Aβ(1–40) Prevents Heparanase-catalyzed Degradation of Heparan Sulfate Glycosaminoglycans and Proteoglycans in Vitro

Alzheimer's disease is characterized by senile plaques composed of polymeric fibrils of beta amyloid (Aβ), a 39–42-amino acid peptide formed after proteolytic processing of the amyloid precursor protein (βAPP). Heparan sulfate proteoglycans have been shown to colocalize with Aβ in Alzheimer's disease brain, and experimental evidence indicates that the interactions between the proteoglycan and the peptide are important for the promotion, deposition, and/or persistence of the senile plaques. Studies in rat brain indicated that both the core protein and the heparan sulfate glycosaminoglycan chains are required for amyloid fiber formation and deposition in vivo (Snow, A. D., Sekiguchi, R., Nochlin, D., Fraser, P., Kimata, K., Mizutani, A., Arai, M., Schreier, W. A., and Morgan, D. G. (1994) Neuron 12, 219–234), suggesting that one mechanism to prevent the formation of Aβ-heparan sulfate proteoglycan complexes that lead to deposition of amyloid would be to degrade the proteoglycan. Normally, heparan sulfate proteoglycans are internalized and degraded to short glycosaminoglycans by intracellular heparanases. These reactions occur in the endosomal-lysosomal pathway, which is the same intracellular location where βAPP is processed to Aβ. Using partially purified heparanase activities from Chinese hamster ovary cells we examined whether Aβ(1–40) affects the catabolism of Chinese hamster ovary heparan sulfate glycosaminoglycans and proteoglycans in vitro. Aβ(1–40) binds to both the long heparan sulfate glycosaminoglycans attached to core proteins and the short, heparanase-derived chains in a concentration-dependent and pH-dependent manner. When Aβ(1–40) is added to heparanase assays, it prevents the partially purified activities from releasing heparan sulfate chains from core proteins and degrading them to short glycosaminoglycans; however, a large molar excess of the peptide to heparan sulfate is required to see the effect. Our results suggest that normally the levels of Aβ in the endosomal pathway are not sufficient to interfere with heparanase activity in vivo. However, once the level of Aβ-peptides are elevated, as they are in Alzheimer's disease, they could interact with heparan sulfate proteoglycans and prevent their catabolism. This could promote the formation and deposition of amyloid, since the binding of Aβ to the proteoglycan species will predominate. Alzheimer's disease is characterized by senile plaques composed of polymeric fibrils of beta amyloid (Aβ), a 39–42-amino acid peptide formed after proteolytic processing of the amyloid precursor protein (βAPP). Heparan sulfate proteoglycans have been shown to colocalize with Aβ in Alzheimer's disease brain, and experimental evidence indicates that the interactions between the proteoglycan and the peptide are important for the promotion, deposition, and/or persistence of the senile plaques. Studies in rat brain indicated that both the core protein and the heparan sulfate glycosaminoglycan chains are required for amyloid fiber formation and deposition in vivo (Snow, A. D., Sekiguchi, R., Nochlin, D., Fraser, P., Kimata, K., Mizutani, A., Arai, M., Schreier, W. A., and Morgan, D. G. (1994) Neuron 12, 219–234), suggesting that one mechanism to prevent the formation of Aβ-heparan sulfate proteoglycan complexes that lead to deposition of amyloid would be to degrade the proteoglycan. Normally, heparan sulfate proteoglycans are internalized and degraded to short glycosaminoglycans by intracellular heparanases. These reactions occur in the endosomal-lysosomal pathway, which is the same intracellular location where βAPP is processed to Aβ. Using partially purified heparanase activities from Chinese hamster ovary cells we examined whether Aβ(1–40) affects the catabolism of Chinese hamster ovary heparan sulfate glycosaminoglycans and proteoglycans in vitro. Aβ(1–40) binds to both the long heparan sulfate glycosaminoglycans attached to core proteins and the short, heparanase-derived chains in a concentration-dependent and pH-dependent manner. When Aβ(1–40) is added to heparanase assays, it prevents the partially purified activities from releasing heparan sulfate chains from core proteins and degrading them to short glycosaminoglycans; however, a large molar excess of the peptide to heparan sulfate is required to see the effect. Our results suggest that normally the levels of Aβ in the endosomal pathway are not sufficient to interfere with heparanase activity in vivo. However, once the level of Aβ-peptides are elevated, as they are in Alzheimer's disease, they could interact with heparan sulfate proteoglycans and prevent their catabolism. This could promote the formation and deposition of amyloid, since the binding of Aβ to the proteoglycan species will predominate. Histochemical and immunocytochemical studies have shown that heparan sulfate (HS) 1The abbreviations used are: HS, heparan sulfate; HSPG, heparan sulfate proteoglycan; Aβ, β-amyloid; CHO, Chinese hamster ovary; CHAPS, 3-(3-cholamidopropyl)dimethylammonio-1-propanesulfonic acid; βAPP, β-amyloid precursor protein; CPC, cetyl pyridinium chloride. 