Distance-based β-amyloid protein detection on PADs for scanning and subsequent follow up of Alzheimer’s disease in human urine sample

We report on the first development of a simple distance-based β-amyloid (Aβ) protein quantification using paper-based devices (dPADs) to screen for Alzheimer’s disease (AD) and to subsequently follow up on...

Post-Ischemic Neurodegeneration of the Hippocampus Resembling Alzheimer’s Disease Proteinopathy

In this review, we summarize, inter alia, the protein and gene changes associated with Alzheimer’s disease and their role in post-ischemic hippocampal neurodegeneration. In the hippocampus, studies have revealed dysregulation of the genes for the amyloid protein precursor metabolism and tau protein that is identical in nature to Alzheimer’s disease. Data indicate that amyloid and tau protein, derived from brain tissue and blood due to increased permeability of the blood–brain barrier after ischemia, play a key role in post-ischemic neurodegeneration of the hippocampus, with concomitant development of full-blown dementia. Thus, the knowledge of new neurodegenerative mechanisms that cause neurodegeneration of the hippocampus after ischemia, resembling Alzheimer’s disease proteinopathy, will provide the most important therapeutic development goals to date.

Gold nanoparticles from magnetite for the detection of amyloid proteins in neurodegenerative diseases

Introduction. Currently, neurodegenerative diseases (ND) are the fourth leading cause of death worldwide that pose a great challenge in the development of tools for early diagnosis. Thus, advances in science seek sensitive and selective detection systems and this manuscript will highlight the importance of nanotechnology. Material and methods. A literature review was conducted on the representative findings of NPs technologies in neurodegenerative diseases. Articles written in both English and Spanish were included. References between 2015-2021 were also taken into account. Results. One of the most representative techniques, AuNP was specifically implemented, together with a magnetic center composed of magnetite, which has as a specific ligand with a C-terminal cysteine domain present in the B-amyloid protein, which adhere directly to the surface of the NPs, characterizing the anomalous protein. Subsequently, by means of nanosensors capable of detecting and measuring different concentrations, these pathologies are identified at an early stage. Conclusions. Today, along with the advent of biotechnology, it has been possible to design techniques with NPs that allow the identification of specific mutations and provide diagnosis in individuals. In the investigative models of AuNP, it is possible to infer that the capabilities that make them representative focus on their magnetism and biofunctionality, by specifically binding to amyloid peptides and other ligands present in the protein, which are the major components of amyloid plaques used in these studies.

Calcium Ions Aggravate Alzheimer’s Disease Through the Aberrant Activation of Neuronal Networks, Leading to Synaptic and Cognitive Deficits

Alzheimer’s disease (AD) is a neurodegenerative disease that is characterized by the production and deposition of β-amyloid protein (Aβ) and hyperphosphorylated tau, leading to the formation of β-amyloid plaques (APs) and neurofibrillary tangles (NFTs). Although calcium ions (Ca2+) promote the formation of APs and NFTs, no systematic review of the mechanisms by which Ca2+ affects the development and progression of AD has been published. Therefore, the current review aimed to fill the gaps between elevated Ca2+ levels and the pathogenesis of AD. Specifically, we mainly focus on the molecular mechanisms by which Ca2+ affects the neuronal networks of neuroinflammation, neuronal injury, neurogenesis, neurotoxicity, neuroprotection, and autophagy. Furthermore, the roles of Ca2+ transporters located in the cell membrane, endoplasmic reticulum (ER), mitochondria and lysosome in mediating the effects of Ca2+ on activating neuronal networks that ultimately contribute to the development and progression of AD are discussed. Finally, the drug candidates derived from herbs used as food or seasoning in Chinese daily life are summarized to provide a theoretical basis for improving the clinical treatment of AD.

A Stepwise Data Interpretation Process For Renal Amyloidosis Subtyping by LMD-MS

Backgrounds: Systemic amyloidosis is classified according to the deposited amyloid protein, which determines its best therapeutic scheme. The laser microdissection combined with mass spectrometry (LMD-MS) technique is a promising approach for precise subtyping of amyloidosis, however, is hampered by how to interpret the MS data.Objectives: The objective of the present study is to establish a complete data interpretation procedure for LMD-MS based amyloidosis subtyping.Methods: Formalin fixed paraffin-embedded specimens from patients with renal amyloidosis were analyzed by LMD-MS for proteome quantification. Forty-two specimens were used for training the data interpretation procedure, which was validated by another 50 validation specimens. Area under receiver operating curve (AUROC) analysis of amyloid accompanying proteins (APOE, APOA4 and SAMP) for discriminating amyloidosis from non-amyloid nephropathies was performed.Results: A stepwise data interpretation procedure that include or exclude the subtypes group by group was established, in which, involvement of non-immunoglobulin amyloid protein is determined by P-score, involvement of immunoglobulin light chain is determined by variable of λ-κ, and immunoglobulin heavy chain’s participation is judged by H-score. This data interpretation method achieved a 88% accuracy in 50 validation specimens. The amyloid accompanying proteins showed significant quantitative differences between amyloidosis specimens and non-amyloid nephropathies. Each of the single accompanying protein had a AUROC value more than 0.9 for diagnosis of amyloidosis from non-amyloid control, and the averaged value of spectral count of the three accompanying proteins showed the highest AUROC (0.966), indicating it might be an alternative indicator for amyloidosis diagnosis.Conclusions: The proteomic data interpretation procedure for amyloidosis subtyping based on LMD-MS was established successfully, which has high clinical application value.

Effect of Gene Editing on Alzheimer's Disease

Background Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and, eventually, the ability to carry out the simplest tasks. In most people with Alzheimer’s, symptoms first appear in their mid-60s. Current estimates suggest that 44 million people live with dementia worldwide at present. This is predicted to more than triple by 2050 as the population ages. Alzheimer’s disease is currently ranked as the sixth leading cause of death in the United States, but recent estimates indicate that the disorder may rank third, just behind heart disease and cancer, as a cause of death for older people Treatment is currently targeted toward symptomatic therapy, although trials are underway that aim to reduce the production and overall burden of pathology within the brain. Recently, the Clustered Regular Interspaced Short Palindromic Repeats (CRISPR-cas9) has shown promise in certain neurological disorders, it provides a precise editing to human genome and reflect an efficient curative therapy. We aimed to investigate the efficacy of knock-out of the APP gene “Amyloid precursor protein gene(APBA2)that consequently modify the expression of Amyloid protein in leucocytes cell line using CRISPR-cas9 technology. Methods The gene expression profile of Alzheimer's disease was downloaded from biological bioinformatics databases,and based on bioinformatics analysis, we figured out that APP gene was overexpressed in Alzheimer's disease in both brain and peripheral tissues such as plasma, fibroblast and PMNLs. We used PMNLs as the source of gene for edition in our study .We knocked out the APP gene in leucocytes cell lines using CRISPR-cas9 technology. Finally, the gene editing efficacy was evaluated by cell viability assay, the gene expression was measured by qPCR and the Amyloid protein expression was proved by Immunofluorescence. Results knockout of APP gene int Leucocytes Cell line resulted in reduction in cell viability that was associated with marked reduction in the amyloid protein and gene expressions. Conclusion knockout of APP(APBA2) gene represents a promising therapeutic strategy in Alzheimer's disease.