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At least 415 records · Page 23Linked to original sources
PubMed2005

AlphaB-crystallin, a small heat-shock protein, prevents the amyloid fibril growth of an amyloid beta-peptide and beta2-microglobulin.

AlphaB-crystallin, a small heat-shock protein, exhibits molecular chaperone activity. We have studied the effect of alphaB-crystallin on the fibril growth of the Abeta (amyloid beta)-peptides Abeta-(1-40) and Abeta-(1-42). alphaB-crystallin, but not BSA or hen egg-white lysozyme, prevented the fibril growth of Abeta-(1-40), as revealed by thioflavin T binding, total internal reflection fluorescence microscopy and CD spectroscopy. Comparison of the activity of some mutants and chimaeric alpha-crystallins in preventing Abeta-(1-40) fibril growth with their previously reported chaperone ability in preventing dithiothreitol-induced aggregation of insulin suggests that there might be both common and distinct sites of interaction on alpha-crystallin involved in the prevention of amorphous aggregation of insulin and fibril growth of Abeta-(1-40). alphaB-crystallin also prevents the spontaneous fibril formation (without externally added seeds) of Abeta-(1-42), as well as the fibril growth of Abeta-(1-40) when seeded with the Abeta-(1-42) fibril seed. Sedimentation velocity measurements show that alphaB-crystallin does not form a stable complex with Abeta-(1-40). The mechanism by which it prevents the fibril growth differs from the known mechanism by which it prevents the amorphous aggregation of proteins. alphaB-crystallin binds to the amyloid fibrils of Abeta-(1-40), indicating that the preferential interaction of the chaperone with the fibril nucleus, which inhibits nucleation-dependent polymerization of amyloid fibrils, is the mechanism that is predominantly involved. We found that alphaB-crystallin prevents the fibril growth of beta2-microglobulin under acidic conditions. It also retards the depolymerization of beta2-microglobulin fibrils, indicating that it can interact with the fibrils. Our study sheds light on the role of small heat-shock proteins in protein conformational diseases, particularly in Alzheimer's disease.

Amyloid↗
PubMed2003

Characterization of amyloid beta peptides from brain extracts of transgenic mice overexpressing the London mutant of human amyloid precursor protein.

Alzheimer's disease (AD) is marked by the presence of neurofibrillary tangles and amyloid plaques in the brain of patients. To study plaque formation, we report on further quantitative and qualitative analysis of human and mouse amyloid beta peptides (Abeta) from brain extracts of transgenic mice overexpressing the London mutant of human amyloid precursor protein (APP). Using enzyme-linked immunosorbant assays (ELISAs) specific for either human or rodent Abeta, we found that the peptides from both species aggregated to form plaques. The ratios of deposited Abeta1-42/1-40 were in the order of 2-3 for human and 8-9 for mouse peptides, indicating preferential deposition of Abeta42. We also determined the identity and relative levels of other Abeta variants present in protein extracts from soluble and insoluble brain fractions. This was done by combined immunoprecipitation and mass spectrometry (IP/MS). The most prominent peptides truncated either at the carboxyl- or the amino-terminus were Abeta1-38 and Abeta11-42, respectively, and the latter was strongly enriched in the extracts of deposited peptides. Taken together, our data indicate that plaques of APP-London transgenic mice consist of aggregates of multiple human and mouse Abeta variants, and the human variants that we identified were previously detected in brain extracts of AD patients.

Alzheimer Disease↗
PubMed2004

A nontransgenic mouse model shows inducible amyloid-beta (Abeta) peptide deposition and elucidates the role of apolipoprotein E in the amyloid cascade.

The amyloid-beta (Abeta) peptide, a major pathological hallmark of Alzheimer's disease (AD), undergoes a cascade of interactions resulting in the formation of soluble aggregates and their conversion in the brain to insoluble deposits and mature senile plaques. Furthermore, the apoE4 isoform of apolipoprotein E (apoE), which is the major genetic risk factor of AD, is associated with increased Abeta deposition. It is not known how the different Abeta aggregates in the amyloid cascade are formed, contribute to the pathogenesis of AD, or are affected by apoE4. To investigate the initial aggregation stages underlying the amyloid cascade in vivo and how apoE affects them, we examined the effects of prolonged inhibition and subsequent reactivation of the Abeta-degrading protease neprilysin on deposition, disaggregation, and fibrillization of Abeta in apoE-transgenic and control mice. In control mice, intracerebroventricular infusion of thiorphan, which inhibits neprilysin, induced Abeta42 and Abeta40 deposition and fibrillization. On termination of thiorphan treatment, the number of Abeta deposits decreased, whereas the fibrillar Abeta deposits were unaffected. Similar treatments in apoE-deficient mice and mice transgenic for human apoE4 or apoE3 revealed that apoE4 enhances specifically the nucleation and aggregation of immunopositive Abeta deposits and that reversible disaggregation of these deposits and their irreversible conversion to fibrillar deposits are stimulated similarly by the different apoE isoforms. Deposition of Abeta and its enhancement by apoE4 were accompanied by increased astrogliosis both far from and near the Abeta deposits, suggesting that astrogliosis might be triggered by both insoluble and soluble Abeta aggregates.

