Types Of Fibrils Research Articles

Interaction with zinc oxide nanoparticle kinetically traps α-synuclein fibrillation into off-pathway non-toxic intermediates

α-Synuclein is an intrinsically disordered amyloidogenic protein associated with Parkinson's disease (PD). The monomeric α-synuclein transition into amyloid fibril involves multiple steps, which are affected by several intrinsic and extrinsic factors. This increases complexities in development of targeted therapeutics against the pathological intermediate(s). Several studies have been dedicated to find an effective molecule to inhibit the detrimental amyloidogenesis. In recent years, metal oxide nanoparticle interfaces have shown direct effects on protein conformation, hence may be adopted as an alternative potential therapeutic approach against amyloidosis. In this context, our study explores the zinc oxide nanoparticle (ZnONP) with negative surface potential interface interaction with α-synuclein, and subsequent impact of the interaction on the protein fibrillation and the fibril-mediated cytotoxicity. N-terminus amphipathic “KA/TKE/QGV” repeating motifs in α-synuclein primarily interact with the ZnONP interface that enthalpically drives initial adsorption of the protein onto the interface. Whereas, subsequent bulk-protein adsorption onto the hard-corona is entropically driven, leading into flocculation of the complex. The flocs appear as amorphous mesh-like morphology in TEM micrographs, as opposed to the typical fibrils formed by the wild-type protein. Interestingly, α-synuclein in complex with ZnONP shows significantly lowered cytotoxicity against the IMR32 and THP-1 cells in-vitro, as compared to fresh α-synuclein.

Effects of phosphate ion concentration on in-vitro fibrillogenesis of sturgeon type I collagen

Nonmammalian collagens have attracted significant attention owing to their potential for use as a source of cell scaffolds for tissue engineering. Since the morphology of collagen fibrils controls cell proliferation and differentiation, its regulation is essential for fabricating scaffolds with desirable characteristics. In this study, we evaluated the effects of the phosphate ion (Pi) concentration on the characteristics of fibrils formed from swim bladder type I collagen (SBC) and skin type I collagen (SC) from the Bester sturgeon. An increase in the Pi concentration decreased the fibril formation rate, promoted the formation of thick fibrils, and increased the thermal stability of the fibrils for both SBC and SC. However, the SBC and SC fibrils exhibited different fibril formation rates, degrees of fibrillogenesis, morphologies, and denaturation temperatures for the same reaction conditions. Finally, by regulating the Pi concentration, various types of SBC and SC fibrils could be coated on cell culture wells, and fibroblasts could be cultured on them. The results showed that thin fibrils enhance fibroblast extension and proliferation, whereas thick fibrils restrain fibroblast extension but orient them in the same direction. The results of this study suggest that SBC fibrils, which exhibit diverse morphologies, are suitable for use as a novel scaffold material, whose characteristics can be tailored readily by varying the Pi concentration.

Proanthocyanidin-crosslinked collagen/konjac glucomannan hydrogel with improved mechanical properties and MRI trackable biodegradation for potential tissue engineering scaffolds.

Collagen (Col) has been intensively exploited as a biomaterial for its excellent biocompatibility, biodegradation and bioactivity. However, the poor mechanical properties and rapid biodegradation of reconstituted collagen hydrogels have always been the bottlenecks for their further development especially for vascular tissue engineering. Herein, based on the self-assembly characteristics of collagen, a ternary hydrogel scaffold, comprising rigid collagen molecules, flexible konjac glucomannan (KGM) chains and biocompatible crosslinkers of proanthocyanidin (PA), has been designed to achieve a synergistic interaction for essentially optimizing the mechanical properties of the so-obtained Col/KGM/PA hydrogel, which possesses not only substantially improved strength but also good elasticity. PA endows these scaffolds with controllable biodegradation and anti-calcification and antioxidant activities. TEM discovered the co-existence of two types of fibrils with distinctly different arrangement patterns, explaining the contribution of KGM macromolecules to elasticity generation. The in vivo variations of Col/KGM/PA implants are visualized in real-time by magnetic resonance imaging (MRI). Moreover, a quantitative technique of MRI T2-mapping combined with histology is designed to visualize the in vivo biodegradation mechanism of layer-by-layer erosion for these hydrogels. Simultaneously, three different relationships between the respective processes of in vivo degradation and in vivo dehydration of these controlled hydrogel implants were clearly revealed by this technique. Such a designed Col/KGM/PA composite hydrogel realizes the essential integration of good biocompatibility, controllable biodegradation and improved mechanical properties for developing a desired scaffold material for tissue engineering applications.

