The microvascular extracellular matrix in brains with Alzheimer’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA)
Abstract Background The microvasculature (MV) of brains with Alzheimer’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA), in the absence of concurrent pathologies (e.g., infarctions, Lewy bodies), is incompletely understood. Objective To analyze microvascular density, dia...
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | Fluids and Barriers of the CNS |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12987-020-00219-y |
| _version_ | 1818655091307053056 |
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| author | Mamatha Damodarasamy Robert B. Vernon Jasmine L. Pathan C. Dirk Keene Anthony J. Day William A. Banks May J. Reed |
| author_facet | Mamatha Damodarasamy Robert B. Vernon Jasmine L. Pathan C. Dirk Keene Anthony J. Day William A. Banks May J. Reed |
| author_sort | Mamatha Damodarasamy |
| collection | DOAJ |
| description | Abstract Background The microvasculature (MV) of brains with Alzheimer’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA), in the absence of concurrent pathologies (e.g., infarctions, Lewy bodies), is incompletely understood. Objective To analyze microvascular density, diameter and extracellular matrix (ECM) content in association with ADNC and CAA. Methods We examined samples of cerebral cortex and isolated brain microvasculature (MV) from subjects with the National Institute on Aging-Alzheimer's Association (NIA-AA) designations of not-, intermediate-, or high ADNC and from subjects with no CAA and moderate-severe CAA. Cases for all groups were selected with no major (territorial) strokes, ≤ 1 microinfarct in screening sections, and no Lewy body pathology. MV density and diameter were measured from cortical brain sections. Levels of basement membrane (BM) ECM components, the protein product of TNF-stimulated gene-6 (TSG-6), and the ubiquitous glycosaminoglycan hyaluronan (HA) were assayed by western blots or HA ELISA of MV lysates. Results We found no significant changes in MV density or diameter among any of the groups. Levels of BM laminin and collagen IV (col IV) were lower in MV isolated from the high ADNC vs. not-ADNC groups. In contrast, BM laminin was significantly higher in MV from the moderate-severe CAA vs. the no CAA groups. TSG-6 and HA content were higher in the presence of both high ADNC and CAA, whereas levels of BM fibronectin and perlecan were similar among all groups. Conclusions Cortical MV density and diameter are not appreciably altered by ADNC or CAA. TSG-6 and HA are increased in both ADNC and CAA, with laminin and col IV decreased in the BM of high ADNC, but laminin increased in moderate-severe CAA. These results show that changes in the ECM occur in AD and CAA, but independently of one another, and likely reflect on the regional functioning of the brain microvasculature. |
| first_indexed | 2024-12-17T03:04:10Z |
| format | Article |
| id | doaj.art-c66b7e64f460440c89286a7d1bbfc0d8 |
| institution | Directory Open Access Journal |
| issn | 2045-8118 |
| language | English |
| last_indexed | 2024-12-17T03:04:10Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Fluids and Barriers of the CNS |
| spelling | doaj.art-c66b7e64f460440c89286a7d1bbfc0d82022-12-21T22:06:00ZengBMCFluids and Barriers of the CNS2045-81182020-09-0117111110.1186/s12987-020-00219-yThe microvascular extracellular matrix in brains with Alzheimer’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA)Mamatha Damodarasamy0Robert B. Vernon1Jasmine L. Pathan2C. Dirk Keene3Anthony J. Day4William A. Banks5May J. Reed6Division of Gerontology and Geriatric Medicine, Department of Medicine, University of WashingtonMatrix Biology Program, Benaroya Research Institute at Virginia MasonDivision of Gerontology and Geriatric Medicine, Department of Medicine, University of WashingtonDivision of Neuropathology, Department of Pathology, University of WashingtonWellcome Trust Centre for Cell-Matrix Research and Lydia Becker Institute of Immunology and Inflammation, Division of Cell-Matrix Biology & Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Sciences CentreDivision of Gerontology and Geriatric Medicine, Department of Medicine, University of WashingtonDivision of Gerontology and Geriatric Medicine, Department of Medicine, University of WashingtonAbstract Background The microvasculature (MV) of brains with Alzheimer’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA), in the absence of concurrent pathologies (e.g., infarctions, Lewy bodies), is incompletely understood. Objective To analyze microvascular density, diameter and extracellular matrix (ECM) content in association with ADNC and CAA. Methods We examined samples of cerebral cortex and isolated brain microvasculature (MV) from subjects with the National Institute on Aging-Alzheimer's Association (NIA-AA) designations of not-, intermediate-, or high ADNC and from subjects with no CAA and moderate-severe CAA. Cases for all groups were selected with no major (territorial) strokes, ≤ 1 microinfarct in screening sections, and no Lewy body pathology. MV density and diameter were measured from cortical brain sections. Levels of basement membrane (BM) ECM components, the protein product of TNF-stimulated gene-6 (TSG-6), and the ubiquitous glycosaminoglycan hyaluronan (HA) were assayed by western blots or HA ELISA of MV lysates. Results We found no significant changes in MV density or diameter among any of the groups. Levels of BM laminin and collagen IV (col IV) were lower in MV isolated from the high ADNC vs. not-ADNC groups. In contrast, BM laminin was significantly higher in MV from the moderate-severe CAA vs. the no CAA groups. TSG-6 and HA content were higher in the presence of both high ADNC and CAA, whereas levels of BM fibronectin and perlecan were similar among all groups. Conclusions Cortical MV density and diameter are not appreciably altered by ADNC or CAA. TSG-6 and HA are increased in both ADNC and CAA, with laminin and col IV decreased in the BM of high ADNC, but laminin increased in moderate-severe CAA. These results show that changes in the ECM occur in AD and CAA, but independently of one another, and likely reflect on the regional functioning of the brain microvasculature.http://link.springer.com/article/10.1186/s12987-020-00219-yHuman neuropathologyAlzheimer’s diseaseCerebral amyloid angiopathyVascular densityVascular diameterLaminin |
| spellingShingle | Mamatha Damodarasamy Robert B. Vernon Jasmine L. Pathan C. Dirk Keene Anthony J. Day William A. Banks May J. Reed The microvascular extracellular matrix in brains with Alzheimer’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA) Fluids and Barriers of the CNS Human neuropathology Alzheimer’s disease Cerebral amyloid angiopathy Vascular density Vascular diameter Laminin |
| title | The microvascular extracellular matrix in brains with Alzheimer’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA) |
| title_full | The microvascular extracellular matrix in brains with Alzheimer’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA) |
| title_fullStr | The microvascular extracellular matrix in brains with Alzheimer’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA) |
| title_full_unstemmed | The microvascular extracellular matrix in brains with Alzheimer’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA) |
| title_short | The microvascular extracellular matrix in brains with Alzheimer’s disease neuropathologic change (ADNC) and cerebral amyloid angiopathy (CAA) |
| title_sort | microvascular extracellular matrix in brains with alzheimer s disease neuropathologic change adnc and cerebral amyloid angiopathy caa |
| topic | Human neuropathology Alzheimer’s disease Cerebral amyloid angiopathy Vascular density Vascular diameter Laminin |
| url | http://link.springer.com/article/10.1186/s12987-020-00219-y |
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