Alzheimer Disease↗
PubMed1994

Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure.

Human serum amyloid P component (SAP) is a normal plasma protein and the precursor of amyloid P component (AP), a universal constituent of the abnormal tissue deposits in amyloidosis, including Alzheimer disease. We show here that its single N-linked biantennary oligosaccharide does not display the microheterogeneity usually characteristic of glycoproteins. The protein and the glycan structures of AP were also invariant, their resistance to degradation suggesting a role in persistence of amyloid deposits. Asialo-SAP was rapidly cleared from the circulation in mice by a mechanism dependent on terminal galactose residues and was catabolized in hepatocytes. However blockade of this pathway did not affect the clearance of native SAP. Rapid hepatic uptake and catabolism of human asialo-SAP in man were also directly demonstrated. The protein and glycan homogeneity of SAP and the integrity of AP suggest that the complete glycoprotein structure is important for the normal and the pathophysiological functions of this molecule.

Amyloid↗
PubMed1994

Transthyretin sequesters amyloid beta protein and prevents amyloid formation.

The cardinal pathological features of Alzheimer disease are depositions of aggregated amyloid beta protein (A beta) in the brain and cerebrovasculature. However, the A beta is found in a soluble form in cerebrospinal fluid in healthy individuals and patients with Alzheimer disease. We postulate that sequestration of A beta precludes amyloid formation. Failure to sequester A beta in Alzheimer disease may result in amyloidosis. When we added A beta to cerebrospinal fluid of patients and controls it was rapidly sequestered into stable complexes with transthyretin. Complexes with apolipoprotein E, which has been shown to bind A beta in vitro, were not observed in cerebrospinal fluid. Additional in vitro studies showed that both purified transthyretin and apolipoprotein E prevent amyloid formation.

Amino Acid Sequence↗
PubMed1995

Intracellular accumulation of beta-amyloid in cells expressing the Swedish mutant amyloid precursor protein.

beta-Amyloid (beta A) is a normal metabolic product of the amyloid precursor protein (APP) that accumulates in senile plaques in Alzheimer's disease. Cells that express the Swedish mutant APP (Sw-APP) associated with early onset Alzheimer's disease overproduce beta A. In this report, we show that expression of Sw-APP gives rise to cell-associated beta A, which is not detected in cells that express wild-type APP. Cell-associated beta A is rapidly generated, is trypsin-resistant, and is not derived from beta A uptake, indicating that it is generated from intracellular processing of Sw-APP. Intracellular and secreted beta A are produced with different kinetics. The generation of intracellular beta A is partially resistant to monensin and a 20 degrees C temperature block but is completely inhibited by brefeldin A, suggesting that it occurs in the Golgi complex. Monensin, brefeldin A, and a 20 degrees C temperature block almost completely inhibit beta A secretion without causing increased cellular retention of beta A, suggesting that secreted beta A is generated in a post-Golgi compartment. These results suggest that the metabolism of Sw-APP gives rise to intracellular and secreted forms of beta A through distinct processing pathways. Pathological conditions may therefore alter both the level and sites of accumulation of beta A. It remains to be determined whether the intracellular form of beta A plays a role in the formation of amyloid plaques.

Alzheimer Disease↗
PubMed1996

The alternatively spliced Kunitz protease inhibitor domain alters amyloid beta protein precursor processing and amyloid beta protein production in cultured cells.