1The abbreviations used are: HS, heparan sulfate; HSPG, heparan sulfate proteoglycan; Aβ, β-amyloid; CHO, Chinese hamster ovary; CHAPS, 3-(3-cholamidopropyl)dimethylammonio-1-propanesulfonic acid; βAPP, β-amyloid precursor protein; CPC, cetyl pyridinium chloride. proteoglycans (HSPGs) and glycosaminoglycans colocalize with β-amyloid protein (Aβ) in the senile plaques characteristic of Alzheimer's disease (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google Scholar). Although the precise role of the proteoglycans in the process of amyloidosis is not known, experimental evidence suggests that they may promote amyloid formation, deposition, and/or persistence (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google Scholar) by binding to Aβ PubMed Scopus Google PubMed Scopus Google W. A. PubMed Scopus Google W. R. A. PubMed Scopus Google Scholar). are of one glycosaminoglycan chains attached to a core protein G. PubMed Scopus Google Scholar). Aβ binds to with and it with both the core protein and the glycosaminoglycan chains PubMed Scopus Google W. A. PubMed Scopus Google Scholar). by (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google Scholar) suggest that both interactions are for the formation of since of Aβ(1–40) and rat brain of Aβ(1–40) and glycosaminoglycans This is since in chains both and Aβ(1–40) to PubMed Scopus Google and PubMed Scopus Google Scholar). may be that in of the and amyloid to Aβ to interact with both the core protein and of Aβ from the amyloid precursor protein is to occur in the endosomal-lysosomal pathway Full Text PDF PubMed Scopus Google 1994; Full Text PDF PubMed Google M. Full Text Full Text PDF PubMed Scopus Google Scholar). are degraded to short glycosaminoglycan chains in the same intracellular location M. Full Text PDF PubMed Google Full Text PDF PubMed Google Full Text PDF PubMed Google it is that is where the for formation glycosaminoglycans are from core proteins and to short by M. Full Text PDF PubMed Google Full Text PDF PubMed Google Full Text PDF PubMed Google K. Full Text Full Text PDF PubMed Scopus Google Scholar). of by may be important for the formation of complexes that in the of amyloid the the glycosaminoglycan and core protein binding will have been Aβ may be to to the core the short glycosaminoglycans the protein may not be sufficient to the interactions for fiber formation and studies Aβ peptide is from by of with glycosaminoglycans R. Full Text Full Text PDF PubMed Scopus Google Scholar). may be that a where the of Aβ with the prevents from degrading the heparanase may promote the formation of amyloid plaques since the binding of Aβ to proteoglycans will predominate. Using partially purified heparanase activities from Chinese hamster ovary we have examined whether Aβ(1–40) peptide affects the catabolism of glycosaminoglycans and proteoglycans in vitro. Our results suggest that the of Aβ with the glycosaminoglycan from by disease is characterized by amyloid senile composed of polymeric fibrils of Aβ, a 39–42-amino acid peptide formed after proteolytic processing of the amyloid precursor protein M. PubMed Scopus Google Scholar). of colocalize with Aβ in the (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google R. Full Text Full Text PDF PubMed Scopus Google Scholar). the a of experimental evidence which indicates a role in the promotion, deposition, and persistence of the of Aβ in plaques (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google PubMed Scopus Google PubMed Scopus Google R. Full Text Full Text PDF PubMed Scopus Google Scholar). glycosaminoglycans Aβ PubMed Scopus Google Aβ to PubMed Scopus Google and the Aβ from R. Full Text Full Text PDF PubMed Scopus Google Scholar). the glycosaminoglycan is required for interactions in both the and the core protein are required for amyloid fiber formation and deposition in vivo (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google Scholar). Aβ been shown to to both the glycosaminoglycan and core protein W. A. PubMed Scopus Google W. R. A. PubMed Scopus Google it may be that both interactions are formation and deposition of Aβ may to that the the glycosaminoglycan chains be a core proteoglycans are important species for formation of senile plaques in one would that their catabolism may important role