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PubMed2005

Milk amyloid A: correlation with cellular indices of mammary inflammation in cows with normal and raised serum amyloid A.

This study compared concentrations of amyloid A in bovine milk with the cell-based indicators of intramammary inflammation, somatic cell count and California Mastitis Test. Mammary quarter data pertaining to 180 cows were categorised according to concentrations of serum amyloid A in the cow of origin. Ranked correlation, ranked regression and receiver operator characteristics all demonstrated acceptable agreement between milk amyloid A concentrations and cell-based indices. There were some indications of reduction in this agreement, in cows with raised concentrations of serum amyloid A. However, there were also indications that serum amyloid A did not significantly influence milk amyloid A. The results of the current study indicate that milk amyloid A exhibits good correlation with established cell-based indicators of intramammary inflammation.

Animals↗
PubMed2000

Amyloid fibril formation by A beta 16-22, a seven-residue fragment of the Alzheimer's beta-amyloid peptide, and structural characterization by solid state NMR.

The seven-residue peptide N-acetyl-Lys-Leu-Val-Phe-Phe-Ala-Glu-NH(2), called A beta(16-22) and representing residues 16-22 of the full-length beta-amyloid peptide associated with Alzheimer's disease, is shown by electron microscopy to form highly ordered fibrils upon incubation of aqueous solutions. X-ray powder diffraction and optical birefringence measurements confirm that these are amyloid fibrils. The peptide conformation and supramolecular organization in A beta(16-22) fibrils are investigated by solid state (13)C NMR measurements. Two-dimensional magic-angle spinning (2D MAS) exchange and constant-time double-quantum-filtered dipolar recoupling (CTDQFD) measurements indicate a beta-strand conformation of the peptide backbone at the central phenylalanine. One-dimensional and two-dimensional spectra of selectively and uniformly labeled samples exhibit (13)C NMR line widths of <2 ppm, demonstrating that the peptide, including amino acid side chains, has a well-ordered conformation in the fibrils. Two-dimensional (13)C-(13)C chemical shift correlation spectroscopy permits a nearly complete assignment of backbone and side chain (13)C NMR signals and indicates that the beta-strand conformation extends across the entire hydrophobic segment from Leu17 through Ala21. (13)C multiple-quantum (MQ) NMR and (13)C/(15)N rotational echo double-resonance (REDOR) measurements indicate an antiparallel organization of beta-sheets in the A beta(16-22) fibrils. These results suggest that the degree of structural order at the molecular level in amyloid fibrils can approach that in peptide or protein crystals, suggest how the supramolecular organization of beta-sheets in amyloid fibrils can be dependent on the peptide sequence, and illustrate the utility of solid state NMR measurements as probes of the molecular structure of amyloid fibrils. A beta(16-22) is among the shortest fibril-forming fragments of full-length beta-amyloid reported to date, and hence serves as a useful model system for physical studies of amyloid fibril formation.

Amyloid beta-Peptides↗
PubMed1997

Amino-terminal identity of co-existent amyloid and non-amyloid immunoglobulin kappa light chain deposits. A human disease to study alterations of protein conformation.

Tissue deposition of monoclonal immunoglobulin light chains is a serious complication in some patients with B cell proliferative disorders. The deposits are typically fibrillar and Congophilic in amyloid (AL) and non-fibrillar and Congophobic in light chain deposition disease (LCDD), and rarely coexist in the same patient. From post-mortem tissue of an individual with fibrillar and non-fibrillar kappa light chain deposits in different sites, we separately extracted and analysed biochemically and immunochemically the non-amyloid deposits from isolated glomeruli, the amyloid from isolated renal arteries and the amyloid from myocardium in which the only deposits were amyloid restricted to mural arteries. Western blotting analysis of both the extracted amyloid and the non-amyloid deposits demonstrated 25-kD bands immunoreactive with anti-kappa antibody, and the identity of the N-terminal amino acid sequences that belong to the variable region kappaIV light chain subgroup. This is the first human disease in which antigenically similar but morphologically different deposits have been separately biochemically analysed. We propose that combined LCDD and AL is an ideal human disease to study the relationships and the factors that influence the conversion of non-amyloidogenic to amyloidogenic conformations.

Aged↗
PubMed2001

An amyloid-forming peptide from the yeast prion Sup35 reveals a dehydrated beta-sheet structure for amyloid.