The insoluble amyloid deposited extracellularly in the brains of patients with Alzheimer's disease (AD) is composed of amyloid beta protein, a approximately 4-kDa secreted protein that is derived from a set of large proteins collectively referred to as the amyloid beta protein precursor (betaAPP). During normal processing the betaAPP is cleaved by beta secretase, producing a large NH2-terminal secreted derivative (sAPPbeta) and a COOH-terminal fragment beginning at Abeta1, which is subsequently cleaved by gamma secretase releasing secreted Abeta. Most secreted Abeta is Abeta1-40, but approximately 10% of secreted Abeta is Abeta1-42. Alternative betaAPP cleavage by alpha secretase produces a slightly longer NH2-terminal secreted derivative (sAPPalpha) and a COOH-terminal fragment beginning at Abeta17, which is subsequently cleaved by gamma secretase releasing a approximately 3-kDa secreted form of Abeta (P3). Several of the betaAPP isoforms that are produced by alternative splicing contain a 56-amino acid Kunitz protease inhibitor (KPI) domain known to inhibit proteases such as trypsin and chymotrypsin. To determine whether the KPI domain influences the proteolytic cleavages that generate Abeta, we compared Abeta production in transfected cells expressing human KPI-containing betaAPP751 or KPI-free betaAPP695. We focused on Abetas ending at Abeta42 because these forms appear to be most relevant to AD. Using specific sandwich enzyme-linked immunosorbent assays, we analyzed full-length Abeta1-42 and total Abeta ending at Abeta42 (Abeta1-42 + P3(42)). In addition, we analyzed the large secreted derivatives produced by alpha secretase (sAPPalpha) and beta secretase (sAPPbeta). In mouse teratocarcinoma (P19) cells expressing betaAPP695 or betaAPP751, expression of the KPI-containing betaAPP751 resulted in the secretion of a lower percentage of P3(42) and sAPPalpha and a correspondingly higher percentage of Abeta1-42 and sAPPbeta. Similar results were obtained in human embryonic kidney (293) cells. These results indicate that expression of the KPI domain reduces alpha secretase cleavage so that less P3 and relatively more full-length Abeta are produced. Thus, in human brain and in animal models of AD, the amount of KPI-containing betaAPP produced may be an important factor influencing Abeta deposition.

Alternative Splicing↗
PubMed1998

X11 interaction with beta-amyloid precursor protein modulates its cellular stabilization and reduces amyloid beta-protein secretion.

The protein interaction domain of the neuronal protein X11 binds to the YENPTY motif within the cytoplasmic domain of beta-amyloid precursor protein (betaAPP). Amyloid-beta protein (Abeta), the major constituent of the amyloid deposited in brain of Alzheimer's disease patients, is generated by proteolytic processing of betaAPP, which occurs in part following betaAPP internalization. Because the YENPTY motif has a role in the internalization of betaAPP, the effect of X11 binding on betaAPP processing was studied in mouse neuroblastoma N2a, human embryonic kidney 293, monkey kidney COS-1, and human glial U251 cell lines transfected with wild type or mutated betaAPP cDNAs. Secretion of soluble betaAPP via alpha-secretase activity increased significantly in cells transfected with betaAPP variants containing mutations that impair interaction with X11 when compared with cells transfected with wild type cDNA. Cotransfection of betaAPP and X11 caused retention of cellular betaAPP, decreased secretion of sbetaAPPalpha, and decreased Abeta secretion. Thus, betaAPP interaction with the protein interaction domain of X11 stabilizes cellular betaAPP and thereby participates in the regulation of betaAPP processing pathways.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Regulation of beta-amyloid secretion by FE65, an amyloid protein precursor-binding protein.

The principal component of Alzheimer's amyloid plaques, Abeta, derives from proteolytic processing of the Alzheimer's amyloid protein precursor (APP). FE65 is a brain-enriched protein that binds to APP. Although several laboratories have characterized the APP-FE65 interaction in vitro, the possible relevance of this interaction to Alzheimer's disease has remained unclear. We demonstrate here that APP and FE65 co-localize in the endoplasmic reticulum/Golgi and possibly in endosomes. Moreover, FE65 increases translocation of APP to the cell surface, as well as both alphaAPPs and Abeta secretion. The dramatic (4-fold) FE65-dependent increase in Abeta secretion suggests that agents which inhibit the interaction of FE65 with APP might reduce Abeta secretion in the brain and therefore be useful for preventing or slowing amyloid plaque formation.

Amyloid beta-Peptides↗
PubMed2001

Amyloid precursor protein and amyloid beta peptide in human platelets. Role of cyclooxygenase and protein kinase C.