in Alzheimer's glycosaminoglycans are from the core protein and degraded to short by M. Full Text PDF PubMed Google Full Text PDF PubMed Google Scholar). Our in studies Aβ(1–40) prevents partially purified heparanase activities from degrading long chains to short large molar excess of Aβ(1–40) to required to by suggests that of the peptide the 1994; Full Text PDF PubMed Google Scholar) that Aβ(1–40) and Aβ species could to the the of the peptide to is 1994; Full Text PDF PubMed Google which is the of Aβ(1–40) where we of heparanase activity This suggests that Aβ(1–40) with and with chains that in the glycosaminoglycan from heparanases. their 1994; Full Text PDF PubMed Google Scholar) that Aβ fibrils are as with the of the Aβ peptide the and the in the chains may the of the of interactions between sulfate the and the chains in the of Aβ PubMed Scopus Google R. Full Text Full Text PDF PubMed Scopus Google Scholar). once the is with the R. R. PubMed Scopus Google Scholar) is that the glycosaminoglycan is by heparanases. Aβ(1–40) it may be that fibrils are a of the chains is to the However, once the of the peptide is to the glycosaminoglycan with the fibrils and is from Aβ the glycosaminoglycans may promote interactions between Aβ to the in Alzheimer's the of Aβ with glycosaminoglycan chains prevents from degrading in to Alzheimer's is evidence that once βAPP the it is internalized and by to that the Aβ 1994; Full Text PDF PubMed Google M. PubMed Scopus Google Scholar). suggest the of in the Full Text PDF PubMed Scopus Google 1994; Full Text PDF PubMed Google M. PubMed Scopus Google Scholar). This is the same intracellular where degrading M. Full Text PDF PubMed Google Full Text PDF PubMed Google Full Text PDF PubMed Google Scholar). the of in to M. PubMed Scopus Google Scholar) will be to catabolism of the However, once the levels of Aβ are in Alzheimer's disease, the could fibrils and interact with the in of Aβ with the proteoglycan would prevent from degrading the glycosaminoglycans the core protein to short This will in level of which could the and prevent them from degraded by (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google R. Full Text Full Text PDF PubMed Scopus Google is by that suggest that Aβ the of of βAPP cells M. Full Text Full Text PDF PubMed Scopus Google Scholar). When is added to the of it is internalized in a concentration-dependent M. Full Text Full Text PDF PubMed Scopus Google D. A. PubMed Scopus Google Scholar) and in D. A. PubMed Scopus Google Scholar). of in the of peptide internalized D. A. PubMed Scopus Google suggesting that the of cells is sufficient to catabolism by heparanases. the cells with βAPP to the levels of the added the of from the precursor which the M. Full Text Full Text PDF PubMed Scopus Google Scholar). that the from βAPP by with the and them to the M. Full Text Full Text PDF PubMed Scopus Google in studies not whether the with D. A. PubMed Scopus Google it is that they to in of interactions with R. Full Text Full Text PDF PubMed Scopus Google Scholar). the the of the proteoglycans would be to interact with the Aβ and them to species that are to would be to the of to glycosaminoglycans in cells with βAPP and see the cells are in the of the of is catabolism of be a of the cells are with in the of intracellular of with Aβ may a role in the formation of the in Alzheimer's When protein is with in to are formed M. R. M. PubMed Scopus Google Scholar). of Alzheimer's disease brain suggests that of may be the in the process M. R. M. PubMed Scopus Google Scholar). it is that in catabolism may be a to the formation of both plaques and of heparanase activity may have the formation of Aβ that Aβ(1–40) could to both the long chains core proteins and the short glycosaminoglycans by and that the short could with the long chains for the peptide studies by (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google Scholar) would suggest that complexes formed between and short chains not lead to amyloid and have that glycosaminoglycans proteoglycans to A. W. 1994; Google Scholar) Aβ(1–40) fibrils R. Fraser W.A. PubMed Scopus Google Scholar). in to degrading the proteoglycan species that would be in senile may be glycosaminoglycan species that to prevent Aβ and Histochemical and immunocytochemical studies have shown that heparan sulfate (HS) 1The abbreviations used are: HS, heparan sulfate; HSPG, heparan sulfate proteoglycan; Aβ, β-amyloid; CHO, Chinese hamster ovary; CHAPS, 3-(3-cholamidopropyl)dimethylammonio-1-propanesulfonic acid; βAPP, β-amyloid precursor protein; CPC, cetyl pyridinium chloride. 