Β-amyloid Fragment Research Articles

Montelukast Ameliorates Scopolamine-induced Alzheimer's Disease: Role on Cholinergic Neurotransmission, Antioxidant Defence System, Neuroinflammation and Expression of BDNF.

Alzheimer's disease (AD) is an overwhelming neurodegenerative disease with progressive loss of memory. AD is characterized by the deposition of the senile plaques mainly composed of β-amyloid (Aβ) fragment, BDNF decline, Cholinergic system overactivity and neuroinflammation. Montelukast (MTK), a leukotriene receptor antagonist, showed astounding neuroprotective effects in a variety of neurodegenerative disorders. This study aims to investigate the ameliorative effects of Montelukast in the scopolamineinduced Alzheimer's disease (AD) model in rats and evaluate its activity against neuroinflammation. Thirty rats were split into five groups: Control group (1 mL/kg normal saline, i.p.), Montelukast perse (10 mg/kg, i.p.), Disease group treated with Scopolamine (3 mg/kg, i.p.), Donepezil group (3 mg/kg, i.p.), Montelukast treatment group (10 mg/kg, i.p.) and behavioural and biochemical tests were carried out to assess the neuro protective effect. Scopolamine treatment led to a significant reduction in learning and memory and an elevation in cholinesterase levels when compared with the control group (p < 0.01). Additionally, elevated oxidative stress and Amyloid-β levels were associated with enhanced neuroinflammation (p < 0.05, p < 0.01). Furthermore, the decline in neurotrophic factor BDNF is also observed when compared with the normal control group (p < 0.01). Montelukast pre-treatment significantly attenuated learning and memory impairment and cholinesterase levels. Besides, Montelukast and standard drug donepezil administration significantly suppressed the oxidative stress markers (p < 0.01), Amyloid-β levels, neuroinflammatory mediators (p < 0.05) and caused a significant increase in BDNF levels (p < 0.05). Montelukast bestowed ameliorative effects in scopolamine-induced AD animal models as per the previous studies via attenuation of memory impairment, cholinesterase neurotransmission, oxidative stress, Amyloid-β levels, neuroinflammatory mediators and enhanced BDNF levels.

Influence of TiO2 and ZnO Nanoparticles on α-Synuclein and β-Amyloid Aggregation and Formation of Protein Fibrils

The most common neurological disorders, i.e., Parkinson's disease (PD) and Alzheimer's disease (AD), are characterized by degeneration of cognitive functions due to the loss of neurons in the central nervous system. The aggregation of amyloid proteins is an important pathological feature of neurological disorders.The aggregation process involves a series of complex structural transitions from monomeric to the formation of fibrils. Despite its potential importance in understanding the pathobiology of PD and AD diseases, the details of the aggregation process are still unclear. Nanoparticles (NPs) absorbed by the human circulatory system can interact with amyloid proteins in the human brain and cause PD. In this work, we report the study of the interaction between TiO2 nanoparticles (TiO2-NPs) and ZnO nanoparticles (ZnO-NPs) on the aggregation kinetics of β-amyloid fragment 1-40 (βA) and α-synuclein protein using surface-enhanced Raman spectroscopy (SERS) and tip-enhanced Raman spectroscopy (TERS). The characterizations of ZnO-NPs and TiO2-NPs were evaluated by X-ray diffraction (XRD) spectrum, atomic force microscopy (AFM), and UV-Vis spectroscopy. The interaction of nanoparticles with amyloid proteins was investigated by SERS. Our study showed that exposure of amyloid protein molecules to TiO2-NPs and ZnO-NPs after incubation at 37 °C caused morphological changes and stimulated aggregation and fibrillation. In addition, significant differences in the intensity and location of active Raman frequencies in the amide I domain were found. The principal component analysis (PCA) results show that the effect of NPs after incubation at 4 °C does not cause changes in βA structure.

Dopamine Improves Resistance of Dendrites of Mauthner Neurons to Destruction Induced by Sensory Stimulation and Application of Β-Amyloid.

Mauthner neurons in goldfish fry were studied by the methods of light and electron microscopy. The structure and volume of individual dendrites as well as the structure of axodendritic synapses were examined using virtual images of neurons formed from serial 3-μ sections. In short-time (5 h) experiments with application of dopamine, β-amyloid fragment (25-35), and long-term sensory stimulation affecting afferent inputs to Mauthner neurons, the dendrites were larger than the same dendrites under the same conditions without dopamine application. Application of dopamine induced no pathological changes in the structure of axodendritic chemical and electric synapses containing desmosome-like contacts.