The apparent mechanical effect of isolated amyloid-β and α-synuclein aggregates revealed by multi-frequency MRE.

Several biological processes are involved in dementia, and fibrillar aggregation of misshaped endogenous proteins appears to be an early hallmark of neurodegenerative disease. A recently developed means of studying neurodegenerative diseases is magnetic resonance elastography (MRE), an imaging technique investigating the mechanical properties of tissues. Although mechanical changes associated with these diseases have been detected, the specific signal of fibrils has not yet been isolated in clinical or preclinical studies. The current study aims to exploit the fractal-like properties of fibrils to separate them from nonaggregated proteins using a multi-frequency MRE power law exponent in a phantom study. Two types of fibril, α-synuclein (α-Syn) and amyloid-β (Aβ), and a nonaggregated protein, bovine serum albumin, used as control, were incorporated in a dedicated nondispersive agarose phantom. Elastography was performed at multiple frequencies between 400 and 1200Hz. After 3D-direct inversion, storage modulus (G'), phase angle (ϕ), wave speed and the power law exponent (y) were computed. No significant changes in G' and ϕ were detected. Both α-Syn and Aβ inclusions showed significantly higher y values than control inclusions (P = 0.005) but did not differ between each other. The current phantom study highlighted a specific biomechanical effect of α-Syn and Aβ aggregates, which was better captured with the power law exponent derived from multi-frequency MRE than with single frequency-derived parameters.

Characterizing highly fibrillated nanocellulose by modifying the gel point methodology

The characterization of nanocellulose fibres (NC) length is a difficult and indirect measurement which relies on aspect ratio calculation and fibre diameter analysis. The aspect ratio can be directly calculated from the gel point, a parameter obtained from sedimentation experiments. The gel point has been used with macroscopic fibres and microfibrillated cellulose, that easily sediment by gravity. However, this methodology has not yield consistent results with highly charged nanofibres nor with fibres with sediment layer difficult to observe. In this study, the gel point methodology is modified: 1) dying the fibres with Crystal Violet to enable the visualization of the fibrils sedimentation line without affecting the fibre network; and 2) by optimizing the sedimentation time to ensure complete settling. The two types of fibrils characterized -low and high fibrillated NC (LF-NC, HF-NC)- behave differently due to the slower sedimentation of HF-NC. The time to reach a stable sedimented layer increases with the level of fibre fibrillation, the charge and the decrease of fibre dimension. Reproducible gel point can be measured after 2 days for LF-NC; however, 8 days are required for HF-NC. The modified methodology was validated by quantifying the influence of pH and salt concentration. As expected, low pHs and the addition of CaCl2 coagulate HF-NC into flocs which increase the ratio: final over initial fibres height (Hs/Ho); this decreases significantly the gel point, as a lower amount of HF-NC are required to interconnect all fibres. This modified method is a valuable tool for the accurate dimensional characterisation of highly charged and low diameter cellulose nanofibres.

EGFP insertional mutagenesis reveals multiple FXR2P fibrillar states with differing ribosome association in neurons.

ABSTRACTRNA-binding proteins (RBPs) function in higher-order assemblages such as RNA granules to regulate RNA localization and translation. The Fragile X homolog FXR2P is an RBP essential for formation of neuronal Fragile X granules that associate with axonal mRNA and ribosomes in the intact brain. However, the FXR2P domains important for assemblage formation in a cellular system are unknown. Here we used an EGFP insertional mutagenesis approach to probe for FXR2P intrinsic features that influence its structural states. We tested 18 different in-frame FXR2PEGFP fusions in neurons and found that the majority did not impact assemblage formation. However, EGFP insertion within a 23 amino acid region of the low complexity (LC) domain induced FXR2PEGFP assembly into two distinct fibril states that were observed in isolation or in highly-ordered bundles. FXR2PEGFP fibrils exhibited different developmental timelines, ultrastructures and ribosome associations. Formation of both fibril types was dependent on an intact RNA-binding domain. These results suggest that restricted regions of the LC domain, together with the RNA-binding domain, may be important for FXR2P structural state organization in neurons.

