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β‐amyloid and tau pathology in the aging feline brain
Domestic cats (Felis catus) are known to develop cognitive impairment, and several small series have demonstrated both β‐amyloid and tau aggregation, including neurofibrillary tangles, with age, making them a promising physiologic model of Alzheimer disease (AD). We therefore report the largest feli...
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| Published in: | Journal of comparative neurology (1911) 2020-01, Vol.528 (1), p.108-113 |
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| container_title | Journal of comparative neurology (1911) |
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| creator | Fiock, Kimberly L. Smith, Jodi D. Crary, John F. Hefti, Marco M. |
| description | Domestic cats (Felis catus) are known to develop cognitive impairment, and several small series have demonstrated both β‐amyloid and tau aggregation, including neurofibrillary tangles, with age, making them a promising physiologic model of Alzheimer disease (AD). We therefore report the largest feline autopsy cohort to date of 32 cats ranging from 1.5 to 22.1 years of age, with systematic neuropathologic assessment according to NIA‐Alzheimer's Association Criteria. Formalin‐fixed paraffin‐embedded tissue sections of brain were obtained retrospectively from cats autopsied at the Iowa State College of Veterinary Medicine. We found β‐amyloid staining, predominantly in Cortical Layers IV and VI in 27 of the 32 cats used in the study, with four of these animals showing tau‐positive tangles and neuropil threads. In 75% of these cases (3/4), tau deposition was limited to entorhinal cortex, while one case showed diffuse positive staining throughout the hippocampal formation and neocortex. This last case showed positive staining for all phospho‐tau‐specific antibodies tested, similar to the pattern seen in human AD. Interestingly, we saw a higher ratio of pretangles to tangles than that in human AD, and none of the cases showed neuritic plaques on any of the stains used. Our findings indicate that aging domestic cats spontaneously develop both β‐amyloid and tau pathology similar, but not identical to that seen in human AD. This suggests that the domestic cat may serve as a potential model for mechanistic and therapeutic AD studies, but that additional research is needed to identify differences between the neuropathology of aging in humans and felines.
We looked at β‐amyloid and tau deposition in the largest published autopsy cohort of aged domestic cats (32 total animals). We found diffuse β‐amyloid staining in Cortical Layers IV and VI in 84% of the cohort overall and 96% of animals over age 14, but there was no presence of the neuritic plaques typically seen in human Alzheimer disease. Tau aggregates, including tangles, were present in the hippocampus and/or entorhinal cortex of four animals that also showed β‐amyloid pathology (14%). |
| doi_str_mv | 10.1002/cne.24741 |
| format | article |
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We looked at β‐amyloid and tau deposition in the largest published autopsy cohort of aged domestic cats (32 total animals). We found diffuse β‐amyloid staining in Cortical Layers IV and VI in 84% of the cohort overall and 96% of animals over age 14, but there was no presence of the neuritic plaques typically seen in human Alzheimer disease. Tau aggregates, including tangles, were present in the hippocampus and/or entorhinal cortex of four animals that also showed β‐amyloid pathology (14%).