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PubMed2005

Amyloid mediates the association of apolipoprotein E e4 allele to cognitive function in older people.

BACKGROUND: The neurobiological changes underlying the association of the apolipoprotein E (APOE) e4 allele with level of cognition are poorly understood. OBJECTIVE: To test the hypothesis that amyloid load can account for (mediate) the association of the APOE e4 allele with level of cognition assessed proximate to death. METHODS: There were 44 subjects with clinically diagnosed Alzheimer's disease and 50 without dementia, who had participated in the Religious Orders Study. They underwent determination of APOE allele status, had comprehensive cognitive testing in the last year of life, and brain autopsy at death. The percentage area of cortex occupied by amyloid beta and the density of tau positive neurofibrillary tangles were quantified from six brain regions and averaged to yield summary measures of amyloid load and neurofibrillary tangles. Multiple regression analyses were used to examine whether amyloid load could account for the effect of allele status on level of cognition, controlling for age, sex, and education. RESULTS: Possession of at least one APOE e4 allele was associated with lower level of cognitive function proximate to death (p = 0.04). The effect of the e4 allele was reduced by nearly 60% and was no longer significant after controlling for the effect of amyloid load, whereas there was a robust inverse association between amyloid and cognition (p = 0.001). Because prior work had suggested that neurofibrillary tangles could account for the association of amyloid on cognition, we next examined whether amyloid could account for the effect of allele status on tangles. In a series of regression analyses, e4 was associated with density of tangles (p = 0.002), but the effect of the e4 allele was reduced by more than 50% and was no longer significant after controlling for the effect of amyloid load. CONCLUSION: These findings are consistent with a sequence of events whereby the e4 allele works through amyloid deposition and subsequent tangle formation to cause cognitive impairment.

Aged↗
PubMed1995

High-sensitivity diagnosis of AA amyloidosis using Congo red and immunohistochemistry detects missed amyloid deposits.

Biopsy diagnosis of early amyloid-A (AA) amyloidosis has often been difficult. Examination of 57 consecutive biopsy specimens from 42 patients with inflammatory pediatric diseases permitted comparison of the precision of biopsy amyloid diagnosis in six different laboratories (labs), which applied the following methods: Congo red alone (four unspecialized labs combined as Lab 1), Congo red and electron microscopy (Lab 2), or Congo red and immunohistochemistry using monoclonal antibodies (Lab 3). Lab 3 reexamined the diagnoses made by Lab 1 and Lab 2. Of the 42 patients, 17 patients with 32 biopsies were selected for this study based on the presence of amyloid in at least one biopsy. Whereas massive or no amyloid was concordantly recognized by all labs in 18 biopsies from nine patients, discordance was demonstrated in 14 biopsies from eight patients. Comparison of Labs 1-3 revealed amyloid in 12 rectal and 18 renal biopsies evaluated by Lab 3, whereas Lab 2 missed amyloid in two of 18 renal biopsies and Lab 1 missed amyloid in 11 of 12 rectal biopsies. Most amyloid was missed when only minute amounts of amyloid were present. Had our technique (Lab 3) been available at the time of biopsy, amyloid could have been diagnosed years earlier, thereby sparing the patient further biopsies and allowing initiation of earlier treatment before organ damage could occur.

Adolescent↗
PubMed1997

Effect of serum amyloid A on cellular affinity of low density lipoprotein.

Serum amyloid A, an apolipoprotein of high density lipoproteins, is also present to a lesser degree in low density lipoproteins and is co-localized with apolipoprotein B in atherosclerotic lesions. This study examined the effect of serum amyloid A on cellular affinity of low density lipoprotein in vitro. 125I-labelled low density lipoprotein, when loaded with recombinant serum amyloid A1 (acute phase isotype) or recombinant serum amyloid A4 (constitutive isotype), had enhanced binding to both human skin fibroblasts and a murine macrophage cell line, J774, while its degradation was slightly increased in both cells. The binding of oxidized low density lipoprotein to J774 cells was also enhanced by addition of recombinant serum amyloid A1 or serum amyloid A4, and degradation of oxidized low density lipoprotein was moderately enhanced by recombinant serum amyloid A1. The effects of recombinant serum amyloid A on cellular binding of labelled low density lipoprotein were not competed by non-labelled low density lipoprotein and were diminished in the presence of high density lipoprotein. These findings suggest that serum amyloid A in low density lipoprotein may promote association of low density lipoprotein with cells by non-specific adsorption, and high density lipoprotein may prevent such interactions by removal of serum amyloid A.