X-ray diffraction and other biophysical tools reveal features of the atomic structure of an amyloid-like crystal. Sup35, a prion-like protein in yeast, forms fibrillar amyloid assemblies intrinsic to its prion function. We have identified a polar peptide from the N-terminal prion-determining domain of Sup35 that exhibits the amyloid properties of full-length Sup35, including cooperative kinetics of aggregation, fibril formation, binding of the dye Congo red, and the characteristic cross-beta x-ray diffraction pattern. Microcrystals of this peptide also share the principal properties of the fibrillar amyloid, including a highly stable, beta-sheet-rich structure and the binding of Congo red. The x-ray powder pattern of the microcrystals, extending to 0.9-A resolution, yields the unit cell dimensions of the well-ordered structure. These dimensions restrict possible atomic models of this amyloid-like structure and demonstrate that it forms packed, parallel-stranded beta-sheets. The unusually high density of the crystals shows that the packed beta-sheets are dehydrated, despite the polar character of the side chains. These results suggest that amyloid is a highly intermolecularly bonded, dehydrated array of densely packed beta-sheets. This dry beta-sheet could form as Sup35 partially unfolds to expose the peptide, permitting it to hydrogen-bond to the same peptide of other Sup35 molecules. The implication is that amyloid-forming units may be short segments of proteins, exposed for interactions by partial unfolding.

Amino Acid Sequence↗
PubMed2005

Chemical typing of porcine systemic amyloid as AA-amyloid.

Systemic AA amyloidosis is frequently reported in a wide variety of domestic and wild animal species. Porcine amyloidosis is rare and the amyloid has not been typed chemically thus far. In the present study, we have extracted porcine amyloid from formalin-fixed tissue sections. By subsequent amino acid sequencing, an N-terminal fragment was obtained identifying porcine systemic amyloid as AA amyloid. The N-terminal sequence had a great homology to bovine and ovine SAA1, suggesting that pig AA amyloid is derived from the systemic isoform of SAA. It is argued that the low incidence of amyloidosis in pigs is not likely to be attributed to unique features of porcine amyloid precursor protein. Elucidation of the basis for the high apparent resistance of pigs against amyloidosis may yield important clues for treatment and prevention of amyloidosis in other species. This is the first report on chemical identification of porcine amyloid.

Amino Acid Sequence↗
PubMed1969

Immunologic studies of water-soluble human amyloid fibrils. Comparative studies of eight amyloid preparations.

Eight preparations of soluble amyloid and degraded amyloid (DAM) were compared immunologically. Unlike amyloid fibrils, six of eight preparations of DAM proved to be relatively strong immunogens. Antisera to DAM reacted weakly or not at all with normal human serum or extracts of normal tissues, but were specifically reactive with amyloid fibrils or DAM. Comparative studies of DAM'S from eight different subjects showed some degree of cross-reactivity among them, yet demonstrated that they were not identical. Similar conclusions were obtained by quantitative precipitin and complement fixation analyses. Comparison of the amyloid fibrils with the homologous DAM by complement fixation and absorption studies demonstrated the existence in DAM of antigenic determinants that were lacking or inaccessible in the native fibrils. A search for amyloid precursors and antibodies to amyloid in the sera of 12 patients proved unsuccessful.

Amyloid↗
PubMed1998

Progressive cardiac amyloidosis following liver transplantation for familial amyloid polyneuropathy: implications for amyloid fibrillogenesis.

BACKGROUND: Circulating transthyretin (TTR) is derived from the liver, and orthotopic liver transplantation (OLT) is widely performed for variant TTR-associated familial amyloid polyneuropathy (FAP). The effect of OLT on FAP-related cardiac amyloid is of particular interest because wild-type TTR can itself be deposited as senile cardiac amyloid. METHODS: Serial echocardiography was performed in 20 FAP patients, 14 of whom underwent OLT, and 10 other liver transplant patients. Follow-up included serum amyloid P component scintigraphy and measurement of plasma TTR before and after OLT. RESULTS: Cardiac amyloidosis progressed rapidly in three FAP patients (TTR Pro52 and Thr84 mutations) after OLT, even though the deposits elsewhere had stabilized or regressed. Results of echocardiography improved in three transplant patients with TTR Met30 and remained normal in seven other patients. Plasma TTR levels were altered substantially after OLT, but they did not reflect the cardiac findings. CONCLUSIONS: Although amyloid deposition in FAP is generally inhibited after OLT, cardiac amyloidosis can be exacerbated, probably due to enhanced deposition of wild-type TTR on a template of amyloid derived from variant TTR. The phenomenon may be mutation-dependent. These findings suggest that amyloid formation de novo and its subsequent accumulation can be promoted by different factors, which may be organ-specific.

