RGD Reference Report - Regional distribution of amyloid-Bri deposition and its association with neurofibrillary degeneration in familial British dementia. - Rat Genome Database

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

Authors: 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 
Citation: Holton JL, etal., Am J Pathol 2001 Feb;158(2):515-26.
RGD ID: 1358403
Pubmed: PMID:11159188   (View Abstract at PubMed)
PMCID: PMC1850296   (View Article at PubMed Central)
DOI: DOI:10.1016/S0002-9440(10)63993-4   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ITM2B-related cerebral amyloid angiopathy 1  IEP 1358403 RGD 
ITM2B-related cerebral amyloid angiopathy 1  ISOITM2B (Homo sapiens)1358403; 1358403 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Itm2b  (integral membrane protein 2B)

Genes (Mus musculus)
Itm2b  (integral membrane protein 2B)

Genes (Homo sapiens)
ITM2B  (integral membrane protein 2B)


Additional Information