AA-amyloidosis in cats (<i>Felis catus</i>) housed in shelters

Ferri, Filippo; Ferro, Silvia; Porporato, Federico; Callegari, Carolina; Guglielmetti, Chiara; Mazza, Maria; Ferrero, Marta; Crinò, Chiara; Gallo, Enrico; Drigo, Michele; Coppola, Luigi; Gerardi, Gabriele; Schulte, Tim; Ricagno, Stéfano; Vogel, Monique; Storni, Federico; Bachmann, Martin F.; Vogt, Anne-Cathrine S.; Caminito, Serena; Mazzini, Giulia; Lavatelli, Francesca; Palladini, Giovanni; Merlini, Giampaolo; Zini, Eric

doi:10.1101/2022.05.04.490646

Cited by 4 publications

(16 citation statements)

References 25 publications

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“…Full details were described previously 47 . In brief, organs were collected within 5 h from death, fixed in 10% formalin, and embedded in paraffin.…”

Section: Methodsmentioning

confidence: 99%

“…A prion-like spread of AA amyloidosis was also inferred from studies in which parenteral administered amyloid accelerated deposition in inflamed animals 2,45,46 . Our recent study has revealed a prevalence of 57-73% among 80 domestic short hair (DSH) cats kept in shelters 47 , in stark contrast to a very low prevalence (1-2 %) in client-owned cats 48–51 .…”

Section: Introductionmentioning

confidence: 97%

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Cryo-EM structure ofex vivofibrils associated with extreme AA amyloidosis prevalence in a cat shelter

Schulte

Chaves-Sanjuán

Mazzini

et al. 2022

Preprint

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AA amyloidosis is a systemic disease characterized by deposition of misfolded serum amyloid A protein (SAA) into cross-β amyloid in multiple organs in humans and animals. AA amyloidosis occurs at high SAA serum levels during chronic inflammation. The disease can be transmitted horizontally, likely facilitated by prion-like mechanism, in captive animals leading to extreme disease prevalence, e.g. 70% in captive cheetah and 57-73% in domestic short hair (DSH) cats kept in shelters.Herein, we present the 3.3 Å cryo-EM structure of an AA amyloid extracted post-mortem from the kidney of a DSH cat with renal failure. The structure reveals a cross-β architecture assembled from two 76-residue long proto-filaments. Despite >70% sequence homology to mouse and human SAA, the cat SAA variant adopts a distinct amyloid fold. Based on shared disease profiles and almost identical protein sequences, we propose a similar amyloid fold of deposits identified previously in captive cheetah.

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“…Full details were described previously 47 . In brief, organs were collected within 5 h from death, fixed in 10% formalin, and embedded in paraffin.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Cryo-EM structure ofex vivofibrils associated with extreme AA amyloidosis prevalence in a cat shelter

Schulte

Chaves-Sanjuán

Mazzini

et al. 2022

Preprint

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“…Importantly, SAA has been suggested as prion candidate, based on extreme disease prevalence in captive cheetah and experimentally accelerated AA amyloidosis in chronically inflamed animals after intravenous injection or oral administration of amyloid 2,48,50,51 . Our recent study has revealed a prevalence of 57-73% among 80 domestic short hair (DSH) cats kept in shelters 52 , in stark contrast to a very low prevalence (1-2%) in clientowned cats 53,54 . AA amyloid deposits were found in the kidney, liver, spleen, and even the heart 52 .…”

mentioning

confidence: 97%

“…Our recent study has revealed a prevalence of 57-73% among 80 domestic short hair (DSH) cats kept in shelters 52 , in stark contrast to a very low prevalence (1-2%) in clientowned cats 53,54 . AA amyloid deposits were found in the kidney, liver, spleen, and even the heart 52 . SAA was present in cat bile, indicating a potential fecal-oral transmission route, as reported for captive cheetah 39,52 .…”