Adult↗
PubMed2006

The stability of monomeric intermediates controls amyloid formation: Abeta25-35 and its N27Q mutant.

The structure and stabilities of the intermediates affect protein folding as well as misfolding and amyloid formation. By applying Kramer's theory of barrier crossing and a Morse-function-like energy landscape, we show that intermediates with medium stability dramatically increase the rate of amyloid formation; on the other hand, very stable and very unstable intermediates sharply decrease amyloid formation. Remarkably, extensive molecular dynamics simulations and conformational energy landscape analysis of Abeta25-35 and its N27Q mutant corroborate the mathematical description. Both experimental and current simulation results indicate that the core of the amyloid structure of Abeta25-35 formed from residues 28-35. A single mutation of N27Q of Abeta25-35 makes the Abeta25-35 N27Q amyloid-free. Energy landscape calculations show that Abeta25-35 has extended intermediates with medium stability that are prone to form amyloids, whereas the extended intermediates for Abeta25-35 N27Q split into stable and very unstable species that are not disposed to form amyloids. The results explain the contribution of both alpha-helical and beta-strand intermediates to amyloid formation. The results also indicate that the structure and stability of the intermediates, as well as of the native folded and the amyloid states can be targeted in drug design. One conceivable approach is to stabilize the intermediates to deter amyloid formation.

Amino Acid Substitution↗
PubMed2002

Mechanistic studies of the process of amyloid fibrils formation by the use of peptide fragments and analogues: implications for the design of fibrillization inhibitors.

The process of amyloid fibrils formation is a common mechanism of a large number of unrelated infectious, genetic and spontaneous diseases. A partial list includes the bovine spongiform encephalopathy (BSE), Alzheimer's diseases, Type II diabetes, Creutzfeldt-Jakob disease, and various unrelated amyloidosis diseases. In spite of its significant clinical importance, the mechanism of fibrillization is not fully understood. This review discusses the recent advancements in the mechanistic studies of amyloid formation by the use peptide fragments and analogues of amyloid-forming proteins and polypeptides. The use of short peptide shed much light of the mechanism of amyloid fibrillization. Recent studies clearly prove that very short peptide fragments (as short as pentapeptides) can form well-ordered amyloidal structures. Therefore, the molecular recognition and self-assembly process that lead to the formation of order structures is being mediated by small structural elements. Analysis of short amyloid-related fragment by the use of an alanine-scan and sequence analysis of a variety of unrelated peptide and protein fragments suggest that aromatic interaction may play a central role in the process of amyloid formation. Inhibitors that are based on the short aromatic elements already demonstrated clear potency in arresting the process of amyloid fibrils formation. Taken together, the recent advancement in the mechanistic understanding of the process of amyloid fibrils formation has a major importance in the development of inhibitors of fibrillization that may serve as future therapeutic means to treat amyloid diseases.

Amyloid beta-Peptides↗
PubMed2006

Diagnostic and therapeutic potential of amyloid-reactive IgG antibodies contained in human sera.

Passive immunotherapy using fibril-reactive mAbs has been shown experimentally to reduce amyloid formation and also accelerate amyloidolysis. We now report that human sera, as well as various sources of pooled human IgG, including pharmacologic formulations of immune globulin i.v. (IGIV), contain Abs that specifically recognize fibrils formed from light chains and other amyloidogenic precursor proteins, including serum amyloid A, transthyretin, islet amyloid polypeptide, and amyloid beta 1-40 peptide, but notably, do not react with these molecules in their native nonfibrillar forms. After isolation of the Abs from IGIV via fibril-conjugated affinity column chromatography, the EC50-binding value for light chains and amyloid beta 1-40 peptide fibrils was approximately 15 nM-a magnitude approximately 200 and 70 times less than that of the unbound fraction and unfractionated product, respectively. Comparable reactivity was found in the case of those formed from serum amyloid A, transthyretin, and islet amyloid polypeptide. The purified Abs immunostained human amyloid tissue deposits and could inhibit fibrillogenesis, as shown in fibril formation and extension assays. Most importantly, in vivo reactivity was evidenced in a murine model when the enriched Abs were used to image amyloid, as well as expedite its removal. These promising experimental results suggest that fibril affinity-purified IGIV has potential as a diagnostic and therapeutic agent for patients with amyloid-associated disease.