Self-assembled collagen fibrils from the swim bladder of Bester sturgeon enable alignment of MC3T3-E1 cells and enhance osteogenic differentiation.

Collagen is the most abundant protein in animals, and its polymer, collagen fibrils, regulate cellular proliferation, differentiation, and migration. Low antigenicity, biocompatibility, and biodegradability make collagen fibrils suitable functional scaffolds for tissue engineering. In a previous study, we found that the type I atelocollagen purified from the swim bladder of Bester sturgeon (swim bladder collagen, SBC) showed high fibril-forming ability, producing thicker fibrils faster than porcine collagen. In this study, we report a novel method to coat cell culture wells with highly aligned collagen fibrils using the SBC. Two types of fibrils with different thicknesses were prepared by changing the crosslinking treatment timing. The oriented, thick collagen fibrils induced pre-osteoblastic MC3T3-E1, pre-adipocytic 3T3-L1, pre-myocytic C2C12, and fibroblastic L929 cells to align in the same direction, whereas the oriented, fine fibrils made a cell network with their long pseudopods. Cellular proliferation was inhibited on both fibrils. Furthermore, both fibrils induced the early differentiation of MC3T3-E1 cells without differentiation stimuli. In contrast, the morphology of pre-chondrocytic ATDC5 cells on both fine and thick fibrils extended very short pseudopods and continued to maintain a spherical shape without stretching, suggesting a distinct effect by the fibrils. The newly developed fibril coatings are in the form of a thin film, thereby providing good visibility of the cell structure, including cell-cell and cell-ECM interactions, using a phase contrast microscope. The fibril coatings have high potential as a useful tool for tissue engineering research.

Transthyretin Glu54Leu – an unknown mutation within the Swedish population associated with amyloid cardiomyopathy and a unique fibril type

For the first time, we report of a Swedish family of five individuals with a TTR Glu54Leu (p. Glu74Leu) mutation in the transthyretin gene. This mutation has been previously described a few times in the literature, but no phenotypic or clinical description has been done before. The most common mutation in the Swedish population is TTRVal30Met and is mostly found in the Northern part of Sweden. Interestingly, the TTRGlu54Leu mutation was found in the same endemic area. The main phenotype of the TTR Glu54Leu patients is severe cardiomyopathy, which resulted in heart transplantation for the index person. As previously seen for ATTR amyloidosis patients with mainly cardiomyopathy, the amyloid fibrils consisted of a mixture of full-length and fragmented TTR species. However, western blot analyses detected a previously unrecognized band, indicating that these patients may have a third, so far unrecognized, fibril composition type that is distinct from the usual type A band pattern.

Network-Based Classification and Modeling of Amyloid Fibrils.

Amyloid fibrils are locally ordered protein aggregates that self-assemble under a variety of physiological and in vitro conditions. Their formation is of fundamental interest as a physical chemistry problem and plays a central role in Alzheimer's disease, Type II diabetes, and other human diseases. As the number of known amyloid fibril structures has grown, the need has arisen for a nomenclature for describing and classifying fibril types, as well as a theoretical description of the physics that gives rise to the self-assembly of these structures. Here, we introduce a systematic nomenclature and coarse-graining methodology for describing the topology of fibrils and other protein aggregates, along with a computational methodology for simulating protein aggregation. Both have mathematical underpinnings in graph theory and statistical mechanics and are consistent with available experimental data on the fibril structure and aggregation kinetics. Our graph representation of the fibril topology enables us to define a network Hamiltonian based on connectivity patterns among monomers rather than detailed intermolecular interactions, greatly speeding up the simulation of large ensembles. Our simulation strategy is capable of recapitulating the formation of all currently known amyloid fibril topologies found in the Protein Data Bank, as well as the formation kinetics of fibrils and oligomers.

2-Hexadecenal inhibits growth of C6 glioma cells.

