Amyloid Substance Research Articles

Senile cardiac amyloidosis

A case of senile cardiac amyloidosis with recurrent episodes of congestive heart failure is reported here. An 83‐year‐old woman with a history of hypertension was admitted for the treatment of worsening dyspnea. The echocardiography revealed diffuse mild hypokinesis of the left ventricle with an ejection fraction of 46%. An elevated E wave and shortened deceleration time in the left ventricular inflow waveform was demonstrated with Doppler echocardiography, which suggested that the nature of the heart failure was restrictive. The patient required hospitalization for the treatment of congestive heart failure four times in 2 years. An autopsy revealed deposition of prealbumin‐positive amyloid substance in the atrial myocardium and the intramyocardial arterioles of the left ventricle. Recurrent congestive heart failure was presumed to be a result of diastolic dysfunction due to senile cardiac amyloidosis.

Amiloidosis vesical primaria

AbstractPrimary amyloidosis of the bladder is a rare disease entity manifested as extracellular deposits of a fibril protein in an amyloid substance formClinical presentation resembles a bladder tumor, as hematuria is the most common clinical manifestationSingle organ affectation is most frecuent in the bladder, however, we have found less than 100 casesWe present the case of a woman with primary amyloidosis of the urinary bladder with simptoms of hematuria. Endoscopic examination suggested a bladder tumor

Vascular and parenchymal Aβ deposition in the aging dog: correlation with behavior

The behavior of 25 dogs was indirectly assessed by a formal questionnaire (evaluation of Age-Related Cognitive and Affective Disorders—ARCAD), filled out by the owner. The density of diffuse and vascular deposits was evaluated using four anti-Aβ peptide antibodies, in four temporal areas. Parenchymal, diffuse deposits of Aβ42 peptide were found in all aged animals but one. They were Congo red negative and were not immunostained by the anti-Aβ40 antibody, contrary to the vascular deposits. The densities of vascular and parenchymal deposits were not correlated. The ARCAD score was correlated with age, density of Aβ parenchymal and vascular deposits, and with the number of areas containing deposits (extension index). Multivariate analysis showed that the age and the extension index explained most of the variance. Congo red positivity (indicating that the Aβ peptide has the characteristics of an amyloid substance) is limited in the dog to the vascular wall and is associated, as in man, with the deposition of the Aβ 1–40 isoform. Parenchymal Aβ deposition seems to be a common correlate of behavioral problems in aging dogs.

Mécanismes de l'amylose et protéines impliquées

Recent data in amyloid research have shed light on the amyloid substance and have broadened our knowledge on the mechanism of amyloid deposition. Despite uniform physical properties relating to the presence of beta-pleates, amyloid deposits are chemically heterogeneous and have different origins; additional types will probably be described in the future. Immunohistochemical techniques using specific antisera for each of the major protein present in fibrils could help greatly to subclassify these disorders. In most circumstances, a circulating precursor protein may result from overproduction of either intact or aberrant molecule, a reduction in its degradation or excretion, or genetic abnormalities associated with variant proteins. The cleavage of protein precursor molecules of the protein component of amyloid fibrils characterizes amyloidogenesis, though it is not necessary for some amyloidosis forms. This review summarizes advances in the understanding of the nature of amyloid substances, the mechanism of amyloid deposition and the principal pathogenic hypothesis. SAP component is common in all amyloidosis and may be the target for future therapy.

Are vascular factors involved in Alzheimer's disease? Facts and theories.

The hypothesis that vascular factors may contribute to the development of Alzheimer's disease (AD) is supported by epidemiologic and pathologic observations. Arterial hypertension and diabetes have been found to be associated not only with vascular dementia, but also with AD; in addition, the treatment of hypertension with calcium antagonists seems to prevent degenerative dementias. Hypertension and hyperinsulinemia favor the deposition of amyloid substance in the brain. The histopathology of AD is marked not only by neurofibrillary tangles and senile plaques, but also by macro and micro congophilic angiopathy and ischemic white matter rarefaction. The specific AD pathological lesions, if isolated, are not able to lead to an evident clinical picture of dementia, which, on the contrary, becomes evident when vascular, mainly subcortical, lesions are associated. These and other observations suggest that vascular factors may have a role in the development of AD. An aggressive approach to these factors could be of value in the prevention of AD.