Mechanisms of Regulation of Amyloid-Induced Permeability of Model Lipid Membranes by Polyphenols

This work is devoted to the study of the processes of formation and functioning of ion channels by amyloidogenic peptides, pathological aggregation and accumulation of which is a cause of neurodegenerative disorders. The effect of the plant polyphenols phloretin, butein, resveratrol, isoliquiritigenin, 4'-hydroxychalcone, and cardamonine on the pore-forming activity of β-amyloid peptide fragment 25–35 in bilayer lipid membranes from palmitoyl-phosphocholine was studied. It was demonstrated that the introduction of phloretin, butein or isoliquiritigenin in membrane-bathing solutions to a concentration of 20 µM leads to the increase of macroscopic transmembrane currents induced by peptide. At the same time, cardamonine, 4'-hydroxychalcone, and resveratrol have no effect on the activity of β-amyloid peptide fragment 25–35. The comparison of the results of studying the effect of tested polyphenols on electric and elastic properties of model membranes and pore-forming ability of β-amyloid peptide fragment 25–35 allowed it to concluded that there is no connection between the potentiating effect of phloretin, butein, or isoliquiritigenin and changes in the physicochemical properties of lipid bilayers. Results obtained by means of a confocal fluorescent microscopy indicate that the domain organization of the lipid bilayer may play a role in the pore-forming activity of amyloidogenic peptide. The results of electrophysiological measurements obtained for α-synuclein (another protein forming ion-permeable pores) do not contradict the hypothesis of binding of polyphenols, hydroxylated in the 7 position of the A cycle and in the 4'-position of the B cycle, with an open propane fragment with β-layers formed by amyloid peptides.

Compensatory Changes in Mauthner Neurons in Goldfish Induced by Sensory Stimulation and Application of β-Amyloid

Objectives. To study the structure and formation of Mauthner neuron dendrites in goldfish exposed to neurotoxic β-amyloid fragment 25–35 and prolonged sensory stimulation influencing the afferent inputs to these neurons. Materials and methods. Goldfish Mauthner neurons were studied by light and electron microscopy. Individual dendrites were identified, their volumes were determined, and synapse structure was assessed using virtual 3D images of Mauthner neurons obtained from serial sections of thickness 3 μm. The functional status of Mauthner neurons was evaluated indirectly from the motor lateralization of the fish. Results. Mauthner neurons responded to application of β-amyloid combined with subsequent prolonged sensory stimulation with decreases in the volume of the ventral dendrites, damage to their ultrastructure, and degeneration of a proportion of synapses. Degeneration of more active neurons was more significant than that of less active cells. Newly formed medial dendrites had greater volume and less damaged synapse ultrastructure than ventral dendrites. There were no differences in the sizes of specialized junctions between synapses of the same type on ventral and medial synapses. Conclusions. Medial dendrite formation is a compensatory reaction to dystrophy of the ventral dendrite due to the experimental treatment.

Hydrogel Formation by an Aromatic Analogue of a β-Amyloid Fragment, Aβ16–22: A Scaffold for 3D Cell Culture

A short 7-residue stretch from β-amyloid, Aβ16–22 (Ac-KLVFFAE-am), yields typical amyloid-like fibrils at neutral pH. The Phe–Phe cassette present in the peptide is believed to be critical for its self-assembly. We report that the aromatic analogue Aβ16–22(F20Y) forms self-supporting soft gels at concentrations ≥2 mM even though the end-capped parent peptide does not form hydrogel up to 20 mM (1.8% w/w) concentration. The hydrogel is made up of distinct amyloid-like fibers. The storage modulus of 20 mM gel is ∼3–5-fold higher than the loss modulus in the 2–3000 rad/s angular frequency range, indicating distinct elastic properties. The hydrogel supports the growth of rat pancreatic cells (RIN-5F), human embryonic kidney cells (HEK-293), baby hamster kidney cells (BHK-21), and human neuroblastoma cells (IMR-32). The cells grow in clusters as is anticipated in a three-dimensional matrix. The rat pancreatic cells produced insulin, suggesting that they are functional inside the gel.