Amyloid↗
PubMed1990

Serum amyloid A, an acute phase protein, inhibits platelet activation.

The effect of serum amyloid A, an acute phase protein, on platelet function was studied. Serum amyloid A was isolated and purified from sera of patients with recent trauma. Serum amyloid A inhibited thrombin-induced gel-filtered platelet aggregation. However, it did not inhibit aggregation induced by collagen or adenosine diphosphate, nor did it influence the aggregation of platelet-rich plasma activated with thrombin. Further studies of its effect on thrombin-induced activities showed that serum amyloid A, at concentrations of 25 to 100 micrograms/ml (which are found in mild acute events), suppressed the increase of cytosolic [Ca2+], thromboxane generation, and carbon 14-labeled serotonin release in a dose-dependent fashion. Serum amyloid A did not interfere with the clotting or amidolytic activities of thrombin. Therefore, the data suggest a protective role for serum amyloid A in thromboembolic disease by specific interaction with thrombin-induced platelet activation. Amyloid A protein also markedly inhibited thrombin-induced platelet aggregation. Because amyloid A is homologous to the N-terminal portion of serum amyloid A, the observed activity probably resides in that part of the molecule. This finding may be of importance in localization of the active site on serum amyloid A.

Acute-Phase Proteins↗
PubMed1991

Immunohistochemical localization of amyloid in Finnish hereditary amyloidosis with antibodies to gelsolin peptides.

The amyloid fibril protein in the Finnish type of familial amyloid polyneuropathy was recently identified as a fragment of gelsolin, a cytoskeletal and plasma protein with actin-modulating properties. Antibodies to three synthetic peptides of various parts of gelsolin were raised in rabbits and used in immunocytochemistry. The P-3 dodecapeptide, corresponding to the C-terminal region of the amyloid protein, elicited the best immunologic response and the P-3 antibodies were found suitable for use in immunohistochemistry and enzyme immunoassay. The P-3 antibodies specifically stained the amyloid deposits in various tissues including the skin, kidney, heart, thyroid gland, salivary gland, and rectum in patients with Finnish familial amyloid polyneuropathy. The staining was completely abolished by absorption of the antiserum with the synthetic dodecapeptide used for immunization, but not by a peptide of another region of the gelsolin molecule. The antibodies did not stain the amyloid of secondary amyloid A or of the myeloma-associated amyloid light chain. The results provide evidence for the relation between the amyloid deposited in the systemic tissues of patients with Finnish familial amyloid polyneuropathy and gelsolin, and demonstrate the utility of these anti-gelsolin antibodies in diagnostic immunohistochemistry.

Amyloid↗
PubMed1990

The relationship of amyloid plaques to cerebral capillaries in Alzheimer's disease.

The authors examined the hypothesis that senile plaques of Alzheimer's disease (AD) are formed by abnormal leakage of amyloidogenic precursors from brain capillaries by quantitative analysis of the spatial relationship between capillaries and amyloid plaques. Vibratome sections (40 mu) of the hippocampus, including the entorhinal cortex, obtained at autopsy from AD subjects, were immunostained with a monoclonal antibody to beta-protein and counterstained with rabbit serum to either the glucose transporter protein, a cerebral endothelial marker, or collagen type IV, a basal lamina marker. The authors found that while 60% to 77% of amyloid plaques were associated with capillaries, only 8% to 13% were penetrated by a capillary, the remainder being adjacent. To test whether 1) the area occupied by amyloid plaques or 2) the border zone (10-mu rim) surrounding amyloid plaques has a statistically higher density of capillaries than 3) the remaining gray matter, similarly double-stained 6-mu sections from five AD subjects were photographed and the capillary densities in the three areas calculated. Capillary density was significantly lower in 1) than in 3) and higher in 2) than in 3), while the combined area of 1) and 2) showed the same capillary density as 3). Similar results were obtained by using either the glucose transporter or the collagen type IV antibodies. Because capillary density is low within, and high in regions that immediately surround amyloid plaques, our findings suggest that amyloid plaques exclude capillaries or lead to their degeneration, or both. The latter possibility was investigated by triple-staining tissue sections with antibodies to beta-protein, glucose transporter, and collagen type IV. The proportion of glucose transporter-negative capillaries was not significantly different in areas inside or outside of the plaques. Thus, the authors found no evidence of basal lamina remnants consistent with capillary degeneration preferential to amyloid plaques. Although a small number of capillaries showed amyloid deposition just beneath the basement membrane, the authors conclude that capillaries play only a limited direct role, if any, in amyloid plaque formation, and that the apparent association of amyloid plaques and capillaries is no more than a chance contact.