Amyloid Neuropathies↗
PubMed2006

Impaired NH2-terminal processing of human proislet amyloid polypeptide by the prohormone convertase PC2 leads to amyloid formation and cell death.

Islet amyloid, formed by aggregation of islet amyloid polypeptide (IAPP; amylin), is a pathological characteristic of the pancreas in type 2 diabetes and may contribute to the progressive loss of beta-cells in this disease. We tested the hypothesis that impaired processing of the IAPP precursor proIAPP contributes to amyloid formation and cell death. GH3 cells lacking the prohormone convertase 1/3 (PC1/3) and IAPP and with very low levels of prohormone convertase 2 (PC2) were transduced with adenovirus (Ad) expressing human or rat (control) proIAPP linked to green fluorescent protein, with or without Ad-PC2 or Ad-PC1/3. Expression of human proIAPP increased the number of transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells 96 h after transduction (+hIAPP 8.7 +/- 0.4% vs. control 3.0 +/- 0.4%; P < 0.05). COOH-terminal processing of human proIAPP by PC1/3 increased (hIAPP+PC1/3 10.4 +/- 0.7%; P < 0.05), whereas NH(2)-terminal processing of proIAPP by addition of PC2 markedly decreased (hIAPP+PC2 5.5 +/- 0.5%; P < 0.05) the number of apoptotic GH3 cells. Islets from mice lacking PC2 and with beta-cell expression of human proIAPP (hIAPP(+/+)/PC2(-/-)) developed amyloid associated with beta-cell death during 2-week culture. Rescue of PC2 expression by ex vivo transduction with Ad-PC2 restored NH(2)-terminal processing to mature IAPP and decreased both the extent of amyloid formation and the number of TUNEL-positive cells (-PC2 26.5 +/- 4.1% vs. +PC2 16.1 +/- 4.3%; P < 0.05). These findings suggest that impaired NH(2)-terminal processing of proIAPP leads to amyloid formation and cell death and that accumulation of the NH(2)-terminally extended human proIAPP intermediate may be a critical initiating step in amyloid formation.

Adenoviridae↗
PubMed1990

Generation and use of site-specific antibodies to serum amyloid A for probing amyloid A development.

Serum amyloid A (SAA) is an acute phase reactant and the putative precursor of an amyloid fibril protein (AA). During amyloidogenesis in mice, the C-terminal portion of SAA that consists of 28 amino acids is cleaved off to produce the 75 amino acid AA. Of three known isotypes of SAA, SAA2 has been identified as amyloidogenic. For differential immunologic recognition of SAA and AA, antisera were generated in rabbits against AA protein and a synthetic peptide corresponding to the C-terminal (amino acids 84 to 103) of murine SAA2. The anti-AA antiserum reacted with AA and SAA, but the anti-peptide antiserum reacted with SAA only. Immunohistochemically anti-peptide antiserum predominantly stained the rims of murine amyloid deposits. In contrast, anti-AA antiserum generated an overall homogeneous staining of amyloid deposits. The data lend support to a view that SAA are concentrated in the vicinity of the surrounding cells (mostly macrophages) where they are processed to AA, or that SAA are deposited initially as components of the amyloid fibrils onto the outside margin of amyloid deposits and the C-terminus is cleaved off as maturation of the amyloid fibril progresses.

Animals↗
PubMed1987

Enhancement of amyloid induction by amyloid fibril fragments in hamster.

An extract (fibril amyloid-enhancing factor) prepared by sonication of a suspension of water-purified hamster AA-amyloid fibrils showed an amyloid-enhancing effect upon intraperitoneal injection into hamsters. The fibril amyloid-enhancing factor was identical to the original fibrils according to the results of infrared spectroscopy, gel filtration, gel electrophoresis, and Western blotting; although lyophilized samples of the extract did not show any green birefringence after staining with Congo red. From these results, it was concluded that fibril amyloid-enhancing factor represents small fragments of amyloid fibrils which enhance in vivo formation of amyloid fibrils.