2-Hexadecenal (2HD) formation in the organism occurs via irreversible enzymatic degradation of sphingosine-1-phosphate or nonenzymatic γ-, UV-, or HOCl-induced destruction of a number of sphingolipids including S1P. The current research focuses on the study of 2HD effects on C6 glioma cells growth. The results obtained show that 2HD causes a dose-dependent decrease in proliferative and mitotic indices. The change in the mitotic index is due to the redistribution of cells in the different phases of mitosis. These processes are accompanied by cytoskeleton rearrangement and changes in cell morphology, which are expressed in F-actin redistribution, change in the number and type of filopodia and fibrils, leading to cell shape changes, decrease in intercellular contacts and monolayer rarefaction. Cells treatment with 2HD leads to apoptosis induction and signalling pathways modification, including activation of JNK, p38, and ERK1/2 MAPK but not PI3K. The effects observed are not related to the cytotoxicity of 2HD. Significance of the study: 2HD-an unsaturated aldehyde, which level can rise under conditions of oxidative stress as a result of nonenzymatic sphingolipids' destruction. The mechanisms of 2HD action on various cell types have not been sufficiently studied. Therefore, the study on functional role of this aldehyde in different cell types that may be its target is relevant. This study demonstrated that 2HD inhibits growth of C6 glioma cells due to modification of intracellular processes of signal transduction, cytoskeleton rearrangement, change in the mitotic regimen and apoptosis induction.

Spectroscopic Evidence of Tertiary Structural Differences Between Insulin Molecules in Fibrils

Protein fibrils are of great interest due to their involvement in several pathologies and their roles in the degradation of many therapeutic protein products. Fibrils share highly similar secondary structural motifs across different proteins and applied stress conditions. However, fibril morphology differs according to the surrounding conditions, with aromatic and hydrophobic amino acids playing important roles in mature fibril formation. In this study, we use Raman microscopy, by means of the aromatic amino acids in insulin molecules as markers, to probe for tertiary structure differences within fibrils. We compared 2 different fibril types, linear fibril bundles and spherulites. Generation of linear fibril bundles was undertaken in an acetic acid–containing formulation, whereas spherulites were generated in a hydrochloric acid–containing formulation. The Raman intensities of tyrosine and phenylalanine side chains suggest that there are significant differences between the fibril bundles. The findings suggest that the insulin components of the fibril strands are not arranged identically in the 2 fibril types and that this gives rise to differences in their tertiary structures. Overall, the work indicates that the physicochemical properties of fibril structures can be altered by changing the formulation and that these alterations can be monitored by Raman spectroscopy.

Conservation of the Amyloid Interactome Across Diverse Fibrillar Structures

Several human proteins cause disease by misfolding and aggregating into amyloid fibril deposits affecting the surrounding tissues. Multiple other proteins co-associate with the diseased deposits but little is known about how this association is influenced by the nature of the amyloid aggregate and the properties of the amyloid-forming protein. In this study, we investigated the co-aggregation of plasma and cerebrospinal proteins in the presence of pre-formed amyloid fibrils. We evaluated the fibril-associated proteome across multiple amyloid fibril types that differ in their amino acid sequences, ultrastructural morphologies, and recognition by amyloid-binding dyes. The fibril types included aggregates formed by Amyloid β, α-synuclein, and FAS4 that are associated with pathological disorders, and aggregates formed by the glucagon and C-36 peptides, currently not linked to any human disease. Our results highlighted a highly similar response to the amyloid fold within the body fluid of interest. Fibrils with diverse primary sequences and ultrastructural morphologies only differed slightly in the composition of the co-aggregated proteins but were clearly distinct from less fibrillar and amorphous aggregates. The type of body fluid greatly affected the resulting amyloid interactome, underlining the role of the in vivo environment. We conclude that protein fibrils lead to a specific response in protein co-aggregation and discuss the effects hereof in the context of amyloid deposition.

Protein oxidation during temperature-induced amyloid aggregation of beta-lactoglobulin

Although the connection between protein oxidation, amyloid aggregation and diseases such as Alzheimer’s is well known there is no information on such effects during preparation of beta-lactoglobulin fibrils. Different morphologies of amyloid aggregates of beta-lactoglobulin were prepared by incubation at pH 2 or pH 3.5 for up to 72 h. After 5 h, amyloid aggregates at pH 2 formed typical fibrils, which consisted of peptides. At pH 3.5, the amyloid aggregates were worm-like and consisted of intact protein. After 72 h, the building blocks at both pH values changed towards smaller peptides. The apparent tyrosine oxidation reached a maximum after 5 h at both pH values, whereas N-formylkynurenine and carbonyls increased continuously during 72 h. In case amyloid structures are used as edible material, the health related effects caused by protein oxidation needs to be considered.