Comparison of the Structures of β Amyloid Peptide (25–35) and Substance P in Trifluoroethanol/Water Solution

The three-dimensional structure of β amyloid peptide (25–35) in aqueous solution with 50% (vol/vol) 2,2,2-trifluoroethanol was determined by NMR spectroscopy, β Amyloid pep- tide(Aβ) is the major component of senile plaques found in the brain of patient of Alzheimer's disease. Aβ25-35 is biologically active fragment of Aβ and exhibits some sequence homology with the tachykinin family. In this study, we present the structural similarity between Aβ25-35 and substance P which is a member of tachykinin family in order to examine the possibility of sharing pathways mediated by tachykinin receptors. Both peptides have a-helical structures in their C-terminal regions and aromatic rings or hydrophobic side chains in the center of the helix protrude outside. These conformational features are expected to be the key for the interaction with the receptors.

Fourier transform infrared spectroscopic investigation of temperature- and pressure-induced disaggregation of amyloid A.

The conformation-sensitive amide I band in the Fourier transform infrared (FTIR) spectra of amyloid A suspensions in D2O was examined as a function of temperature (25-95 degrees C) and applied hydrostatic pressure (1-12 kbar) to assess the stability of the peptide. The principal changes observed upon heating were a significant loss of intermolecular beta-sheet structure, and an increase in the broad band centred at 1644 cm(-1) assigned to unordered structure and alpha-helices of the dissociated species. Application of hydrostatic pressure at ambient temperature resulted in a limited degree of aggregate dissociation. These structural changes were partially reversible with cooling or release of the applied pressure. Dissolving the aggregated peptide in alkaline solution (pH 12) also resulted in disaggregation. Dissociation of organ-deposited amyloid substance bears clinical relevance. The present data indicate that residual amounts of undissociated amyloid in the milieu at physiological and acidic pH may act as nucleating foci rendering dissociated amyloid to reaggregate into organized amyloid.

Familial amyloid polyneuropathy type I (Portuguese): Distribution and characterization of renal amyloid deposits

Renal amyloidosis has been considered rare and late in the evolution of the transthyretin (TTR) familial amyloid polyneuropathy (FAP) of the Portuguese type (type I). Renal biopsy has been performed systematically in 14 patients with FAP type I before liver transplantation. In all patients, TTR Met30 mutation was shown. Seven had proteinuria or abnormal microalbuminuria, whereas seven others had no urinary abnormalities. All had renal amyloid deposition predominantly in the medulla. Glomerular and vascular involvement was more prominent in patients with urinary abnormalities. Patients with the most extensive renal lesions represented a subgroup with a low score of polyneuropathy disability, a high prevalence of nephropathy in the proband generation, or a late onset for relatives with nephropathy. Immunohistochemistry studies showed that the amyloid substance corresponded to transthyretin. We have shown that renal TTR-derived amyloid deposition is common in patients with FAP type I, even in the absence of urinary abnormalities. The clinical presentation of nephropathy is not a late occurrence in the disease. (Am J Kidney Dis 1998 Jun;31(6):940-6)

Systemic Amyloidosis in Laying Japanese Quail

Systemic amyloidosis was seen in laying Japanese quail in a flock of a farm rearing 95,000 birds. The clinical signs included decreased egg production, anorexia, white diarrhea, and subcutaneous abscesses of the head. Histologically, amyloid deposited predominantly in the spleen and liver. In addition, there were lesser degrees of amyloidosis in other organs (pancreas, kidney, heart, lung, gastrointestinal tract). Amyloid stained positively with Congo red and thioflavin T. Immunohistochemically, amyloid substance stained positively against amyloid A protein, but not with amyloid protein derived from light chains of immunoglobulins, transthyretin of familiar amyloid polyneuropathy, amyloid protein of dermal amyloidosis, nor amyloid P component. Ultrastructurally, amyloid substance consisted of many nonbranching amyloid fibrils about 10 nm in diameter.