</description><identifier>ISSN: 0021-9967</identifier><identifier>ISSN: 1096-9861</identifier><identifier>EISSN: 1096-9861</identifier><identifier>DOI: 10.1002/cne.24741</identifier><identifier>PMID: 31273784</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Aging ; Aging - pathology ; Alzheimer disease ; Alzheimer's disease ; Amyloid beta-Peptides - analysis ; animal models ; Animals ; AT8 (RRID: AB_223647) ; Autopsy ; Brain - pathology ; Brain Chemistry ; Cats ; Cognitive ability ; Cortex (entorhinal) ; CP13 (RRID: AB_2314223) ; Hippocampus ; neurodegeneration ; Neurodegenerative diseases ; Neurofibrillary tangles ; neuropathology ; Neuropil ; Paraffin ; PHF1 (RRID: AB_2315150) ; RZ3 (RRID: AB_2716721) ; S214 (RRID: AB_1502105) ; Senile plaques ; Tau protein ; tau Proteins - analysis ; THR205 (RRID: AB_2533738) ; Uniprot (RRID: SCR_002380) ; Veterinary medicine ; β‐amyloid ; β‐amyloid (RRID: AB_2564652)</subject><ispartof>Journal of comparative neurology (1911), 2020-01, Vol.528 (1), p.108-113</ispartof><rights>2019 Wiley Periodicals, Inc.</rights><rights>2020 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4431-2e04e568319dfaad10709115b9b4790bad0daacbed1b96f656fee7a61188c68f3</citedby><cites>FETCH-LOGICAL-c4431-2e04e568319dfaad10709115b9b4790bad0daacbed1b96f656fee7a61188c68f3</cites><orcidid>0000-0002-5376-1589 ; 0000-0002-3127-4528</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcne.24741$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcne.24741$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,315,786,790,891,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31273784$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fiock, Kimberly L.</creatorcontrib><creatorcontrib>Smith, Jodi D.</creatorcontrib><creatorcontrib>Crary, John F.</creatorcontrib><creatorcontrib>Hefti, Marco M.</creatorcontrib><title>β‐amyloid and tau pathology in the aging feline brain</title><title>Journal of comparative neurology (1911)</title><addtitle>J Comp Neurol</addtitle><description>Domestic cats (Felis catus) are known to develop cognitive impairment, and several small series have demonstrated both β‐amyloid and tau aggregation, including neurofibrillary tangles, with age, making them a promising physiologic model of Alzheimer disease (AD). We therefore report the largest feline autopsy cohort to date of 32 cats ranging from 1.5 to 22.1 years of age, with systematic neuropathologic assessment according to NIA‐Alzheimer's Association Criteria. Formalin‐fixed paraffin‐embedded tissue sections of brain were obtained retrospectively from cats autopsied at the Iowa State College of Veterinary Medicine. We found β‐amyloid staining, predominantly in Cortical Layers IV and VI in 27 of the 32 cats used in the study, with four of these animals showing tau‐positive tangles and neuropil threads. In 75% of these cases (3/4), tau deposition was limited to entorhinal cortex, while one case showed diffuse positive staining throughout the hippocampal formation and neocortex. This last case showed positive staining for all phospho‐tau‐specific antibodies tested, similar to the pattern seen in human AD. Interestingly, we saw a higher ratio of pretangles to tangles than that in human AD, and none of the cases showed neuritic plaques on any of the stains used. Our findings indicate that aging domestic cats spontaneously develop both β‐amyloid and tau pathology similar, but not identical to that seen in human AD. This suggests that the domestic cat may serve as a potential model for mechanistic and therapeutic AD studies, but that additional research is needed to identify differences between the neuropathology of aging in humans and felines.