The Effect of Toll‐Like Receptor‐4 on the Behavioral Impairment in Aβ1–42 Induced AD Mouse Model

ObjectiveTo investigate the role of toll like receptor 4 (TLR4) in the cognition impairment in β‐amyloid fragment 1–42 (Aβ1–42) induced Alzheimer's disease (AD) mouse model.MethodsTwenty four TLR4 gene knockout mice (TLR4KO, male, body weight: 25–30g) and 24 wild type mice (WT, male, body weight: 25–30g) were randomly assigned into 4 groups: Normal saline control (WT.NS, wild type mice were injected 1ul normal saline into bilateral hippocampus), AD model group (WT. Aβ, wild type mice were injected with 1ul Aβ1–42 (5ug/ul) into bilateral hippocampus), TLR4KO‐normal saline control (TLR4KO.NS, TLR4KO mice were injected with 1ul normal saline into bilateral hippocampus), and TLR4KO Aβ group (TLR4KO.Aβ, TLR4KO mice were injected with 1ul Aβ1–42 (5ug/ul) into bilateral hippocampus). Seven days after injection, the learning and memorial functions were tested using Morris Water Maze (MWM). The repeated measures analysis of variance was used to analyze navigation test, the one‐way ANOVA and LSD post‐hoc comparisons were used for probe trial analyses. HE staining was performed.; and the expression of Bcl‐2 and Caspase‐3 was assayed by Western blot, the results was analyzed by one‐way ANOVA.Results1. Compared with normal saline control groups(WT.NS), the AD groups (WT. Aβ) showed a longer escape latency (P&lt;0.05), increased percentage of time in outer annulus (P&lt;0.05) in the place navigation test, reduced percentage of time in the platform quadrant and decreasing times of traversing platform (P&lt;0.05) in the spatial probe test. Compared with AD model groups(WT.Aβ), the escape latency and the percentage of time in outer annulus were decreased in TLR4KOAβ groups (P&lt;0.05), and the percentage of time in the platform quadrant and the times of traversing platform were increased (P&lt;0.05). There was no significant difference of swimming speed amonge each group (P&gt;0.05). 2. Hematoxylin eosin staining showed that compared with normal saline control groups, the neurons in AD groups distribute loosely and irregularly, and more dead neurons were observed. TLR4KOAβ groups showed a attenuated damage in hippocamus compared with the AD groups. 3. The results of western blots suggested that compared with control groups, the expression of Bcl‐2 in AD groups were significant reduced (P&lt;0.05) and the expression of Caspase‐3 were increased (P&lt;0.05); the expression of Bcl‐2 in the TLR4KO Aβ groups were increased (P&lt;0.05) and the level of Caspase‐3 was reduced (P&lt;0.05) when compared with AD groups.Conclusion1. Injection of 5ug Aβ1–42 into bilateral hippocampus can obvious impaire the learning and memorial functions and induced histological damage in hippocampus of mice, which provides an effective method for establishing mouse model of AD; 2. TLR4 knockout can attenuate cognitive impairment and tissue damage induced by hippocampal injection of Aβ1–42 in the AD model, which may be partly achieved by reducing apoptosis.Support or Funding InformationThis work was supported by China National Nature Scientific Foundation (81571469 and 81271268)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Protection against β-amyloid neurotoxicity by a non-toxic endogenous N-terminal β-amyloid fragment and its active hexapeptide core sequence.

High levels (μM) of beta amyloid (Aβ) oligomers are known to trigger neurotoxic effects, leading to synaptic impairment, behavioral deficits, and apoptotic cell death. The hydrophobic C-terminal domain of Aβ, together with sequences critical for oligomer formation, is essential for this neurotoxicity. However, Aβ at low levels (pM-nM) has been shown to function as a positive neuromodulator and this activity resides in the hydrophilic N-terminal domain of Aβ. An N-terminal Aβ fragment (1-15/16), found in cerebrospinal fluid, was also shown to be a highly active neuromodulator and to reverse Aβ-induced impairments of long-term potentiation. Here, we show the impact of this N-terminal Aβ fragment and a shorter hexapeptide core sequence in the Aβ fragment (Aβcore: 10-15) to protect or reverse Aβ-induced neuronal toxicity, fear memory deficits and apoptotic death. The neuroprotective effects of the N-terminal Aβ fragment and Aβcore on Aβ-induced changes in mitochondrial function, oxidative stress, and apoptotic neuronal death were demonstrated via mitochondrial membrane potential, live reactive oxygen species, DNA fragmentation and cell survival assays using a model neuroblastoma cell line (differentiated NG108-15) and mouse hippocampal neuron cultures. The protective action of the N-terminal Aβ fragment and Aβcore against spatial memory processing deficits in amyloid precursor protein/PSEN1 (5XFAD) mice was demonstrated in contextual fear conditioning. Stabilized derivatives of the N-terminal Aβcore were also shown to be fully protective against Aβ-triggered oxidative stress. Together, these findings indicate an endogenous neuroprotective role forthe N-terminal Aβ fragment, while active stabilized N-terminal Aβcore derivatives offer the potential for therapeutic application.