The progression of the lesions in Alzheimer disease: insights from a prospective clinicopathological study.

Senile plaques and neurofibrillary tangles are the markers of Alzheimer's disease. They are also found in old patients who have been considered to be intellectually normal throughout their life, a situation referred to as "physiological aging". The neurofibrillary tangles are made of abnormally phosphorylated tau. The anti-tau antibody labels not only the neurofibrillary tangles, but also the crown of the senile plaques and the neuropil threads interspersed between the cell bodies and the plaques. The senile plaque comprises a core made of A beta peptide surrounded by a neuritic crown. The anti-A beta antibody also labels "diffuse deposits", i.e. ill limited areas of immunoreactivity which lacks the characteristics of the amyloid substance. The intellectual deficit appears to be statistically linked with the density of the tau-positive alterations-tangles, threads and plaque crowns--which usually appear simultaneously in a given cortical area. In the entorhinal area, their density increases proportionally to the intellectual deficit without threshold, suggesting that ageing and disease are a continuum. In the isocortex, the progression of the tau positive alterations is, on the contrary, stepwise--in a "all or none" fashion--from the hippocampus to the primary cortices, through the associative multimodal areas. The tau positive lesions probably progress through connections: they indeed disappear from areas, that have been disconnected by additional lesions (such as infarcts).

Primary Systemic Amyloidosis

Background: Primary systemic amyloidosis is a rare disease with multiorgan involvement including the skin. Because of the nonspecific and variable presenting symptoms and signs, this condition usually follows a long course before the correct diagnosis is established. Fortunately, skin manifestations contribute greatly in revealing the disease and determining the amyloidosis type. Objective: This article reports a case of primary systemic amyloidosis mimicking nodular primary localized cutaneous amyloidosis of the legs. We describe our systemic findings and the investigation procedure to classify and characterize the amyloidosis type. Methods and Results: After histologic studies revealed amyloid substance in the skin nodules of our 82-year-old patient, she was hospitalized for an appropriate systemic evaluation of this condition and associated medical problems. The investigation included biochemical, immunologic, radiologic, pathologic, and histochemical methods. Conclusion: This case of primary systemic amyloidosis, simulating a localized cutaneous form with nodular lesions, demonstrates the importance of the distinction between both entities. In fact, the management and prognosis will vary significantly.

Ocular Amyloidosis, With Special Reference to the Hereditary Forms With Vitreous Involvement

The complex of diseases referred to as amyloidosis is characterized by the deposition of amyloid substance in various tissues. The amyloid protein differs in the various forms of amyloidosis. This variation is the basis of the differences in affected tissues and subsequent clinical dissimilarities. Vitreous involvement in amyloidosis seems to be especially linked to some of the hereditary neuropathies associated with the amyloid protein transthyretin. Characterization of the amyloid proteins during recent decades has allowed a chemical and immunologic classification of amyloid fibrils. This paper presents the basis for classification of amyloidosis, reviews the literature on ocular amyloidosis, with special reference to vitreous involvement, and summarizes clinical findings and frequency of vitreous amyloid involvement in Swedish patients with familial amyloidotic polyneuropathy.