The Effect of Preadsorbed Polyelectrolytes on the Surface Properties and Dispersity of Clay Minerals and Soils

On the basis of adsorption studies, the characteristics of formation of polyelectrolyte (PE) nanoadsorption layers of an aliphatic structure that creates a mineral–organic matrix on clay minerals and soils (kaolinite, montmorillonite, quartz sand, and gray forest and chernozem soils) surfaces have been revealed. It has been established that the polyacrylamide (PAM) and polyacrylic acid (PAA) adsorption limit values on all minerals are significantly higher than the calculated values for the single-layer formation. This indicates the surface adsorption of not only individual macromolecules, but also of secondary PE structures of types of bundles or fibrils determining the cluster-matrix structure of the modified surface. The study of the electric surface properties (electrophoretic mobility, electrokinetic potential, рН, and electroconductivity) of adsorption-modified PE suspensions of minerals and soils has corroborated that there are differences in the adsorption mechanism, ranging from physical to chemisorption with the formation of surface compounds, as a result of both differences between PE polar groups and the mineral type. It has been demonstrated that the mineral and soil surface modification by organic substances differently affects the dispersity, porosity, mean pore radii, total surface area, and pore volume in the direction of both an increase and decrease in size. Here, this results in significant changes in the differential pore volume and more homogeneous pore size distribution.

Amyloid fibril composition within hereditary Val30Met (p. Val50Met) transthyretin amyloidosis families.

BackgroundThe amyloid fibril in hereditary transthyretin (TTR) Val30Met (pVal50Met) amyloid (ATTR Val30Met) amyloidosis is composed of either a mixture of full-length and TTR fragments (Type A) or of only full-length TTR (Type B). The type of amyloid fibril exerts an impact on the phenotype of the disease, and on the outcome of diagnostic procedures and therapy. The aim of the present study was to investigate if the type of amyloid fibril remains the same within ATTR Val30Met amyloidosis families.MethodsFifteen families were identified in whom at least two first-degree relatives had their amyloid fibril composition determined. The type of ATTR was determined by Western blot in all but two patients. For these two patients a positive 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy indicated ATTR Type A.ResultsIn 14 of the 15 families, the same amyloid fibril composition was noted irrespective of differences in age at onset. In the one family, different ATTR fibril types was found in two brothers with similar ages at onset.ConclusionsFamily predisposition appears to have an impact on amyloid fibril composition in members of the family irrespective of their age at onset of disease, but if genetically determined, the gene/genes are likely to be situated at another location than the TTR gene in the genome.

Understanding the Molecular Parameters Determining the Pathological Properties of Amyloid Fibrils

Transmission of amyloid fibrils in the brain via a prion-like mechanism is a major feature of various neurodegenerative diseases. In this context, it is crucial to understand the mechanism by which amyloid fibrils of tau can act to seed the growth of fibrils from native tau. During fibril growth native protein is converted into multiple misfolded aggregated conformations, each being a strain that propagates faithfully and which is linked to a specific disease. An understanding of the molecular mechanism of template-driven conversion of native soluble protein into structurally different type of fibrils will lead to a better understanding in general of molecular parameters which determine the pathological properties of amyloid fibrils in various neurodegenerative diseases, and will help in development of therapeutics for various protein aggregation diseases. In this study, the molecular mechanism of template-driven growth of the tau fibrils is shown to be describable by a simple Michaelis-Menten-like two-step model, in which monomers act like the substrate, and fibrils act like the enzyme. In the first step, monomer attaches to the ends of fibrils, and in the second rate limiting step, the conformational transition takes place. Modeling tau fibril growth to such a simple model provides a mechanistic rationale for the asymmetric seeding barrier which exists between two isoforms of the tau protein. Importantly, tau-4R and 3R are found to form structurally different fibrils: the structural core is more ordered in tau-3R fibrils than in tau-4R fibrils. These results provide a structural rationale forthe asymmetric seeding barrier. Hence, the current study provides a detailed understanding of the molecular parameters which determine the pathological properties of amyloid fibrils.