Нейродегенеративные изменения, вызванные введением фрагмента (25–35) β-амилоидного пептида в гиппокамп, связаны с активацией NGF-сигналинга

Нейродегенеративные изменения, вызванные введением фрагмента (25–35) β-амилоидного пептида в гиппокамп, связаны с активацией NGF-сигналинга

Antiamnesic effects divaza and its component model β-amyloid amnesia

On amnesia models induced by (icv) injection of β-amyloid fragment 25-35 peptide were evaluated antiamnestic actitity. It was used of active antibody preparations (RA AT) to protein S100 (tenoten), to eNOS (impaza) and combinations (divaza) antiamnestic activity behavioral tests novel object conditioned response passive avoidance. Under the influence of RA AT S100 observed recovery of violation of the β-amyloid short-term memory (1 hour after the initial presentation of objects), and RA AT eNOS were more effective when tested 24 hours later. Combined medication completely compensate for the simulated deflection behavior of rats did not differ from the intact control. The CRPA RA AT S100 had the greatest impact on the LP entry into the dark compartment, and RA AT eNOS influenced primarily on the emotional component of the reaction. When using the integrated product tends to increase the LP entry into the dark compartment was observed in the absence of changes in the number of boluses. Thus, tenoten had the greatest impact on cognitive impairment, impaza greater effect on the symptoms associated with surgery. Combined preparation divaza rendered more effective action, leveling and amnesia neophobia, which confirms the need for further research and prospect release of active drugs in models of neurodegenerative disorders.

Regulation of presynaptic Ca2+, synaptic plasticity and contextual fear conditioning by a N-terminal β-amyloid fragment.

Soluble β-amyloid has been shown to regulate presynaptic Ca(2+) and synaptic plasticity. In particular, picomolar β-amyloid was found to have an agonist-like action on presynaptic nicotinic receptors and to augment long-term potentiation (LTP) in a manner dependent upon nicotinic receptors. Here, we report that a functional N-terminal domain exists within β-amyloid for its agonist-like activity. This sequence corresponds to a N-terminal fragment generated by the combined action of α- and β-secretases, and resident carboxypeptidase. The N-terminal β-amyloid fragment is present in the brains and CSF of healthy adults as well as in Alzheimer's patients. Unlike full-length β-amyloid, the N-terminal β-amyloid fragment is monomeric and nontoxic. In Ca(2+) imaging studies using a model reconstituted rodent neuroblastoma cell line and isolated mouse nerve terminals, the N-terminal β-amyloid fragment proved to be highly potent and more effective than full-length β-amyloid in its agonist-like action on nicotinic receptors. In addition, the N-terminal β-amyloid fragment augmented theta burst-induced post-tetanic potentiation and LTP in mouse hippocampal slices. The N-terminal fragment also rescued LTP inhibited by elevated levels of full-length β-amyloid. Contextual fear conditioning was also strongly augmented following bilateral injection of N-terminal β-amyloid fragment into the dorsal hippocampi of intact mice. The fragment-induced augmentation of fear conditioning was attenuated by coadministration of nicotinic antagonist. The activity of the N-terminal β-amyloid fragment appears to reside largely in a sequence surrounding a putative metal binding site, YEVHHQ. These findings suggest that the N-terminal β-amyloid fragment may serve as a potent and effective endogenous neuromodulator.

Protective action of glutamate antibodies on increased expression of genes of programmed death of rat brain cells induced by injection of a β-amyloid fragment (25–35)

Glutamate antibodies intranasally administered to Wistar rats at a dose of 300 μg/kg reduced the elevated levels of expression of Aifml, Casp3, and Parp 1 genes in the prefrontal cortex and Aifml and Casp3 genes in the hippocampus on the third day after administration of the β-amyloid fragment Aβ25-35 into the Meynert nuclei of the brain. Changes in Aifm1, Bax, Casp3, and Parp 1 gene expression were not found in the hypothalamus, and changes in Bax gene expression were not found in the brain structures studied. The discovered features of gene expression in the prefrontal cortex and hippocampus are considered in terms of development of various cell-death programs, which are modulated by glutamate antibodies.