1The abbreviations used are: HS, heparan sulfate; HSPG, heparan sulfate proteoglycan; Aβ, β-amyloid; CHO, Chinese hamster ovary; CHAPS, 3-(3-cholamidopropyl)dimethylammonio-1-propanesulfonic acid; βAPP, β-amyloid precursor protein; CPC, cetyl pyridinium chloride. proteoglycans (HSPGs) and glycosaminoglycans colocalize with β-amyloid protein (Aβ) in the senile plaques characteristic of Alzheimer's disease (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google Scholar). Although the precise role of the proteoglycans in the process of amyloidosis is not known, experimental evidence suggests that they may promote amyloid formation, deposition, and/or persistence (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google Scholar) by binding to Aβ PubMed Scopus Google PubMed Scopus Google W. A. PubMed Scopus Google W. R. A. PubMed Scopus Google Scholar). are of one glycosaminoglycan chains attached to a core protein G. PubMed Scopus Google Scholar). Aβ binds to with and it with both the core protein and the glycosaminoglycan chains PubMed Scopus Google W. A. PubMed Scopus Google Scholar). by (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google Scholar) suggest that both interactions are for the formation of since of Aβ(1–40) and rat brain of Aβ(1–40) and glycosaminoglycans This is since in chains both and Aβ(1–40) to PubMed Scopus Google and PubMed Scopus Google Scholar). may be that in of the and amyloid to Aβ to interact with both the core protein and of Aβ from the amyloid precursor protein is to occur in the endosomal-lysosomal pathway Full Text PDF PubMed Scopus Google 1994; Full Text PDF PubMed Google M. Full Text Full Text PDF PubMed Scopus Google Scholar). are degraded to short glycosaminoglycan chains in the same intracellular location M. Full Text PDF PubMed Google Full Text PDF PubMed Google Full Text PDF PubMed Google it is that is where the for formation glycosaminoglycans are from core proteins and to short by M. Full Text PDF PubMed Google Full Text PDF PubMed Google Full Text PDF PubMed Google K. Full Text Full Text PDF PubMed Scopus Google Scholar). of by may be important for the formation of complexes that in the of amyloid the the glycosaminoglycan and core protein binding will have been Aβ may be to to the core the short glycosaminoglycans the protein may not be sufficient to the interactions for fiber formation and studies Aβ peptide is from by of with glycosaminoglycans R. Full Text Full Text PDF PubMed Scopus Google Scholar). may be that a where the of Aβ with the prevents from degrading the heparanase may promote the formation of amyloid plaques since the binding of Aβ to proteoglycans will predominate. Using partially purified heparanase activities from Chinese hamster ovary we have examined whether Aβ(1–40) peptide affects the catabolism of glycosaminoglycans and proteoglycans in vitro. Our results suggest that the of Aβ with the glycosaminoglycan from by heparanases. disease is characterized by amyloid senile composed of polymeric fibrils of Aβ, a 39–42-amino acid peptide formed after proteolytic processing of the amyloid precursor protein M. PubMed Scopus Google Scholar). of colocalize with Aβ in the (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google R. Full Text Full Text PDF PubMed Scopus Google Scholar). the a of experimental evidence which indicates a role in the promotion, deposition, and persistence of the of Aβ in plaques (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google PubMed Scopus Google PubMed Scopus Google R. Full Text Full Text PDF PubMed Scopus Google Scholar). glycosaminoglycans Aβ PubMed Scopus Google Aβ to PubMed Scopus Google and the Aβ from R. Full Text Full Text PDF PubMed Scopus Google Scholar). the glycosaminoglycan is required for interactions in both the and the core protein are required for amyloid fiber formation and deposition in vivo (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google Scholar). Aβ been shown to to both the glycosaminoglycan and core protein W. A. PubMed Scopus Google W. R. A. PubMed Scopus Google it may be that both interactions are formation and deposition of Aβ may to that the the glycosaminoglycan chains be a core proteoglycans are important species for formation of senile plaques in one would that their catabolism may important role in Alzheimer's glycosaminoglycans are from the core protein and degraded to short by M. Full Text PDF PubMed Google Full Text PDF PubMed Google Scholar). Our in studies Aβ(1–40) prevents partially purified heparanase activities from degrading long chains to short large molar excess of Aβ(1–40) to required to by suggests that of the peptide the 1994; Full Text PDF PubMed Google Scholar) that Aβ(1–40) and Aβ species could to the the of the peptide to is 1994; Full Text PDF PubMed Google which is the of Aβ(1–40) where we of heparanase activity This suggests that Aβ(1–40) with and with chains that in the glycosaminoglycan