Amyloid↗
PubMed1985

The amyloid in familial amyloid cardiomyopathy of Danish origin is related to pre-albumin.

Amyloid obtained from the myocardium of a patient (Han) with familial amyloid cardiomyopathy of Danish origin was studied. Gel filtration and electrophoresis of purified and denatured amyloid fibrils Han revealed various fractions ranging in mol. wt from 40,000 to 8,000 daltons. Amyloid Han and fractions reacted with an antiserum against amyloid Han showing a reaction of identity with each other; partial identity between Han and human pre-albumin was observed, while no reaction was seen with AA or AL proteins. Cardiac tissue sections from Han showed reactivity with antisera to amyloid Han, pre-albumin and protein AP, but not with anti-AA or anti-AL in indirect immunofluorescence. Amino acid composition and sequence studies of a protein fraction of amyloid Han with mol. wt 15,000 daltons confirmed the structural relationship with pre-albumin.

Adult↗
PubMed1984

Lack of evidence for protein AA reactivity in amyloid deposits of lattice corneal dystrophy and amyloid corneal degeneration.

Amyloid fibrils occurring in primary and myeloma-associated (AL), secondary (AA), and certain neuropathic hereditary forms of systemic amyloidosis can be distinguished biochemically or immunohistologically as being composed of immunoglobulin light chain, protein AA, or prealbumin respectively. All types of systemic and several localized forms of amyloidosis contain amyloid P component (protein AP). We studied formalin-fixed tissue from eight cases of lattice corneal dystrophy by the immunoperoxidase method using antisera to proteins AA and AP, to normal serum prealbumin and prealbumin isolated from a case of hereditary amyloidosis, and to light-chain determinants; additional cases were examined by indirect immunofluorescence of fresh-frozen material. We found weak (1:10 dilution) staining with anti-AP, but no reactivity with other antisera. Congo red staining was resistant to pretreatment of sections with potassium permanganate, a characteristic of non-AA amyloid. Two-dimensional gels of solubilized proteins from frozen tissue from two cases of lattice corneal dystrophy resembled those obtained from normal human cornea. Western blots of two cases of polymorphous amyloid degeneration and solubilized protein from normal cornea did not react with radioactive iodine-labeled anti-AA or anti-AP with purified protein AP and unfixed protein AA amyloid tissue as controls. We were unable to corroborate the presence of protein AA in the amyloid deposits of lattice corneal dystrophy. Although staining with antiserum to protein AP was demonstrable, the molecular configuration of this protein in stromal deposits remains to be defined.

Amyloid↗
PubMed2005

Cerebral microvascular amyloid beta protein deposition induces vascular degeneration and neuroinflammation in transgenic mice expressing human vasculotropic mutant amyloid beta precursor protein.

Cerebral vascular amyloid beta-protein (Abeta) deposition, also known as cerebral amyloid angiopathy, is a common pathological feature of Alzheimer's disease. Additionally, several familial forms of cerebral amyloid angiopathy exist including the Dutch (E22Q) and Iowa (D23N) mutations of Abeta. Increasing evidence has associated cerebral microvascular amyloid deposition with neuroinflammation and dementia in these disorders. We recently established a transgenic mouse model (Tg-SwDI) that expresses human vasculotropic Dutch/Iowa mutant amyloid beta-protein precursor in brain. Tg-SwDI mice were shown to develop early-onset deposition of Abeta exhibiting high association with cerebral microvessels. Here we present quantitative temporal analysis showing robust and progressive accumulation of cerebral microvascular fibrillar Abeta accompanied by decreased cerebral vascular densities, the presence of apoptotic cerebral vascular cells, and cerebral vascular cell loss in Tg-SwDI mice. Abundant neuroinflammatory reactive astrocytes and activated microglia strongly associated with the cerebral microvascular fibrillar Abeta deposits. In addition, Tg-SwDI mouse brain exhibited elevated levels of the inflammatory cytokines interleukin-1beta and -6. Together, these studies identify the Tg-SwDI mouse as a unique model to investigate selective accumulation of cerebral microvascular amyloid and the associated neuroinflammation.