P.5.a.006 The effect of intracerebroventricular administration of (25–35)-β-amyloid fragment on EEG and cognition in the rat – a pilot study

P.5.a.006 The effect of intracerebroventricular administration of (25–35)-β-amyloid fragment on EEG and cognition in the rat – a pilot study

P.5.e.001 The influence of aggregated (25–35)-β-amyloid fragment on cell proliferation and microglial activation in the rat hippocampus

P.5.e.001 The influence of aggregated (25–35)-β-amyloid fragment on cell proliferation and microglial activation in the rat hippocampus

Structure and membrane interactions of the β-amyloid fragment 25–35 as viewed using spectroscopic approaches

The β-amyloid fragment peptide 25-35 (Aβ(25-35)) is recognized as the cytotoxic sequence of the parent peptide Aβ. However, it remains unclear whether its neurotoxicity originates from its fibrillar form, how it interacts with lipid membranes, and whether cholesterol modulates these interactions. These questions have been addressed at a molecular level using various microscopic and spectroscopic techniques. The data show that Aβ(25-35) forms protofilaments at pH 7.4 at a concentration of 5 mM in the absence and presence of DMPC/DMPG model membranes. The peptide adopts a predominant aggregated β-sheet conformation under these conditions. However, as the peptide concentration decreases, the β-sheet structure tends to disappear for the benefit of β-turns, suggesting that the peptide association is reversible. The β-sheet structure formed by Aβ(25-35) appears to be atypical and characterized by the absence of intermolecular dipolar coupling and by a parallel strand configuration. The data show that Aβ(25-35)-phospholipid interactions are characterized by an increase in the conformational order of the lipid acyl chains and a change in the fluidity/elasticity of the bilayers. Concomitantly, the peptide seems to lose a few β-sheet structures, which suggests that the interactions between Aβ(25-35) and DMPC/DMPG membranes are partly driven by peptide concentration. Interactions indeed seem to occur when part of the peptides is not involved in protofilaments and increase as the proportion of the free peptide species increases. The interactions are very similar in the presence of cholesterol, except that the concentration effect of Aβ(25-35) is cancelled, suggesting that Chol limits the penetration of the peptide inside the bilayers.

Deletion of microsomal prostaglandin E synthase-1 protects neuronal cells from cytotoxic effects of β-amyloid peptide fragment 31–35

Epidemiological studies have suggested that the long-term use of nonsteroidal anti-inflammatory drugs that inhibit cyclooxygenase (COX) activity moderates the onset or progression of Alzheimer’s disease (AD). Thus it has been suggested that prostaglandin E2 (PGE2), a major end-product of COX, may play a pathogenic role in AD, but the involvement of PGE synthase (PGES), a terminal enzyme downstream from COX, has not been fully elucidated. To examine the involvement in AD pathology of microsomal PGES-1 (mPGES-1), a PGES enzyme, we here prepared primary cerebral neuronal cells from the cerebri of wild-type and mPGES-1-deficient mice and then treated them with β-amyloid (Aβ) fragment 31–35 (Aβ31–35), which represents the shortest sequence of native Aβ peptide required for neurotoxicity. Treatment of wild-type neuronal cells with Aβ31–35 induced mPGES-1 gene expression and PGE2 production, followed by significant apoptotic cell death, but apoptosis was not induced in mPGES-1-deficient cells. Furthermore, the combined treatment of Aβ31–35 and PGE2 induced apoptosis in mPGES-1-deficient neuronal cells. These results indicated that mPGES-1 is induced during Aβ-mediated neuronal cell death and is involved in Aβ-induced neurotoxicity associated with AD pathology.

