfolding and accumulation of endogenous Aβ can lead to neural cell apoptosis through endoplasmic reticulum (ER) stress. Added exogenous Aβ can also result in ER stress, leading to neurotoxicity and apoptosis, which is identical to that caused by the endogenous peptide. We have speculated that the endocytic transport of Aβ causes ER stress and have previously shown that the oxysterol, in particular, 7-ketocholesterol (7-keto) induces more surface interaction between Aβ-42 and Jurkat cells than cholesterol. However, the interaction was not enough to induce intracellular transfer of the peptide. In this study, we investigated the effect of another oxysterol, 25-hydroxycholesterol (25-OH) on the membrane raft-dependent transport of Aβ-42 in Jurkat cells. Interestingly, intracellular transfer of Aβ- 42 was observed in the presence of 25-OH only after the inclusion of cholera toxin B subunit (CT-B), a marker used to detect the raft domain. We speculated that 25-OH can induce intracellular movement of Aβ peptides. Furthermore, CT-B together with GM1 provided negative curvature, which resulted in the intracellular transport of Aβ-42. NotAβly, we used a protofibrillar species of Aβ-42 in this study. We have shown that the transport was microtubule- dependent since it could not be observed in depolymerized microtubules. These results demonstrate that oxysterols and glycosyl chains are important factors affecting intracellular transport. These compounds are also associated with aging and advanced glycation are risk factors for AD. Thus, this study should further understanding of the pathology of AD. [ABSTRACT FROM AUTHOR]

HIV-associated dementia (HAD) is associated with amyloid-beta (Aβ) deposition. This study measured CSF and plasma amyloid beta-42 (Aβ-42), neprilysin (NEP) and cytokine levels in HIV-related cognitive impairments (HCI), HIV normal cognitive functioning (NF) and non-HIV controls. Our data showed a trend towards detectable plasma Aβ-42 levels more frequently in HCI (67%), when compared to NF (29%) and controls (10%). We showed elevated IL-8 levels in CSF of HCI compared to NF, although not significant values. The data from this pilot study indicates that CSF IL-8 and plasma Aβ-42 may be interesting biomarkers for the presence of HCI. [ABSTRACT FROM AUTHOR]

Abstract: In light of our previous observation of higher levels of cerebrospinal fluid (CSF) amyloid beta-42 (Aβ42) and CSF/serum albumin ratio in major depressive disorder (MDD), we analyzed two additional CSF biomarkers reflecting neurodegeneration—neurofilament protein light (NFL) and glial fibrillary acidic protein (GFAp)—in relationship to prevalent geriatric depression. Neuropsychiatric, physical, and lumbar puncture examinations, with DSM-III-R-based depression diagnoses and measurement of CSF levels of NFL and GFAp, were evaluated among a population-based sample of 78 elderly women (mean age, 73.9±3.2 years) without dementia for at least 10 years after CSF collection. Eleven (13.1%) women had MDD, and higher levels of NFL compared with women without depression. A multivariate model including age, NFL, Aβ42 and the CSF/serum albumin ratio showed that each biomarker was independently and positively associated with MDD, and that this biomarker profile explained more variation in the model compared with single or combined biomarkers. A CSF profile with higher levels of NFL, Aβ42, and CSF/serum albumin ratio may indicate neuropathological and vascular events in depression etiology. This contrasts with the well-characterized pattern of low Aβ42, higher CSF/serum albumin ratio, and higher NFL in Alzheimer''s disease. [Copyright &y& Elsevier]

Amyloid beta (Aβ) is a peptide responsible for the development of Alzheimer's disease (AD). Misfolding and accumulation of endogenous Aβ can lead to neural cell apoptosis through endoplasmic reticulum (ER) stress. Added exogenous Aβ can also result in ER stress, leading to neurotoxicity and apoptosis, which is identical to that caused by the endogenous peptide. We have speculated that the endocytic transport of Aβ causes ER stress and have previously shown that the oxysterol, in particular, 7-ketocholesterol (7-keto) induces more surface interaction between Aβ-42 and Jurkat cells than cholesterol. However, the interaction was not enough to induce intracellular transfer of the peptide. In this study, we investigated the effect of another oxysterol, 25-hydroxycholesterol (25-OH) on the membrane raft-dependent transport of Aβ-42 in Jurkat cells. Interestingly, intracellular transfer of Aβ-42 was observed in the presence of 25-OH only after the inclusion of cholera toxin B subunit (CT-B), a marker used to detect the raft domain. We speculated that 25-OH can induce intracellular movement of Aβ peptides. Furthermore, CT-B together with GM1 provided negative curvature, which resulted in the intracellular transport of Aβ-42. Notably, we used a protofibrillar species of Aβ-42 in this study. We have shown that the transport was microtubule-dependent since it could not be observed in depolymerized microtubules. These results demonstrate that oxysterols and glycosyl chains are important factors affecting intracellular transport. These compounds are also associated with aging and advanced glycation are risk factors for AD. Thus, this study should further understanding of the pathology of AD.