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

103 Citations (Scopus)

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

Fingerprint

Amyloid
Immunoblotting
Neuropil Threads
Familial British Dementia
Cerebral Amyloid Angiopathy
Neurofibrillary Tangles
Immunoelectron Microscopy
Terminator Codon
Amyloid Plaques
Neurites
Confocal Microscopy
Blood Vessels
Central Nervous System
Immunohistochemistry
Electrons
Pathology
Mutation
Antibodies

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Regional distribution of amyloid-Bri deposition and its association with neurofibrillary degeneration in familial British dementia. / Holton, Janice L.; Ghiso, Jorge; Lashley, Tammaryn; Rostagno, Agueda; Guerin, Christopher J.; Gibb, Graham; Houlden, Henry; Ayling, Hilary; Martinian, Lillian; Anderton, Brian H.; Wood, Nicholas W.; Vidal, Ruben; Plant, Gordon; Frangione, Blas; Revesz, Tamas.

In: American Journal of Pathology, Vol. 158, No. 2, 63993, 01.01.2001, p. 515-526.

Research output: Contribution to journalArticle

Holton, JL, Ghiso, J, Lashley, T, Rostagno, A, Guerin, CJ, Gibb, G, Houlden, H, Ayling, H, Martinian, L, Anderton, BH, Wood, NW, 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, vol. 158, no. 2, 63993, pp. 515-526. https://doi.org/10.1016/S0002-9440(10)63993-4
Holton, Janice L. ; Ghiso, Jorge ; Lashley, Tammaryn ; Rostagno, Agueda ; Guerin, Christopher J. ; Gibb, Graham ; Houlden, Henry ; Ayling, Hilary ; Martinian, Lillian ; Anderton, Brian H. ; Wood, Nicholas W. ; Vidal, Ruben ; Plant, Gordon ; Frangione, Blas ; Revesz, Tamas. / Regional distribution of amyloid-Bri deposition and its association with neurofibrillary degeneration in familial British dementia. In: American Journal of Pathology. 2001 ; Vol. 158, No. 2. pp. 515-526.
@article{a6593f5239d2493fa462f393790b6442,
title = "Regional distribution of amyloid-Bri deposition and its association with neurofibrillary degeneration in familial British dementia",
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.",
author = "Holton, {Janice L.} and Jorge Ghiso and Tammaryn Lashley and Agueda Rostagno and Guerin, {Christopher J.} and Graham Gibb and Henry Houlden and Hilary Ayling and Lillian Martinian and Anderton, {Brian H.} and Wood, {Nicholas W.} and Ruben Vidal and Gordon Plant and Blas Frangione and Tamas Revesz",
year = "2001",
month = "1",
day = "1",
doi = "10.1016/S0002-9440(10)63993-4",
language = "English (US)",
volume = "158",
pages = "515--526",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Regional distribution of amyloid-Bri deposition and its association with neurofibrillary degeneration in familial British dementia

AU - Holton, Janice L.

AU - Ghiso, Jorge

AU - Lashley, Tammaryn

AU - Rostagno, Agueda

AU - Guerin, Christopher J.

AU - Gibb, Graham

AU - Houlden, Henry

AU - Ayling, Hilary

AU - Martinian, Lillian

AU - Anderton, Brian H.

AU - Wood, Nicholas W.

AU - Vidal, Ruben

AU - Plant, Gordon

AU - Frangione, Blas

AU - Revesz, Tamas

PY - 2001/1/1

Y1 - 2001/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0035137042&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035137042&partnerID=8YFLogxK

U2 - 10.1016/S0002-9440(10)63993-4

DO - 10.1016/S0002-9440(10)63993-4

M3 - Article

C2 - 11159188

AN - SCOPUS:0035137042

VL - 158

SP - 515

EP - 526

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 2

M1 - 63993

ER -