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confidence: 97%

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Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter

et al. 2022

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AA amyloidosis is a systemic disease characterized by deposition of misfolded serum amyloid A protein (SAA) into cross-β amyloid in multiple organs in humans and animals. AA amyloidosis occurs at high SAA serum levels during chronic inflammation. Prion-like transmission was reported as possible cause of extreme AA amyloidosis prevalence in captive animals, e.g. 70% in cheetah and 57–73% in domestic short hair (DSH) cats kept in zoos and shelters, respectively. Herein, we present the 3.3 Å cryo-EM structure of AA amyloid extracted post-mortem from the kidney of a DSH cat with renal failure, deceased in a shelter with extreme disease prevalence. The structure reveals a cross-β architecture assembled from two 76-residue long proto-filaments. Despite >70% sequence homology to mouse and human SAA, the cat SAA variant adopts a distinct amyloid fold. Inclusion of an eight-residue insert unique to feline SAA contributes to increased amyloid stability. The presented feline AA amyloid structure is fully compatible with the 99% identical amino acid sequence of amyloid fragments of captive cheetah.

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Renal amyloid‐A amyloidosis in cats: Characterization of proteinuria and biomarker discovery, and associations with kidney histology

Palizzotto,

Ferri,

Callegari

et al. 2023

Veterinary Internal Medicne

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BackgroundAmyloid A (AA) amyloidosis is a protein misfolding disease arising from serum amyloid A (SAA). Systemic AA amyloidosis recently was shown to have a high prevalence in shelter cats in Italy and was associated with azotemia and proteinuria.ObjectivesInvestigate urine protein profiles and diagnostic biomarkers in cats with renal AA amyloidosis.AnimalsTwenty‐nine shelter cats.MethodsCase‐control study. Cats with renal proteinuria that died or were euthanized between 2018 and 2021 with available necropsy kidney, liver and spleen samples, and with surplus urine collected within 30 days before death, were included. Histology was used to characterize renal damage and amyloid amount and distribution; immunohistochemistry was used to confirm AA amyloidosis. Urine protein‐to‐creatinine (UPC) and urine amyloid A‐to‐creatinine (UAAC) ratios were calculated, and sodium dodecyl sulfate‐agarose gel electrophoresis (SDS‐AGE) and liquid chromatography‐mass spectrometry (LC‐MS) of proteins were performed.ResultsTwenty‐nine cats were included. Nineteen had AA amyloidosis with renal involvement. Cats with AA amyloidosis had a higher UPC (median, 3.9; range, 0.6‐12.7 vs 1.5; 0.6‐3.1; P = .03) and UAAC ratios (median, 7.18 × 10−3; range, 23 × 10−3‐21.29 × 10−3 vs 1.26 × 10−3; 0.21 × 10−3‐6.33 × 10−3; P = .04) than unaffected cats. The SDS‐AGE identified mixed‐type proteinuria in 89.4% of cats with AA amyloidosis and in 55.6% without AA amyloidosis (P = .57). The LC‐MS identified 63 potential biomarkers associated with AA amyloidosis (P < .05). Among these, urine apolipoprotein C‐III was higher in cats with AA amyloidosis (median, 1.38 × 107; range, 1.85 × 105‐5.29 × 107 vs 1.76 × 106; 0.0 × 100‐1.38 × 107; P = .01). In the kidney, AA‐amyloidosis was associated with glomerulosclerosis (P = .02) and interstitial fibrosis (P = .05).Conclusions and Clinical ImportanceRenal AA amyloidosis is associated with kidney lesions, increased proteinuria and increased urine excretion of SAA in shelter cats. Additional studies are needed to characterize the role of lipid transport proteins in the urine of affected cats.

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AA-amyloidosis in cats (Felis catus) housed in shelters

Cited by 4 publications

References 25 publications

Cryo-EM structure ofex vivofibrils associated with extreme AA amyloidosis prevalence in a cat shelter

Cryo-EM structure ofex vivofibrils associated with extreme AA amyloidosis prevalence in a cat shelter

Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter

Renal amyloid‐A amyloidosis in cats: Characterization of proteinuria and biomarker discovery, and associations with kidney histology

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