Basic fibroblast growth factor binding is a marker for extracellular neurofibrillary tangles in Alzheimer disease

Neurofibrillary tangles (NFT) are abnormal filamentous inclusions that develop in neurons in Alzheimer disease and other disorders. When neurons die, the neurofibrillary tangles that persist in the extracellular space show ultrastructural and antigenic changes. Both intra- and extracellular NFT have...

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Bibliographic Details
Published in:The journal of histochemistry and cytochemistry 1991-07, Vol.39 (7), p.899-904
Main Authors: Siedlak, SL, Cras, P, Kawai, M, Richey, P, Perry, G
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Biological and medical sciences
Biomarkers
Cell structures and functions
Fibroblast Growth Factor 2 - metabolism
Fundamental and applied biological sciences. Psychology
Hippocampus - metabolism
Hippocampus - ultrastructure
Humans
Microscopy, Electron
Molecular and cellular biology
Neurofibrils - metabolism
Neurofibrils - ultrastructure
Temporal Lobe - metabolism
Temporal Lobe - ultrastructure
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Summary:Neurofibrillary tangles (NFT) are abnormal filamentous inclusions that develop in neurons in Alzheimer disease and other disorders. When neurons die, the neurofibrillary tangles that persist in the extracellular space show ultrastructural and antigenic changes. Both intra- and extracellular NFT have recently been shown to contain heparan sulfate proteoglycans (HSPGs). HSPGs are also present in other amyloid deposits in the brain and in systemic amyloidoses. Basic fibroblast growth factor (bFGF) is a heparin binding growth factor which is involved in angiogenesis and also has neurite promoting activity. We now report that bFGF binds avidly to extracellular NFT. Alz-50, a monoclonal antibody (MAb) to an abnormal form of tau and bFGF binding label mutually exclusive subpopulations of neurofibrillary tangles. bFGF binding is abolished by heparinase or heparitinase treatment and therefore is most likely based on the presence of HSPG. Binding of bFGF is a specific and sensitive morphological method to distinguish intra- from extracellular NFT. As intracellular NFT, which also contain HSPGs, are not labeled by bFGF binding, this finding also suggests that HSPGs are modified when the NFT become extracellular.
ISSN:0022-1554
1551-5044
DOI:10.1177/39.7.1865106