Network-Based Modeling of Amyloid Fibril Formation

Amyloid fibrils are locally ordered protein aggregates that self-assemble under a variety of physiological and in vitro conditions. Their formation is of fundamental interest due to its central role in Alzheimer's disease, Type II diabetes, and other human diseases. As the number of known amyloid fibril structures has grown, the need has arisen for a nomenclature for describing and classifying fibril types, as well as a theoretical description of the physics that gives rise to the self-assembly of these structures. We have developed a systematic nomenclature and coarse-graining methodology for describing the topology of fibrils and other protein aggregates, along with a computational methodology for simulating protein aggregation on the scale of thousands of monomers interacting on the timescale of hours. Our coarse-graining methodology has mathematical underpinnings in both graph theory and statistical mechanics, providing the foundation upon which we have built software capable of both quantitatively mapping fibril topology from atomistic structures, and simulating their formation from a set of free monomers via either thermodynamic sampling using Markov chain Monte Carlo (MCMC) sampling, or time-dependent sampling based in generalized Arrhenius kinetics. Our simulation strategy is capable of recapitulating the formation of all currently known amyloid fibril topologies found in the Protein Data Bank, as well as the formation kinetics of fibrils and oligomers.

Induced Lanthanide Circularly Polarized Luminescence as a Probe of Protein Fibrils.

Protein fibrils are involved in a number of biological processes. Because their structure is very complex and not completely understood, different spectroscopic methods are used to monitor different aspects of fibril structure. We have explored circularly polarized luminescence (CPL) induced in lanthanide compounds to indicate fibril growth and discriminate among fibril types. For hen egg-white lysozyme and polyglutamic acid-specific CPL, spectral patterns were obtained and could be correlated with vibrational circular dichroism (VCD) spectra and thioflavin T fluorescence. The CPL spectra were measured on a Raman optical activity spectrometer, and its various polarization modes are discussed. The experiments indicate that the induced CPL is sensitive to more local aspects of the fibril structure than VCD. For CPL, smaller amounts of the sample are required for the analysis, and thus this method appears to be a good candidate for future spectroscopic characterization of these peptide and protein aggregates.

Sterile Capsule-Egg Cocoon Covering Constitutes an Antibacterial Barrier for Spider Parasteatoda tepidariorum Embryos.

Coexistence of organisms and pathogens has resulted in the evolution of efficient antimicrobial defense, especially at the embryonic stage. This investigation aimed to substantiate the hypothesis that the layers of silk in a spider cocoon play a role in the immunity of the embryos against microorganisms present in the external environment. A two-step interdisciplinary attempt has been made. First, the eggs and empty cocoons of the spider Parasteatoda tepidariorum were incubated on lysogeny broth agar media for 3 d. In the samples of eggs, no growth of bacteria was detected. This indicated that the eggs inside cocoons were sterile. Therefore, in the second step, the cocoons and egg surface were analyzed using SEM, TEM, and LM. The obtained images demonstrated that both inner and outer layers of the silk are built of threads of the same diameter, set in an irregular manner, and randomly clustered into groups. The threads in the outer layer were packed more densely than in the inner one. TEM analysis revealed threads of two types of fibrils and their arrangement. The resultant thread tangle of the cocoon, possibly correlated with the ultrastructure of the fibers, seems to be an example of a structure-function relationship playing a crucial ecoimmunological role in spider embryonic development.

Electrochemistry of Alzheimer Disease Amyloid Beta Peptides.

Alzheimer's disease (AD) is a widespread form of dementia that is estimated to affect 44.4 million people worldwide. AD pathology is closely related to the accumulation of amyloid beta (Aβ) peptides in fibrils and plagues, the small oligomeric intermediate species formed during the Aβ peptides aggregation presenting the highest neurotoxicity. This review discusses the recent advances on the Aβ peptides electrochemical characterization. The Aβ peptides oxidation at a glassy carbon electrode occurs in one or two steps, depending on the amino acid sequence, length and content. The first electron transfer reaction corresponds to the tyrosine Tyr10 amino acid residue oxidation, and the second to all three histidine (His6, His13 and His14) and one methionine (Met35) amino acid residues. The Aβ peptides aggregation and amyloid fibril formation are electrochemically detected via the electroactive amino acids oxidation peak currents decrease that occurs in a time dependent manner. The Aβ peptides redox behaviour is correlated with changes in the adsorption morphology from initially random coiled structures, corresponding to the Aβ peptide monomers in random coil or in α-helix conformations, to aggregates, protofibrils and two types of fibrils, corresponding to the Aβ peptides in a β-sheet configuration, observed by atomic force microscopy. Electrochemical studies of Aβ peptides aggregation, mediated by the interaction with metal ions, particularly zinc, copper and iron, and different methodologies concerning the detection of Aβ peptide biomarkers of AD in biological fluids, using electrochemical biosensors, are also discussed.