The main component of Alzheimer's disease (AD) senile plaques is amyloid-beta peptide (Abeta), a proteolytic fragment of the amyloid precursor protein (APP). Platelets contain both APP and Abeta and may contribute to the perivascular amyloid deposition seen in AD. However, no data are available concerning the biochemical mechanism(s) involved in their formation and release by these cells. We found that human platelets released APP and Abeta following activation with collagen or arachidonic acid. Inhibition of platelet cyclooxygenase (COX) reduced APP but not Abeta release following those stimuli. In contrast, activation of platelets by thrombin and calcium ionophore caused release of both APP and Abeta in a COX-independent fashion. Ex vivo studies showed that, despite suppression of COX activity, administration of aspirin did not modify Abeta or APP levels in serum or plasma, suggesting that this enzyme plays only a minor role in vivo. We examined the regulation of APP cleavage and release from activated platelets and found that cleavage requires protein kinase C (PKC) activity and is regulated by the intracellular second messengers phosphatidylinositol 2-phosphate and Ca(2+). Our data provide the first evidence that in human platelets COX is a minor component of APP secretion whereas PKC plays a major role in the secretory cleavage of APP. By contrast, Abeta release may represent secretion of preformed peptide and is totally independent of both COX and PKC activity.

Amyloid beta-Peptides↗
PubMed2001

Identification of a heparin binding domain in the N-terminal cleavage site of pro-islet amyloid polypeptide. Implications for islet amyloid formation.

Islet amyloid deposits are a characteristic pathologic lesion of the pancreas in type 2 diabetes and are composed primarily of the islet beta cell peptide islet amyloid polypeptide (IAPP or amylin) as well as the basement membrane heparan sulfate proteoglycan perlecan. Impaired processing of the IAPP precursor has been implicated in the mechanism of islet amyloid formation. The N- and C-terminal cleavage sites where pro-IAPP is processed by prohormone convertases contain a series of basic amino acid residues that we hypothesized may interact with heparan sulfate proteoglycans. This possibility was tested using affinity chromatography by applying synthetic fragments of pro-IAPP to heparin-agarose and heparan sulfate-Sepharose. An N-terminal human pro-IAPP fragment (residues 1-30) was retained by both heparin-agarose and heparan sulfate-Sepharose, eluting at 0.18 m NaCl at pH 7.5. Substitution of alanine residues for two basic residues in the N-terminal cleavage site abolished heparin and heparan sulfate binding activity. At pH 5.5, the affinity of the wild-type peptide for heparin/heparan sulfate was increased, implying a role for histidine residues at positions 6 and 28 of pro-IAPP. A C-terminal pro-IAPP fragment (residues 41-67) had no specific affinity for either heparin or heparan sulfate, and the N- or C-terminal fragments had only weak affinity for chondroitin sulfate. These data suggest that monomeric N-terminal human pro-IAPP contains a heparin binding domain that is lost during normal processing of pro-IAPP.

Amino Acid Sequence↗
PubMed2001

Effects of the beta-amyloid and carboxyl-terminal fragment of Alzheimer's amyloid precursor protein on the production of the tumor necrosis factor-alpha and matrix metalloproteinase-9 by human monocytic THP-1.

To explore the direct role of beta-amyloid (Abeta) and carboxyl-terminal fragments of amyloid precursor protein in the inflammatory processes possibly linked to neurodegeneration associated with Alzheimer's disease, the effects of the 105-amino acid carboxyl-terminal fragment (CT(105)) of amyloid precursor protein on the production of tumor necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-9 (MMP-9) were examined in a human monocytic THP-1 cell line and compared with that of Abeta. CT(105) elicited a marked increase in TNF-alpha and MMP-9 production in the presence of interferon-gamma in a dose- and time-dependent manner. Similar patterns were obtained with Abeta despite its low magnitude of induction. Autocrine TNF-alpha is likely to be a main mediator of the induction of MMP-9 because the neutralizing antibody to TNF-alpha inhibits MMP-9 production. Genistein, a specific inhibitor of tyrosine kinase, dramatically diminished both TNF-alpha secretion and subsequent MMP-9 release in response to CT(105) or Abeta. Furthermore, PD98059 and SB202190, specific inhibitors of ERK or p38 MAPK respectively, efficiently suppressed CT(105)-induced effects whereas only PD98059 was effective at reducing Abeta-induced effects. Our results suggest that CT(105) in combination with interferon-gamma might serve as a more potent activator than Abeta in triggering inflammatory processes and that both tyrosine kinase and MAPK signaling pathways may represent potential therapeutic targets for the control of Alzheimer's disease progression.