Alzheimer Disease↗
PubMed1985

Pancreatic ganglioneuronal amyloid. Occurrence in diabetic cats with islet amyloidosis.

Amyloid in pancreatic ganglia and nerves (ganglioneuronal amyloid) was demonstrated in 4 of 8 diabetic cats with islet amyloid deposits. Eighteen nondiabetic cats (including 4 with islet amyloid) did not have detectable amyloid in pancreatic nerves or ganglia. Ganglioneuronal amyloid had staining characteristics identical to those previously reported for islet amyloid, including 1) congophilia, 2) resistance to oxidation by KMnO4, 3) immunoreactivity (PAP technique) with antiserum to a B-chain-rich insulin fraction, and 4) no reactivity with antisera to insulin, glucagon, or somatostatin. Nonneuronal cells with insulin, glucagon, and somatostatin immunoreactivity were seen in many pancreatic ganglia and nerves; and in a few instances, B cells were found near ganglioneuronal amyloid deposits. The premise that these ganglioneuronal amyloid deposits (like islet amyloid) are insulin-related is supported by their immunoreactivity with antiserum to B-chain-rich insulin and the demonstration of B cells in pancreatic ganglia and nerves.

Amyloid↗
PubMed1993

Scintigraphic quantification and serial monitoring of human visceral amyloid deposits provide evidence for turnover and regression.

Radiolabelled serum amyloid P component scintigraphy provides information on the diagnosis and distribution of amyloid which was not previously available. A simple reproducible method for quantifying the uptake of 123I-labelled serum amyloid P component into individual livers, spleens and kidneys was devised and evaluated in 22 patients with different types of systemic amyloidosis. Prospective studies in 10 patients were undertaken in order to monitor aspects of the natural history of visceral amyloid deposits. Although measurements of tracer uptake were not as discriminating for diagnostic purposes as the opinions of two highly experienced visual observers, the availability of objective scintigraphic parameters should facilitate interpretation of serum amyloid P component scans in centres unfamiliar with the technique. The follow-up studies demonstrated several intriguing features of amyloidogenesis. There was very rapid progression of deposits in some individuals with differential rates of accretion in different organs. The single patient with AL amyloidosis treated with cytotoxic drugs showed substantial regression of hepatic amyloid deposits whilst his splenic amyloid increased. His spleen was then removed and further regression of the hepatic amyloid was observed. It is concluded that quantitative serum amyloid P component scintigraphy is a useful method for assessing visceral amyloid and that the deposits not only progress at extremely variable rates, but can evidently also be mobilized. These findings encourage active therapeutic approaches in the management of amyloidosis.

Adult↗
PubMed1996

Cerebral amyloid angiopathies.

The cerebral amyloid angiopathies comprise a heterogeneous group of disorders that are characterized clinically by ischaemic and/or haemorrhagic strokes, and histologically by deposition of amyloid in the wall of leptomeningeal and cerebral cortical blood vessels. On the basis of the molecular composition of the amyloid, two forms can be distinguished. Cystatin C amyloid angiopathy is a rare autosomal dominant disorder confined to several families from Iceland. beta-amyloid cerebral amyloid angiopathies may be hereditary or sporadic, and share clinical, pathological and biochemical features with Alzheimer's disease. Both types of vascular amyloid derive from precursor proteins synthesized in situ by astrocytes (cystatin C) or smooth muscle cells (beta-amyloid), and induce progressive degeneration of smooth muscle cells, blood vessel rupture and haemodynamic changes. In recent years, it has been reported that mutations underlying both types of hereditary cerebral amyloid angiopathy directly involve the gene encoding the precursor protein. These findings have increased our understanding of the amyloidogenic mechanisms and allowed preclinical diagnosis. Nevertheless, the aetiopathogenetic factors involved in the more frequent sporadic form of amyloid angiopathy remain unknown.

Animals↗
PubMedDate not supplied

Amyloid deposits of immunohistochemically different classes in the ligamentum flavum in biopsies from patients with herniated discs or lumbar spinal stenosis.