Malignant lymphoma of mucosa associated lymphoid tissue: a new etiology of amyloidosis

Non Hodgkin Malignant lymphomas (NHML) of mucosa associated lymphoid tissue (MALT) are known to have multiple involvement of the digestive tract. We report one case, presenting with an infiltrative process of the jejuno-ileum, associating lymphoplasmacytoid proliferating cells and amyloidosis. The plasmacytoid cells expressed Alpha and scarce Mu heavy chains, and lambda light chain. Lympho-epithelial lesions were more obvious at the second site of involvement, in the gastric mucosa. The amyloid substance was negative with the Amyloid A component antibody and gave a background noise with Alpha, Mu and lambda chains. No similar report of amyloidosis associated with MALT NHML has been found in the literature.

Occupational and Other Risk Factors for Clinically Overt Familial Amyloid Polyneuropathy

Amyloidosis is associated with the deposition of amyloid substance in various tissues of the body. In several forms of familial amyloid polyneuropathy, mutated transthyretin is the main fibril component. The disease is inherited as an autosomal dominant trait with onset in adult life, but few carriers develop symptoms. The aim of the present investigation was to screen for additional factors that might be necessary for the development of familial amyloid polyneuropathy. We conducted a case-control study involving 51 male and 30 female cases of clinically overt familial amyloid polyneuropathy and 306 male and 317 female population controls. We considered occupational exposures, disease histories, and medical treatments as potential determinants of risk for clinically overt disease. We found an odds ratio of 5.4 for dressmakers. Low and high levels of exposure to organic solvents resulted in an odds ratio of 2.1 and 11.8, respectively. A history of prostatic hyperplasia, cholecystic disease, or appendectomy was also a risk factor, possibly as a consequence of anesthesia.

Pleural amyloidosis: thoracoscopic aspects

We describe the case of a 60 year old man with primary amyloidosis, who suffered from peripheral neuropathy and cardiomyopathy and who presented with recurrent right pleural effusion. For this reason, he was admitted to hospital for thoracoscopic examination with pleurodesis. Macroscopic examination of the parietal pleura revealed a diffuse inflammation and light brown deposits that where covered with nodules. Biopsy specimens confirmed the amyloid deposition. This macroscopic appearance is described for the first time, and suggests that a local pleural synthesis of amyloid substance may occur during the course of systemic amyloidosis.

Comparison of Pulmonary Ga-67 and Tc-99m MAA Imaging in a Patient With Primary Amyloidosis

Scintigraphic images with Ga-67 accumulated in amyloid substance in a sensitive, but nonspecific way. On the contrary, Tc-99m MAA is able to show hypoperfusion resulting from mechanical damage. The authors describe a case of pulmonary amyloidosis in a patient with primary amyloidosis with accumulation of Ga-67 in the areas where Tc-99m MAA shows strongly hypoactive areas

Amyloid in basal cell carcinoma and seborrheic keratosis.

The frequency of amyloid substance was studied in two different types of skin tumours: basal cell carcinoma and seborrheic keratosis. In 9 out of 49 cases of seborrheic keratosis amyloid substance was found. In the basal cell carcinomas, 194 out of 260 cases showed amyloid deposits, a rate that is higher than that previously reported. The basal cell carcinoma material was further studied regarding the amount of amyloid, mitotic rate, degree of apoptosis and the age of the patients. There was no correlation between the amount of amyloid and the mitotic rate, or the degree of apoptosis. There was a slightly higher incidence of amyloid-positive cases among elderly patients.

NMDA activation increases tau phosphorylation in primary neuronal cultures: an immunoblot study : M. Lesort, P. Couratier, F. Esclaire, P. Sindou, J. Hugon Unité de Neurobiologie Cellulaire, Lab. d'Histologie - Faculté de Médecine, 2 rue du Dr Marcland 87025 LIMOGES cédex FRANCE