Alzheimer Disease↗
PubMed2005

Amyloid precursor-like protein 1 influences endocytosis and proteolytic processing of the amyloid precursor protein.

Ectodomain shedding of the amyloid precursor protein (APP) is a key regulatory step in the generation of the Alzheimer disease amyloid beta peptide (Abeta). The molecular mechanisms underlying the control of APP shedding remain little understood but are in part dependent on the low density lipoprotein receptor-related protein (LRP), which is involved in APP endocytosis. Here, we show that the APP homolog APLP1 (amyloid precursor-like protein 1) influences APP shedding. In human embryonic kidney 293 cells expression of APLP1 strongly activated APP shedding by alpha-secretase and slightly reduced beta-secretase cleavage. As revealed by domain deletion analysis, the increase in APP shedding required the NPTY amino acid motif within the cytoplasmic domain of APLP1. This motif is conserved in APP and is essential for the endocytosis of APP and APLP1. Unrelated membrane proteins containing similar endocytic motifs did not affect APP shedding, showing that the increase in APP shedding was specific to APLP1. In LRP-deficient cells APLP1 no longer induced APP shedding, suggesting that in wild-type cells APLP1 interferes with the LRP-dependent endocytosis of APP and there by increases APP alpha-cleavage. In fact, an antibody uptake assay revealed that expression of APLP1 reduced the rate of APP endocytosis. In summary, our study provides a novel mechanism for APP shedding, in which APLP1 affects the endocytosis of APP and makes more APP available for alpha-secretase cleavage.

Amino Acid Motifs↗
PubMed2002

Brain clearance of Alzheimer's amyloid-beta40 in the squirrel monkey: a SPECT study in a primate model of cerebral amyloid angiopathy.

Squirrel monkey is a valuable model to study pathogenesis of cerebrovascular amyloid angiopathy (CAA). Previous studies suggested that circulating amyloid-beta40 peptide (Abeta40) crosses the blood-brain barrier (BBB) and may therefore enhance cerebrovascular amyloidosis in aged squirrel monkeys. In the present study, we used single photon emission computed tomography (SPECT) to determine elimination of 123I-Abeta40 and 99mTc-DTPA, an extracellular marker, from the brain in squirrel monkeys at different age. Following intracerebral microinfusions, the time-activity brain clearance curves indicated bi-exponential removal of 123I-Abeta40 with an initial rapid washout (1.1 < or = t 1/2 < or = 2.7 h). This, plus the observed appearance of 123I-radioactivity in plasma suggest significant brain-to-blood transport. In contrast, 99mTc-DTPA was removed slowly by brain interstitial fluid bulk flow (monoexponential decay with 6.8 < or = t 1/2 < or = 16.8 h). A comparison of three middle aged (11-16 years old) vs. two old (22 yrs old) monkeys was consistent with an age-related decline in the BBB capacity to remove 123I-Abeta from the brain. This correlated with an age-dependent increase in A1beta40/42 cerebrovascular immunoreactivity and amyloid deposition. Thus, vascular clearance plays an important role in reducing Abeta levels in the squirrel monkey brain and impaired Abeta40 elimination across the BBB may contribute to the development of CAA.

Alzheimer Disease↗
PubMed1999

Late-onset familial amyloid polyneuropathy type I (transthyretin Met30-associated familial amyloid polyneuropathy) unrelated to endemic focus in Japan. Clinicopathological and genetic features.

Clinicopathological and genetic features were assessed on 35 Japanese families affected by late-onset familial amyloid polyneuropathy type I (transthyretin Met30-associated familial amyloid polyneuropathy, FAP TTR Met30) whose siblings were unrelated to endemic Japanese foci. In these patients (50 years or older), the most common initial symptom was paraesthesias in the legs. Autonomic symptoms were generally mild and did not seriously affect daily activities. The male-to-female ratio was extremely high (10.7 : 1). A family history was evident in only 11 out of 35 families, and other patients were apparently sporadic. The rate of penetrance was very low. Symptomatic siblings of familial cases showed a late age of onset, male preponderance and clinical features similar to those of the probands. Asymptomatic carriers, predominantly female, were detected relatively late in life. The geographical distribution of these late-onset, FAP TTR Met30 cases was scattered throughout Japan. In three autopsy cases and 20 sural nerve biopsy specimens, neurons in sympathetic and sensory ganglia were relatively preserved. Amyloid deposition was seen in the peripheral nervous system, particularly in the sympathetic ganglia, dorsal root ganglia and proximal nerve trunks such as sciatic nerve. These abnormalities were milder than those seen in typical early-onset FAP TTR Met30, as observed in two Japanese endemic foci of this disease. While axonal degeneration was prominent in myelinated fibres, resulting in severe fibre loss, unmyelinated fibres were relatively preserved. Our cases of late-onset FAP TTR Met30 showed features distinct from those of typical early-onset FAP TTR Met30 that occurred in the two Japanese endemic foci. Factors responsible for clinicopathological differences between these two forms of FAP TTR Met30 need to be identified.