Ligamenta flava of 100 patients (n = 107 tissue blocks) were examined for the presence of amyloid by means of polarization microscopy after staining with Congo red. Ninety-three ligamenta flava were resected due to operation of herniated discs while 14 ligamenta flava were obtained after surgical treatment of lumbar spinal stenosis. Amyloid of various amounts (score I-III) and 4 morphologically different appearances were detected in the ligamenta flava of 12 patients. In 6 patients small amyloid deposits were seen along elastic fibres (pattern 1) and/or minute, comma-like deposits in certain areas (pattern 2). In 5 other patients amyloid deposits in form of large lumps were present (pattern 3) intermingled with deposits of pattern 1 and/or 2. Only 1 patient could be detected with amyloid deposits partly associated with blood vessels (pattern 4). The amyloid-containing tissue samples (n = 13) were immunohistochemically analyzed using anti-AA-, anti-A lambda-, anti-A kappa-, anti-ATTR- and anti-A beta 2m-antibodies which are able to identify the major known amyloid classes of tissue sections. Tissues with pattern 1 and 2 amyloid deposits did not react above background with any of the antibodies. In contrast, the 5 patients with pattern 3 amyloid stained strongly with anti-ATTR but not with the other antisera. In this group, therefore, senile systemic amyloid (sporadic ATTR) was also identified which had not been detected at this site before. Consistent with this finding is the advanced age of these patients which was seen to be significantly higher than the average age of the entire group of patients examined.

Adult↗
PubMed2001

Neuronal and glial beta-secretase (BACE) protein expression in transgenic Tg2576 mice with amyloid plaque pathology.

We measured tissue distribution and expression pattern of the beta-site amyloid precursor protein (APP)-cleaving enzyme (BACE) in the brains of transgenic Tg2576 mice that show amyloid pathology. BACE protein was expressed at high levels in brain; at lower levels in heart and liver; and at very low levels in pancreas, kidney, and thymus and was almost absent in spleen and lung when assayed by Western blot analysis. We observed strictly neuronal expression of BACE protein in the brains of nontransgenic control mice, with the most robust immunocytochemical labeling present in the cerebral cortex, hippocampal formation, thalamus, and cholinergic basal forebrain nuclei. BACE protein levels did not differ significantly between control and transgenic mice or as a result of aging. However, in the aged, 17-month-old Tg2576 mice there was robust amyloid plaque formation, and BACE protein was also present in reactive astrocytes present near amyloid plaques, as shown by double immunofluorescent labeling and confocal laser scanning microscopy. The lack of astrocytic BACE immunoreactivity in young transgenic Tg2576 mice suggests that it is not the APP overexpression but rather the amyloid plaque formation that stimulates astrocytic BACE expression in Tg2576 mice. Our data also suggest that the neuronal overexpression of APP does not induce the overexpression of its metabolizing enzyme in neurons. Alternatively, the age-dependent accumulation of amyloid plaques in the Tg2576 mice does not require increased neuronal expression of BACE. Our data support the hypothesis that neurons are the primary source of beta-amyloid peptides in brain and that astrocytic beta-amyloid generation may contribute to amyloid plaque formation at later stages or under conditions when astrocytes are activated.

Alzheimer Disease↗
PubMed2000

Senile dementia associated with amyloid beta protein angiopathy and tau perivascular pathology but not neuritic plaques in patients homozygous for the APOE-epsilon4 allele.

Amyloid beta protein deposition in cortical and leptomeningeal vessels, causing the most common type of cerebral amyloid angiopathy, is found in sporadic and familial Alzheimer's disease (AD) and is the principal feature in the hereditary cerebral hemorrhage with amyloidosis, Dutch type. The presence of the Apolipopriotein E (APOE)-epsilon4 allele has been implicated as a risk factor for AD and the development of cerebral amyloid angiopathy in AD. We report clinical, pathological and biochemical studies on two APOE-epsilon4 homozygous subjects, who had senile dementia and whose main neuropathological feature was a severe and diffuse amyloid angiopathy associated with perivascular tau neurofibrillary pathology. Amyloid beta protein and ApoE immunoreactivity were observed in leptomeningeal vessels as well as in medium-sized and small vessels and capillaries in the parenchyma of the neocortex, hippocampus, thalamus, cerebellum, midbrain, pons, and medulla. The predominant peptide form of amyloid beta protein was that terminating at residue Val40, as determined by immunohistochemistry, amino acid sequence and mass spectrometry analysis. A crown of tau-immunopositive cell processes was consistently present around blood vessels. DNA sequence analysis of the Amyloid Precursor Protein gene and Presenilin-1 (PS-1) gene revealed no mutations. In these APOE-epsilon4 homozygous patients, the pathological process differed from that typically seen in AD in that they showed a heavy burden of perivascular tau-immunopositive cell processes associated with severe amyloid beta protein angiopathy, neurofibrillary tangles, some cortical Lewy bodies and an absence of neuritic plaques. These cases emphasize the concept that tau deposits may be pathogenetically related to amyloid beta protein deposition.