We looked at β‐amyloid and tau deposition in the largest published autopsy cohort of aged domestic cats (32 total animals). We found diffuse β‐amyloid staining in Cortical Layers IV and VI in 84% of the cohort overall and 96% of animals over age 14, but there was no presence of the neuritic plaques typically seen in human Alzheimer disease. Tau aggregates, including tangles, were present in the hippocampus and/or entorhinal cortex of four animals that also showed β‐amyloid pathology (14%).</description><subject>Aging</subject><subject>Aging - pathology</subject><subject>Alzheimer disease</subject><subject>Alzheimer's disease</subject><subject>Amyloid beta-Peptides - analysis</subject><subject>animal models</subject><subject>Animals</subject><subject>AT8 (RRID: AB_223647)</subject><subject>Autopsy</subject><subject>Brain - pathology</subject><subject>Brain Chemistry</subject><subject>Cats</subject><subject>Cognitive ability</subject><subject>Cortex (entorhinal)</subject><subject>CP13 (RRID: AB_2314223)</subject><subject>Hippocampus</subject><subject>neurodegeneration</subject><subject>Neurodegenerative diseases</subject><subject>Neurofibrillary tangles</subject><subject>neuropathology</subject><subject>Neuropil</subject><subject>Paraffin</subject><subject>PHF1 (RRID: AB_2315150)</subject><subject>RZ3 (RRID: AB_2716721)</subject><subject>S214 (RRID: AB_1502105)</subject><subject>Senile plaques</subject><subject>Tau protein</subject><subject>tau Proteins - analysis</subject><subject>THR205 (RRID: AB_2533738)</subject><subject>Uniprot (RRID: SCR_002380)</subject><subject>Veterinary medicine</subject><subject>β‐amyloid</subject><subject>β‐amyloid (RRID: AB_2564652)</subject><issn>0021-9967</issn><issn>1096-9861</issn><issn>1096-9861</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp1kU1OHDEQRi1EBBNgwQVQS2zIosHldrvtDVI0moRICDawtqq7q2eMeuxJ_wTNLkfIWTgIh8hJYjIEESRWtainp6_qY-wQ-ClwLs4qT6dCFhK22AS4UanRCrbZJO4gNUYVu-xj399xzo3J9A7bzUAUWaHlhOnHh98_f-Fy3QZXJ-jrZMAxWeGwCG2YrxPnk2FBCc6dnycNtc5TUnbo_D770GDb08Hz3GO3X2Y304v08vrrt-nny7SSMoNUEJeUK52BqRvEGnjBDUBemlIWhpdY8xqxKqmG0qhG5aohKlABaF0p3WR77HzjXY3lkuqK_NBha1edW2K3tgGd_X_j3cLOww-rtBTA8yg4eRZ04ftI_WCXrq-obdFTGHsrRJ4JrYpcR_T4DXoXxs7H86yIL5MmyxVE6tOGqrrQ9x01L2GA26c-bOzD_u0jskev07-Q_wqIwNkGuHctrd832enVbKP8AyI0lZE</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Fiock, Kimberly L.</creator><creator>Smith, Jodi D.</creator><creator>Crary, John F.</creator><creator>Hefti, Marco M.</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QR</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5376-1589</orcidid><orcidid>https://orcid.org/0000-0002-3127-4528</orcidid></search><sort><creationdate>20200101</creationdate><title>β‐amyloid and tau pathology in the aging feline brain</title><author>Fiock, Kimberly L. ; Smith, Jodi D. ; Crary, John F. ; Hefti, Marco M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4431-2e04e568319dfaad10709115b9b4790bad0daacbed1b96f656fee7a61188c68f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aging</topic><topic>Aging - pathology</topic><topic>Alzheimer disease</topic><topic>Alzheimer's disease</topic><topic>Amyloid beta-Peptides - analysis</topic><topic>animal models</topic><topic>Animals</topic><topic>AT8 (RRID: AB_223647)</topic><topic>Autopsy</topic><topic>Brain - pathology</topic><topic>Brain Chemistry</topic><topic>Cats</topic><topic>Cognitive ability</topic><topic>Cortex (entorhinal)</topic><topic>CP13 (RRID: AB_2314223)</topic><topic>Hippocampus</topic><topic>neurodegeneration</topic><topic>Neurodegenerative diseases</topic><topic>Neurofibrillary tangles</topic><topic>neuropathology</topic><topic>Neuropil</topic><topic>Paraffin</topic><topic>PHF1 (RRID: AB_2315150)</topic><topic>RZ3 (RRID: AB_2716721)</topic><topic>S214 (RRID: AB_1502105)</topic><topic>Senile plaques</topic><topic>Tau protein</topic><topic>tau Proteins - analysis</topic><topic>THR205 (RRID: AB_2533738)</topic><topic>Uniprot (RRID: SCR_002380)</topic><topic>Veterinary medicine</topic><topic>β‐amyloid</topic><topic>β‐amyloid (RRID: AB_2564652)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fiock, Kimberly L.</creatorcontrib><creatorcontrib>Smith, Jodi D.