Holton, J.L.;
Ghiso, J.;
Lashle, T.;
Rostagno, A.;
Guerin, C.J.;
Gibb, G.;
Houlden, H.;
... Revesz, T.; + view all
(2001)
Regional distribution of amyloid-Bri deposition and its association with neurofibrillary degeneration in familial British dementia.
American Journal of Pathology
, 158
(2)
pp. 515-526.
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Abstract
Familial British dementia (FBD), pathologically characterized by cerebral amyloid angiopathy (CAA), amyloid plaques, and neurofibrillary degeneration, is associated with a stop codon mutation in the BRI gene resulting in the production of an amyloidogenic fragment, amyloid-Bri (ABri). The aim of this study was to assess the distribution of ABri fibrillar and nonfibrillar lesions and their relationship to neurofibrillary pathology, astroglial and microglial response using immunohistochemistry, confocal microscopy, and immunoelectron microscopy in five cases of FBD. Abnormal tau was studied with immunoblotting. We present evidence that ABri is deposited throughout the central nervous system in blood vessels and parenchyma where both amyloid (fibrillar) and pre-amyloid (nonfibrillar) lesions are formed. Ultrastructurally amyloid lesions appear as bundles of fibrils recognized by an antibody raised against ABri, whereas Thioflavin S-negative diffuse deposits consist of amorphous electron-dense material with sparse, dispersed fibrils. In contrast to nonfibrillar lesions, fibrillar ABri is associated with a marked astrocytic and microglial response. Neurofibrillary tangles and neuropil threads occurring mainly in limbic structures, are found in areas affected by all types of ABri lesions whereas abnormal neurites are present around amyloid lesions. Immunoblotting for tau revealed a triplet electrophoretic migration pattern. Our observations confirm a close link between ABri deposition and neurodegeneration in FBD.
| Type: | Article |
|---|---|
| Title: | Regional distribution of amyloid-Bri deposition and its association with neurofibrillary degeneration in familial British dementia |
| Open access status: | An open access version is available from UCL Discovery |
| Publisher version: | http://ajp.amjpathol.org/cgi/content/abstract/158/... |
| Language: | English |
| Additional information: | Copyright-American Society for Investigative Pathology Reprinted from The American Journal of Pathology with permission from the American Society for Investigative Pathology. Any reproduction or reuse of this material, including but not limited to reformatting, reposting, republication, translation, or other derivative works based on any portion of this article, will require separate permission from the Publisher (ASIP). Definitive version of this article appears on http://www.amjpathol.org |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/7462 |
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