Regional distribution of amyloid-Bri deposition and its association with neurofibrillary degeneration in familial British dementia

Janice L. Holton, Jorge Ghiso, Tammaryn Lashley, Agueda Rostagno, Christopher J. Guerin, Graham Gibb, Henry Houlden, Hilary Ayling, Lillian Martinian, Brian H. Anderton, Nicholas W. Wood, Ruben Vidal, Gordon Plant, Blas Frangione, Tamas Revesz

Research output: Contribution to journalArticle

105 Scopus citations

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 preamyloid (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.

Original languageEnglish (US)
Article number63993
Pages (from-to)515-526
Number of pages12
JournalAmerican Journal of Pathology
Volume158
Issue number2
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Regional distribution of amyloid-Bri deposition and its association with neurofibrillary degeneration in familial British dementia'. Together they form a unique fingerprint.

  • Cite this

    Holton, J. L., Ghiso, J., Lashley, T., Rostagno, A., Guerin, C. J., Gibb, G., Houlden, H., Ayling, H., Martinian, L., Anderton, B. H., Wood, N. W., Vidal, R., Plant, G., Frangione, B., & Revesz, T. (2001). Regional distribution of amyloid-Bri deposition and its association with neurofibrillary degeneration in familial British dementia. American Journal of Pathology, 158(2), 515-526. [63993]. https://doi.org/10.1016/S0002-9440(10)63993-4