Antibodies to fibronectin bind to plaques and other structures in Alzheimer's disease and control brain

Howard, Jonathan; Pilkington, Geoffrey J.

doi:10.1016/0304-3940(90)90251-4

Cited by 26 publications

(14 citation statements)

References 11 publications

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“…Laminin-1, type IV collagen and heparansulfate proteoglycans have all been local- ized within the senile plaques as punctate deposits (Perlmutter et al, 1991;Murtomäki et al, 1992;Berzin et al, 2000). Over-expression of the ␥1 laminin in reactive astrocytes of the diseased human brain was reported in 1992 (Murtomäki et al, 1992) whereas the presence of additional matrix proteins, such as fibronectin, remains controversial (Koike et al, 1988;Howard and Pilkington, 1990). In recent years, new insight has emerged in understanding the expression of laminin-1 in the Alzheimer brain tissue (Morgan and Inestrosa, 2001).…”

Section: Discussionmentioning

confidence: 97%

Differential distribution of laminins in Alzheimer disease and normal human brain tissue

Palu

Liesi

2002

J of Neuroscience Research

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Immunocytochemistry, Western blotting, and RT-PCR were used to identify the isoforms of laminin expressed in the Alzheimer disease, but not in normal human brain tissue. We found that alpha 1 laminin was heavily over-expressed in Alzheimer disease frontal cortex, and localized in reactive astrocytes of the grey and white matter, and as punctate deposits in the senile placques of the Alzheimer brain tissue. Antibodies against the C-terminal neurite outgrowth domain of the gamma 1 laminin demonstrated expression of the gamma 1 laminin in GFAP-immunoreactive reactive astrocytes of the Alzheimer disease frontal cortex. The gamma 1 laminin was also heavily over-expressed in reactive astrocytes of both grey and white matter. Although antibodies against the C-terminal neurite outgrowth domain failed to localize gamma 1 laminin in senile plaques, antibodies against the N-terminal domains of the gamma 1 laminin demonstrated gamma 1 laminin as punctate deposits in the senile plaques. The present results indicate that enhanced and specialized expression patterns of alpha 1 and gamma 1 laminins distinctly associate these two laminins with the Alzheimer disease. The fact that domain specific antibodies localize both alpha1 and gamma 1 laminins in the senile plaques as punctate deposits and in astrocytes of both the gray and white matter indicate that these laminins and their specific domains may have distinct functions in the pathophysiology of the Alzheimer disease.

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Section: Discussionmentioning

confidence: 97%

Differential distribution of laminins in Alzheimer disease and normal human brain tissue

Palu

Liesi

2002

J of Neuroscience Research

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“…The appearance of laminin and its receptor VLA-6 in the neuropil of adult brain is remarkable because laminin is not expressed in the fully developed brain. There are contrasting data on the presence of fibronectin in amyloid plaques; Koike et al (1988) reported no immunostaining but Howard and Pilkington (1990) found immunoreactivity. The presence of laminin in the corona of classical plaques agrees with the suggestion that neurites in amyloid plaques may show an aberrant regeneration response (Geddes et al 1985).…”

Section: Discussionmentioning

confidence: 98%

“…Using immunohistochemical techniques, the serine protease inhibitors c~l-antichymotrypsin (Abraham et al 1988) and serum amyloid P component (Coria et al 1988) as well as several complement factors (Eikelenboom and Stam 1982;Ishii and Haga 1984) are found in both amorphous and classical plaques (Rozemuller et al 1989b). 1992) but there are contradictory data on the presence of fibronectin in plaques (Koike et al 1988;Howard and Pilkington 1990). The presence of activated proteases and protease inhibitors is interesting as there is a delicate balance between proteases and protease inhibitors that modulates neurite elongation and regeneration (Monard 1988).…”

Section: Introductionmentioning

confidence: 99%

Cellular and substrate adhesion molecules (integrins) and their ligands in cerebral amyloid plaques in Alzheimer's disease

Eikelenboom

Zhan

Kamphorst

et al. 1994

Vichows Archiv A Pathol Anat

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Integrins belonging to different subfamilies can be identified immunohistochemically in cerebral amyloid plaques. Monoclonal antibodies against the VLA family beta 1-integrins show staining of the corona of classical amyloid plaques for beta 1, alpha 3 and alpha 6. Immunostaining reveal also the presence of collagen and laminin in the corona. Activated microglial cells in classical plaques strongly express receptors belonging to the LeuCAM family (beta 2 integrins). The ligands ICAM and activated complement C3 are found in both amorphous and classical plaques. Vitronectin receptor (alpha v) is found in glial cells in classical plaques but its ligand vitronectin is seen in both amorphous and classical plaques. The data presented here demonstrate the presence of different cellular and substrate adhesive molecules (integrins) and their ligands in classical plaques. The findings suggest that amyloid plaques show signs of regeneration and tissue remodelling.