Effect of β‐amyloid (25–35) on mitochondrial function and expression of mitochondrial permeability transition pore proteins in rat hippocampal neurons

The aim of this study was to assess the effect of the β-amyloid fragment Aβ(25-35) on mitochondrial structure and function and on the expression of proteins associated with the mitochondrial permeability transition pore (MPTP) in rat hippocampal neurons. Ninety clean-grade Sprague-Dawley rats were randomly assigned to six groups (n = 15 per group). Aβ(25-35) (1, 5, or 10 µg/rat) was injected into hippocampal area CA1. Normal saline was injected as a control. The effect of Aβ(25-35) injection on hippocampal structure was assessed by transmission electron microscopy. Ca(2+) -ATPase activity, [Ca(2+) ](i) , and mitochondrial membrane potential were measured. The expression of genes associated with the MPTP, including the voltage-dependent anion channel (VDAC), adenine nucleotide translocator (ANT), and cyclophilin D (Cyp-D), were evaluated. Results showed that Aβ(25-35) injection damaged the mitochondrial structure of hippocampal neurons, decreased Ca(2+) -ATPase activity and mitochondrial membrane potential, and increased [Ca(2+) ](i) . The expression levels for VDAC, ANT, and Cyp-D in all groups were significantly (P < 0.05) higher than those in the normal control group after Aβ(25-35) injection. These results indicate that Aβ(25-35) damages mitochondria in rat hippocampal neurons and effects mitochondrial dysfunction, as well as increasing the expression of genes associated with the MPTP. Mitochondrial dysfunction may result in increased MPTP gene expression, leading to neurodegenerative effects.

Behavior of β-Amyloid 1−16 at the Air−Water Interface at Varying pH by Nonlinear Spectroscopy and Molecular Dynamics Simulations

The adsorption and aggregation of β-amyloid (1-16) fragment at the air-water interface was investigated by the combination of second harmonic generation (SHG) spectroscopy, Brewster angle microscopy (BAM), and molecular dynamics simulations (MD). The Gibbs free energy of surface adsorption was measured to be -10.3 kcal/mol for bulk pHs of 7.4 and 3, but no adsorption was observed for pH 10-11. The 1-16 fragment is believed not to be involved in fibril formation of the β-amyloid protein, but it exhibits interesting behavior at the air-water interface, as manifested in two time scales for the observed SHG response. The shorter time scale (minutes) reflects the surface adsorption, and the longer time scale (hours) reflects rearrangement and aggregation of the peptide at the air-water interface. Both of these processes are also evidenced by BAM measurements. MD simulations confirm the pH dependence of surface behavior of the β-amyloid, with largest surface affinity found at pH = 7. It also follows from the simulations that phenylalanine is the most surface exposed residue, followed by tyrosine and histidine in their neutral form.

Effect of flavonoids on the Aβ(25-35)-phospholipid bilayers interaction

Amyloid-β peptide (Aβ) is the major component of amyloid deposits found in the brain tissue of Alzheimer patients. The tendency of amyloid peptide to form amyloid plaques is known to be related to the features of the plasma membrane. Flavonoids, a group of naturally occurring molecules, exert beneficial properties to human health thanks to their antioxidant property; this property depends on their capacity to interact and permeate the cell membrane lipid bilayer. In the present research we report an Electron Paramagnetic Resonance (EPR) investigation of 2-dioleoyl- sn-glycero-3-phosphocholine (DOPC) membranes interacting with the β-amyloid fragment Aβ(25-35), in the presence of flavonoids rutin, quercetin, naringin and naringenin. Our results, evidencing a flavonoid-dependent rigidifying effect of the bilayer, may provide the molecular basis to explain the known neuroprotective effect of flavonoid compounds.

Membrane charge dependent states of the β-amyloid fragment Aβ (16–35) with differently charged micelle aggregates

A β (16–35) is the hydrophobic central core of β-amyloid peptide, the main component of plaques found in the brain tissue of Alzheimer's disease patients. Depending on the conditions present, β-amyloid peptides undergo a conformational transition from random coil or α-helical monomers, to highly toxic β-sheet oligomers and aggregate fibrils. The behavior of β-amyloid peptide at plasma membrane level has been extensively investigated, and membrane charge has been proved to be a key factor modulating its conformational properties. In the present work we probed the conformational behavior of A β (16–35) in response to negative charge modifications of the micelle surface. CD and NMR conformational analyses were performed in negatively charged pure SDS micelles and in zwitterionic DPC micelles “doped” with small amounts of SDS. To analyze the tendency of A β (16–35) to interact with these micellar systems, we performed EPR experiments on three spin-labeled analogues of A β (16–35), bearing the methyl 3-(2,2,5,5-tetramethyl-1-oxypyrrolinyl) methanethiolsulfonate spin label at the N-terminus, in the middle of the sequence and at the C-terminus, respectively. Our conformational data show that, by varying the negative charge of the membrane, A β (16–35) undergoes a conformational transition from a soluble helical–kink–helical structure, to a U-turn shaped conformation that resembles protofibril models.