Amyloid beta-Peptides↗
PubMed1999

Elimination of the class A scavenger receptor does not affect amyloid plaque formation or neurodegeneration in transgenic mice expressing human amyloid protein precursors.

The class A scavenger receptor (SR) is expressed on reactive microglia surrounding cerebral amyloid plaques in Alzheimer's disease (AD). Interactions between the SR and amyloid beta peptides (Abeta) in microglial cultures elicit phagocytosis of Abeta aggregates and release of neurotoxins. To assess the role of the SR in amyloid clearance and Abeta-associated neurodegeneration in vivo, we used the platelet-derived growth factor promoter to express human amyloid protein precursors (hAPPs) in neurons of transgenic mice. With increasing age, hAPP mice develop AD-like amyloid plaques. We bred heterozygous hAPP (hAPP(+/-)) mice that were wild type for SR (SR(+/+)) with SR knockout (SR(-/-)) mice. Crosses among the resulting hAPP(+/-)SR(+/-) offspring yielded hAPP(+/-) and hAPP(-/-) littermates that were SR(+/+) or SR(-/-). These second-generation mice were analyzed at 6 and 12 months of age for extent of cerebral amyloid deposition and loss of synaptophysin-immunoreactive presynaptic terminals. hAPP(-/-)SR(-/-) mice showed no lack of SR expression, plaque formation, or synaptic degeneration, indicating that lack of SR expression does not result in significant accumulation of endogenous amyloidogenic or neurotoxic factors. In hAPP(+/-) mice, ablation of SR expression did not alter number, extent, distribution, or age-dependent accumulation of plaques; nor did it affect synaptic degeneration. Our results do not support a critical pathogenic role for microglial SR expression in neurodegenerative alterations associated with cerebral beta amyloidosis.

Alzheimer Disease↗
PubMed2003

Diffuse amyloid deposition, but not plaque number, is reduced in amyloid precursor protein/presenilin 1 double-transgenic mice by pathway lesions.

Alzheimer's disease (AD) is the most common form of dementia in the elderly, and the characteristic pathological hallmarks of the disease are neuritic plaques and neurofibrillary tangles. The sequence of events leading to the extracellular deposition of amyloidbeta (Abeta) peptides in plaques or in diffuse deposits is not clear. Here we investigate the relation between disrupted axonal transport of amyloid precursor protein (APP) and/or Abeta and the deposition of Abeta in the deafferented terminal fields in APP/presenilin 1 double-transgenic AD-model mice. In the first experiment we ablated entorhinal cortex neurons and examined the subsequent changes in amyloid deposition in the hippocampus 1 month later. We show that there is a substantial reduction in the amount of diffuse amyloid deposits in the denervated areas of the hippocampus. Further, to investigate the effects of long-term deafferentation, in a second experiment we cut the fimbria-fornix and analyzed the brains 11 months post-lesion. Diffuse amyloid deposits in the deafferented terminal fields of area CA1 and subiculum were dramatically reduced as assessed by image analysis of the Abeta load. Our findings indicate that neuronal ablations decrease diffuse amyloid deposits in the terminal fields of these neurons, and, further, that pathway lesions similarly decrease the amount of diffuse amyloid deposits in the terminal fields of the lesioned axons. Together, this suggests that the axonal transport of APP and/or Abeta and subsequent secretion of Abeta at terminals plays an important role in the deposition of Abeta protein in Alzheimer's disease, and, further, that diffuse deposits do not develop into plaques.py>

Alzheimer Disease↗
PubMed2005

The familial dementia BRI2 gene binds the Alzheimer gene amyloid-beta precursor protein and inhibits amyloid-beta production.