</creatorcontrib><creatorcontrib>Crary, John F.</creatorcontrib><creatorcontrib>Hefti, Marco M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of comparative neurology (1911)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fiock, Kimberly L.</au><au>Smith, Jodi D.</au><au>Crary, John F.</au><au>Hefti, Marco M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>β‐amyloid and tau pathology in the aging feline brain</atitle><jtitle>Journal of comparative neurology (1911)</jtitle><addtitle>J Comp Neurol</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>528</volume><issue>1</issue><spage>108</spage><epage>113</epage><pages>108-113</pages><issn>0021-9967</issn><issn>1096-9861</issn><eissn>1096-9861</eissn><notes>Funding information</notes><notes>National Institutes of Health, Grant/Award Numbers: R01AG054008, R01NS095252, UL1TR002537; U.S. Department of Defense, Grant/Award Number: 13267017; Alexander Saint‐Amand Scholarship; Tau Consortium</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>Domestic cats (Felis catus) are known to develop cognitive impairment, and several small series have demonstrated both β‐amyloid and tau aggregation, including neurofibrillary tangles, with age, making them a promising physiologic model of Alzheimer disease (AD). We therefore report the largest feline autopsy cohort to date of 32 cats ranging from 1.5 to 22.1 years of age, with systematic neuropathologic assessment according to NIA‐Alzheimer's Association Criteria. Formalin‐fixed paraffin‐embedded tissue sections of brain were obtained retrospectively from cats autopsied at the Iowa State College of Veterinary Medicine. We found β‐amyloid staining, predominantly in Cortical Layers IV and VI in 27 of the 32 cats used in the study, with four of these animals showing tau‐positive tangles and neuropil threads. In 75% of these cases (3/4), tau deposition was limited to entorhinal cortex, while one case showed diffuse positive staining throughout the hippocampal formation and neocortex. This last case showed positive staining for all phospho‐tau‐specific antibodies tested, similar to the pattern seen in human AD. Interestingly, we saw a higher ratio of pretangles to tangles than that in human AD, and none of the cases showed neuritic plaques on any of the stains used. Our findings indicate that aging domestic cats spontaneously develop both β‐amyloid and tau pathology similar, but not identical to that seen in human AD. This suggests that the domestic cat may serve as a potential model for mechanistic and therapeutic AD studies, but that additional research is needed to identify differences between the neuropathology of aging in humans and felines.
We looked at β‐amyloid and tau deposition in the largest published autopsy cohort of aged domestic cats (32 total animals). We found diffuse β‐amyloid staining in Cortical Layers IV and VI in 84% of the cohort overall and 96% of animals over age 14, but there was no presence of the neuritic plaques typically seen in human Alzheimer disease. Tau aggregates, including tangles, were present in the hippocampus and/or entorhinal cortex of four animals that also showed β‐amyloid pathology (14%).</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>31273784</pmid><doi>10.1002/cne.24741</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-5376-1589</orcidid><orcidid>https://orcid.org/0000-0002-3127-4528</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Aging Aging - pathology Alzheimer disease Alzheimer's disease Amyloid beta-Peptides - analysis animal models Animals AT8 (RRID: AB_223647) Autopsy Brain - pathology Brain Chemistry Cats Cognitive ability Cortex (entorhinal) CP13 (RRID: AB_2314223) Hippocampus neurodegeneration Neurodegenerative diseases Neurofibrillary tangles neuropathology Neuropil Paraffin PHF1 (RRID: AB_2315150) RZ3 (RRID: AB_2716721) S214 (RRID: AB_1502105) Senile plaques Tau protein tau Proteins - analysis THR205 (RRID: AB_2533738) Uniprot (RRID: SCR_002380) Veterinary medicine β‐amyloid β‐amyloid (RRID: AB_2564652) |
| title | β‐amyloid and tau pathology in the aging feline brain |
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