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“…Sci. USA 90 (1993) colocalized to Af3 deposits in cortical senile plaques and cerebral vessels in AD brains (19)(20)(21)(22) (23,24), a finding that has been interpreted to suggest that neuritic alteration is the initial stage in neuritic plaque formation (25). In light of our results, the neuritic response found in some plaque-rich cortex, if interpreted to represent sprouting rather than degenerating neurites, may be secondary to the presence of insoluble nonaggregated AP3 complexed with ECM components-possibly laminin, fibronectin, or other ECM molecules-in the vicinity.…”

Section: Discussionmentioning

confidence: 99%

Amyloid beta-protein as a substrate interacts with extracellular matrix to promote neurite outgrowth.

Koo

Park

Selkoe

1993

Proc. Natl. Acad. Sci. U.S.A.

161

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Progressive deposition of amyloid 3-protein In brain, whether A,B has any physiological role is unknown. Studies aimed at elucidating the biological effects of A/3 on the nervous system have yielded equivocal results. Addition of synthetic peptides corresponding to the first 28 or 42 amino acids of the Al3 sequence to culture medium resulted in a dose-dependent effect on survival and neurite outgrowth of rat hippocampal neurons (3, 4). With a similar paradigm, AP-(1-40) peptide was found to be both trophic and toxic to hippocampal neurons, depending on the peptide dose and maturity ofthe neurons in vitro (5). In such systems, increased evidence favors a role of excitatory amino acids in A,B-induced neurotoxicity (6), possibly because A,B destabilizes calcium homeostasis (7). A recent study further suggested that peptide aggregation may enhance A,B toxicity in cultured hippocampal neurons (8). Finally, two reports suggested that transfection of either full-length APP or its C-terminal 100 residues, both ofwhich contain the AP region, into neural cells may result in cell degeneration upon neuronal differentiation (9, 10).Central to many of these studies is the addition of soluble AP3 in relatively high concentrations to culture medium. In one study, acetonitrile and trifluoroacetic acid were used to solubilize A,B before addition to culture medium (5 show that immobilized A,B has no detrimental effect on neurite outgrowth. On the contrary, in the presence of low amounts of extracellular matrix (ECM) components, A,B promotes neurite outgrowth in a dose-dependent manner. MATERIALS AND METHODSPeptides. Six synthetic peptides were used: AP-(1-40),A,B-(1-28), and A,B-(21-37) (all from the human APP sequence) and, as controls, a 40-residue peptide having all A,B amino acids but randomly scrambled (NH2-VIEVLVGE-LDAFDGHVAGFSHDQKGNHVKGGARYMVSIFE), the 37-residue islet amyloid polypeptide (amylin; Peninsula Laboratories), and a 10-residue substance P peptide (Peninsula Laboratories). All peptides were HPLC purified, and the first four peptides were additionally analyzed by mass spectroscopy. All peptides were dissolved in deionized water at a concentration of 1 mg/ml. A sample of AP3 peptide was aggregated before use by dissolving in phosphate-buffered saline at 10 mg/ml, incubating at 37°C for 48 hr, and storing at 4°C for 1 week. The peptide was resuspended in water at 1 mg/ml just before use. On SDS/PAGE, the sample consisted primarily of mono-and dimeric forms, with smaller amounts of tetrameric aggregates. Substrate Preparation. Tissue culture substrates were prepared under sterile conditions by coating 35-mm Petri dishes with a premixed solution consisting of peptide, ECM, or both. All dishes were coated with peptide concentrations ranging from 0.5 to 5.0 pug/cm2. The ECM component con- §To whom reprint requests should be addressed. 4748The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C...

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Antibodies to fibronectin bind to plaques and other structures in Alzheimer's disease and control brain

Cited by 26 publications

References 11 publications

Differential distribution of laminins in Alzheimer disease and normal human brain tissue

Differential distribution of laminins in Alzheimer disease and normal human brain tissue

Cellular and substrate adhesion molecules (integrins) and their ligands in cerebral amyloid plaques in Alzheimer's disease

Amyloid beta-protein as a substrate interacts with extracellular matrix to promote neurite outgrowth.

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