Alzheimer disease (AD), the most common senile dementia, is characterized by amyloid plaques, vascular amyloid, neurofibrillary tangles, and progressive neurodegeneration. Amyloid is mainly composed by amyloid-beta (A(beta)) peptides, which are derive from processing of the beta-amyloid precursor protein (APP), better named amyloid-beta precursor protein (A(beta)PP), by secretases. The A(beta)PP intracellular domain (AID), which is released together with A(beta), has signaling function, since it modulates apoptosis and transcription. Despite its biological and pathological importance, the mechanisms regulating A(beta)PP processing are poorly understood. As cleavage of other gamma-secretase substrates is regulated by membrane bound proteins, we have postulated the existence of integral membrane proteins that bind A(beta)PP and regulate its processing. Here, we show that BRI2, a type II membrane protein, interacts with A(beta)PP. Interestingly, 17 amino acids corresponding to the NH2-terminal portion of A(beta) are necessary for this interaction. Moreover, BRI2 expression regulates A(beta)PP processing resulting in reduced A(beta) and AID levels. Altogether, these findings characterize the BRI2-A(beta)PP interaction as a regulatory mechanism of A(beta)PP processing that inhibits A(beta) production. Notably, BRI2 mutations cause familial British (FBD) and Danish dementias (FDD) that are clinically and pathologically similar to AD. Finding that BRI2 pathogenic mutations alter the regulatory function of BRI2 on A(beta)PP processing would define dysregulation of A(beta)PP cleavage as a pathogenic mechanism common to AD, FDD, and FBD.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Reducing cerebral microvascular amyloid-beta protein deposition diminishes regional neuroinflammation in vasculotropic mutant amyloid precursor protein transgenic mice.

Cerebral microvascular amyloid-beta (Abeta) protein deposition is emerging as an important contributory factor to neuroinflammation and dementia in Alzheimer's disease and related familial cerebral amyloid angiopathy disorders. In particular, cerebral microvascular amyloid deposition, but not parenchymal amyloid, is more often correlated with dementia. Recently, we generated transgenic mice (Tg-SwDI) expressing the vasculotropic Dutch (E693Q)/Iowa (D694N) mutant human Abeta precursor protein in brain that accumulate abundant cerebral microvascular fibrillar amyloid deposits. In the present study, our aim was to assess how the presence or absence of fibrillar Abeta deposition in the cerebral microvasculature affects neuroinflammation in Tg-SwDI mice. Using Tg-SwDI mice bred onto an apolipoprotein E gene knock-out background, we found a strong reduction of fibrillar cerebral microvascular Abeta deposition, which was accompanied by a sharp decrease in microvascular-associated neuroinflammatory cells and interleukin-1beta levels. Quantitative immunochemical measurements showed that this reduction of the neuroinflammation occurred in the absence of lowering the levels of total Abeta40/Abeta42 or soluble Abeta oligomers in brain. These findings suggest that specifically reducing cerebral microvascular fibrillar Abeta deposition, in the absence of lowering either the total amount of Abeta or soluble Abeta oligomers in brain, may be sufficient to ameliorate microvascular amyloid-associated neuroinflammation.

Alzheimer Disease↗
PubMed2002

Vitamin E but not 17beta-estradiol protects against vascular toxicity induced by beta-amyloid wild type and the Dutch amyloid variant.

Amyloid beta-peptide (Abeta) fibril deposition on cerebral vessels produces cerebral amyloid angiopathy that appears in the majority of Alzheimer's disease patients. An early onset of a cerebral amyloid angiopathy variant called hereditary cerebral hemorrhage with amyloidosis of the Dutch type is caused by a point mutation in Abeta yielding Abeta(Glu22-->Gln). The present study addresses the effect of amyloid fibrils from both wild-type and mutated Abeta on vascular cells, as well as the putative protective role of antioxidants on amyloid angiopathy. For this purpose, we studied the cytotoxicity induced by Abeta(1-40 Glu22-->Gln) and Abeta(1-40 wild-type) fibrils on human venule endothelial cells and rat aorta smooth muscle cells. We observed that Abeta(Glu22-->Gln) fibrils are more toxic for vascular cells than the wild-type fibrils. We also evaluated the cytotoxicity of Abeta fibrils bound with acetylcholinesterase (AChE), a common component of amyloid deposits. Abeta(1-40 wild-type)-AChE fibrillar complexes, similar to neuronal cells, resulted in an increased toxicity on vascular cells. Previous reports showing that antioxidants are able to reduce the toxicity of Abeta fibrils on neuronal cells prompted us to test the effect of vitamin E, vitamin C, and 17beta-estradiol on vascular damage induced by Abeta(wild-type) and Abeta(Glu22-->Gln). Our data indicate that vitamin E attenuated significantly the Abeta-mediated cytotoxicity on vascular cells, although 17beta-estradiol and vitamin C failed to inhibit the cytotoxicity induced by Abeta fibrils.

Acetylcholinesterase↗