Degenerating neurofibrils (DNF), which are composed of paired helical filaments (PHF) and amyloid fibrils (AF), are the 2 characteristic pathological fibrillar deposits in Alzheimer cortex. These fibrils were simultaneously studied by 2 techniques: The immunolabelling with a specific antiserum raised against PHF and elective thioflavine S staining of AF.In neuronal perikaryons, neurofibrillary tangles (NFT) consist of 3 populations: firstly, strongly immunolabelled tangles were weakly thioflavine-stained. Secondly, less dense tangles were weakly immunolabelled but strongly thioflavine-stained. Thirdly, ghost tangles which correspond to extracellular NFT were exclusively thioflavine-stained. Thus, it is likely that NFT are degraded to form extracellular AF.Around neuritic plaques and some vessels with amyloid angiopathy, immunolabelled neurites, thioflavine-stained neurites and transition figures were also observed. On the other hand, the central core of plaques and pathological vessel walls were strongly thioflavine-stained but were never immunoreactive.In conclusion, these observations favour catabolism of PHF bundles found in NFT and in degenerating neurites into an amyloid substance. This amyloid substance seems different from other amyloid deposits found in the central core of neuritic plaques and vessel walls.

Peripheral markers and diagnostic criteria in Alzheimer's disease: critical evaluations.

This review analyzes recent developments in diagnostic criteria and peripheral markers used clinically in the definitive diagnosis of Alzheimer's disease (AD), comparing past and current views, together with a discussion of their shortcoming and difficulties of implementation. Consideration is given to studies on the presence of amyloid substances outside the central nervous system: in cerebrospinal fluid, in plasma, in primary cultures, and in continuous cultures of cell lines of neuronal and glial origin. We discuss alterations of cholinesterases and noradrenaline in red blood cells (RBC) in AD and, with relation to the infectious theory, the presence of spirochaetes in patients. The activities of the enzymes leading to the formation of amyloid substances and those reflecting more general alterations of metabolic processes are considered, both in respect to their role in the pathogenesis of the neurodegenerative disorders of AD and of their potential use as markers. Enzymatic changes have been studied comparing AD patients with non AD controls as well as with AD relatives: proteases and their inhibitors; plasminogen activators; transketolases; increases in the activity of Cu-Zn superoxide dismutase in AD patients' RBC, serum, fibroblasts and cortical neurons, pointing to alterations in oxidative processes; and apolipoprotein E epsilon 4 allele, linked to late-onset AD and familial cases. This review presents reasons why the involvement of peripheral markers in AD should advance from hypothesis to accepted fact.

Alzheimer's disease-like dystrophic neurites characteristically associated with senile plaques are not found within other neurodegenerative disease unless amyloid β-protein deposition is present

Swollen, bulbous-shaped (dystrophic) neurites are a common pathologic feature of Alzheimer's disease (AD) and represent one of the most abundant neuritic abnormalities within the brains of patients with this disease. In the present study, we sought to determine whether the dystrophic neurites which are observed in association with senile plaques are unique to AD or whether they are characteristic of a more generalized process of neuritic and/or neuronal degeneration which can be observed in other neurodegenerative diseases. To accomplish this, we examined post-mortem brain material from patients with AD, Parkinson's disease (PD), Parkinson's disease with associated AD, Parkinson's disease with dementia yet without AD pathology, Huntington's disease (HD), Pick's disease and normal age-matched controls (NC). Using a battery of antibodies to amyloid β-protein (AβP), paired-helical filaments (PHF), tyrosine hydroxylase, substance P, neurotensin, and somatostatin we found that immunolabeled dystrophic neurites of the type characteristically observed in AD, were seen only in cases and in brain regions where AβP deposition was present. More specifically, brain areas known to display severe afferent and/or local degenerative changes such as the caudate and putamen in all three PD groups, the caudate in the HD cases, and the temporal cortex in the HD and Pick's cases were conspicuously free of these swollen neurites unless AβP deposition was also present. While these findings did not exclude the possibility that other forms of neuritic degeneration may accompany the degeneration seen in these other diseases, they do suggest that the enlarged immunolabeled neurites so frequently observed in AD brains are unique to AD and in particular are restricted to brain regions with β-amyloid deposits.