Action Potentials↗
PubMed2004

Amino-truncated amyloid beta-peptide (Abeta5-40/42) produced from caspase-cleaved amyloid precursor protein is deposited in Alzheimer's disease brain.

Caspase activation and apoptosis are implicated in Alzheimer's disease (AD). In view of the finding that the amyloid precursor protein (APP) undergoes caspase-mediated cleavage in the cytoplasmic region, we analyzed amyloid beta-peptide (Abeta) production in human neuronal and nonneuronal cells expressing wild-type APP and the caspase-cleaved form of APP (APPDeltaC). Biochemical analyses, including immunoprecipitation/mass spectrometry, revealed that APPDeltaC-expressing cells secrete increased levels of amino-terminally truncated Abeta5-40/42 and reduced levels of Abeta1-40/42, compared with wild-type APP-expressing cells. We propose that Abeta5-40/42 is derived from alternative beta-cleavage of APP by alpha-secretase-like protease(s), based on data from treatment of cells with inhibitors of BACE and alpha-secretase. Apoptosis induction resulted in this alternative cleavage of APP in wild-type APP-expressing cells. Moreover, immunohistochemical staining of the AD brain with an end-specific antibody to Abeta5-40/42 revealed peptide deposits in vascular lesions with amyloid angiopathy. The data collectively suggest that caspase cleavage of APP leads to increased production and deposition of Abeta5-40/42 in the AD brain, and highlight the significance of amino-truncated Abeta in the pathogenesis of AD.

Alzheimer Disease↗
PubMed1984

A second component in bovine AA amyloid fibrils not identical with protein AA is essential for AA amyloid fibrillogenesis.

Amyloid fibrils were isolated from the renal papillae and glomeruli of cows with spontaneous AA amyloidosis. The fibrils were solubilized by treatment with guanidine hydrochloride (Gu HCl) and subjected to gel filtration on Sephacryl S-200. Two other fractions were obtained beside the void volume and the AA fractions. Reaggregation studies were performed by dialysing the fractions, separately or in combinations, against Gu-HCl-free solutions. Protein AA alone (about 10 kd) appeared not to precipitate. The other fractions alone and the combinations of fractions tested formed precipitates. The precipitates containing all fractions (including protein AA) or protein AA plus a fraction containing a 19- and a 23-kd protein revealed congophilic green birefringent fibrillar material. Dialysis against acidic and calcium-containing solutions gave the best results. Amyloid fibril-like material was visible on electron microscopic examination. The amino acid composition of the 19 + 23-kd material appeared to be slightly different from protein AA and evidently unlike SAP. On immunofluorescence-absorbance studies the 19 + 23-kd material appeared evidently unlike protein AA and SAP. From these findings it is concluded that for spontaneous formation of AA amyloid fibrils other non-AA proteins are necessary.

Amino Acids↗
PubMed1985

Transformation of amyloid precursor SAA to protein AA and incorporation in amyloid fibrils in vivo.

Experimental amyloidosis was induced in mice by intraperitoneal injections of endotoxin (lipopolysaccharide (LPS)). In addition to LPS, a group of mice received high-density lipoprotein (HDL)-SAA complexes isolated from human acute-phase serum, whereas a group of control mice received saline in addition to LPS. Isolated amyloid fibrils from the mice given HDL-SAA contained human AA protein, as shown by immunodiffusion, immunoblot, and enzyme-linked immunosorbent assay techniques, in addition to mouse AA. In contrast, amyloid from the control mice contained exclusively AA of mouse origin. Thus, the experiments provided solid evidence that SAA is the precursor for amyloid fibril protein AA.

Amyloid↗