Aged↗
PubMed2005

Proteolytic mechanisms in amyloid-beta metabolism: therapeutic implications for Alzheimer's disease.

The accumulation of the amyloid-beta peptide, the main constituent of the "amyloid plaque", is widely considered to be the key pathological event in Alzheimer's disease. Amyloid-beta is produced from the amyloid precursor protein through the action of the proteases beta-secretase and gamma-secretase. Alternative cleavage of amyloid precursor protein by the enzyme alpha-secretase precludes amyloid-beta production. In addition, several proteases are involved in the degradation of amyloid-beta. This review focuses on the proteolytic mechanisms of amyloid-beta metabolism. An increasingly detailed understanding of proteolysis in both amyloid-beta deposition and clearance has identified some of these proteases as potential therapeutic targets for Alzheimer's disease. A more complex knowledge of these proteases takes us one step closer to developing "disease-modifying" therapies, but these advances also emphasize that significant challenges must be overcome before clinically effective drugs to treat Alzheimer's disease become a reality.

Alzheimer Disease↗
PubMed2006

Deposition of mouse amyloid beta in human APP/PS1 double and single AD model transgenic mice.

The deposition of amyloid beta (Abeta) peptides and neurofibrillary tangles are the two characteristic pathological features of Alzheimer's disease (AD). To investigate the relation between amyloid precursor protein (APP) production, amyloid beta deposition and the type of Abeta in deposits, i.e., human and/or mouse, we performed a histopathological analysis, using mouse and human specific antibodies, of the neocortex and hippocampus in 6, 12 and 19 months old APP/PS1 double and APP and PS1 single transgenic mice. There was a significant correlation between the human amyloid beta deposits and the intrinsic rodent amyloid beta deposits, that is, all plaques contained both human and mouse Abeta, and the diffuse amyloid beta deposits also colocalized human and mouse Abeta. Furthermore, some blood vessels (mainly leptomeningeal vessels) show labeling with human Abeta, and most of these vessels also label with mouse Abeta. Our findings demonstrate that the human amyloid deposits in APP/PS1 transgenic mice are closely associated with mouse Abeta, however, they do not precisely overlap. For instance, the core of plaques consists of primarily human Abeta, whereas the rim of the plaque contains both human and mouse amyloid beta, similarly, human and mouse Abeta are differentially localized in the blood vessel wall. Finally, as early as amyloid beta deposits can be detected, they show the presence of both human and mouse Abeta. Together, these data indicate that mouse Abeta is formed and deposited in significant amounts in the AD mouse brain and that it is deposited together with the human Abeta.

Alzheimer Disease↗
PubMed2002

Conformational Abs recognizing a generic amyloid fibril epitope.

Disease-related amyloid fibrils appear to share a common, but poorly understood, structure. We describe here the generation and preliminary characterization of two conformation-specific mAbs, WO1 and WO2, that bind to the amyloid fibril state of the Alzheimer's peptide A beta(1-40) but not to its soluble, monomeric state. Surprisingly, these Abs also bind to other disease-related amyloid fibrils and amyloid-like aggregates derived from other proteins of unrelated sequence, such as transthyretin, islet amyloid polypeptide, beta(2)-microglobulin, and polyglutamine. At the same time, WO1 and WO2 do not bind to the native protein precursors of these amyloids, nor do they bind to other kinds of protein aggregates. This new class of Abs associated with a fundamental amyloid-folding motif appear to recognize a common conformational epitope with little apparent dependence on amino acid side chain information. These Abs should contribute to the understanding of amyloid structure, assembly, and toxicity and also may benefit the development of diagnostic and therapeutic agents for amyloid diseases.

Amyloid↗