from heparanases. their 1994; Full Text PDF PubMed Google Scholar) that Aβ fibrils are as with the of the Aβ peptide the and the in the chains may the of the of interactions between sulfate the and the chains in the of Aβ PubMed Scopus Google R. Full Text Full Text PDF PubMed Scopus Google Scholar). once the is with the R. R. PubMed Scopus Google Scholar) is that the glycosaminoglycan is by heparanases. Aβ(1–40) it may be that fibrils are a of the chains is to the However, once the of the peptide is to the glycosaminoglycan with the fibrils and is from Aβ the glycosaminoglycans may promote interactions between Aβ to the in Alzheimer's the of Aβ with glycosaminoglycan chains prevents from degrading in to Alzheimer's is evidence that once βAPP the it is internalized and by to that the Aβ 1994; Full Text PDF PubMed Google M. PubMed Scopus Google Scholar). suggest the of in the Full Text PDF PubMed Scopus Google 1994; Full Text PDF PubMed Google M. PubMed Scopus Google Scholar). This is the same intracellular where degrading M. Full Text PDF PubMed Google Full Text PDF PubMed Google Full Text PDF PubMed Google Scholar). the of in to M. PubMed Scopus Google Scholar) will be to catabolism of the However, once the levels of Aβ are in Alzheimer's disease, the could fibrils and interact with the in of Aβ with the proteoglycan would prevent from degrading the glycosaminoglycans the core protein to short This will in level of which could the and prevent them from degraded by (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google R. Full Text Full Text PDF PubMed Scopus Google is by that suggest that Aβ the of of βAPP cells M. Full Text Full Text PDF PubMed Scopus Google Scholar). When is added to the of it is internalized in a concentration-dependent M. Full Text Full Text PDF PubMed Scopus Google D. A. PubMed Scopus Google Scholar) and in D. A. PubMed Scopus Google Scholar). of in the of peptide internalized D. A. PubMed Scopus Google suggesting that the of cells is sufficient to catabolism by heparanases. the cells with βAPP to the levels of the added the of from the precursor which the M. Full Text Full Text PDF PubMed Scopus Google Scholar). that the from βAPP by with the and them to the M. Full Text Full Text PDF PubMed Scopus Google in studies not whether the with D. A. PubMed Scopus Google it is that they to in of interactions with R. Full Text Full Text PDF PubMed Scopus Google Scholar). the the of the proteoglycans would be to interact with the Aβ and them to species that are to would be to the of to glycosaminoglycans in cells with βAPP and see the cells are in the of the of is catabolism of be a of the cells are with in the of intracellular of with Aβ may a role in the formation of the in Alzheimer's When protein is with in to are formed M. R. M. PubMed Scopus Google Scholar). of Alzheimer's disease brain suggests that of may be the in the process M. R. M. PubMed Scopus Google Scholar). it is that in catabolism may be a to the formation of both plaques and of heparanase activity may have the formation of Aβ that Aβ(1–40) could to both the long chains core proteins and the short glycosaminoglycans by and that the short could with the long chains for the peptide studies by (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google Scholar) would suggest that complexes formed between and short chains not lead to amyloid and have that glycosaminoglycans proteoglycans to A. W. 1994; Google Scholar) Aβ(1–40) fibrils R. Fraser W.A. PubMed Scopus Google Scholar). in to degrading the proteoglycan species that would be in senile may be glycosaminoglycan species that to prevent Aβ and Alzheimer's disease is characterized by amyloid senile composed of polymeric fibrils of Aβ, a 39–42-amino acid peptide formed after proteolytic processing of the amyloid precursor protein M. PubMed Scopus Google Scholar). of colocalize with Aβ in the (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google R. Full Text Full Text PDF PubMed Scopus Google Scholar). the a of experimental evidence which indicates a role in the promotion, deposition, and persistence of the of Aβ in plaques (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google PubMed Scopus Google PubMed Scopus Google R. Full Text Full Text PDF PubMed Scopus Google Scholar). glycosaminoglycans Aβ PubMed Scopus Google Aβ to PubMed Scopus Google and the Aβ from R. Full Text Full Text PDF PubMed Scopus Google Scholar). the glycosaminoglycan is required for interactions in both the and the core protein are required for amyloid fiber formation and deposition in vivo (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google Scholar). Aβ been shown to to both the glycosaminoglycan and core protein W. A. PubMed Scopus Google W. R. A. PubMed Scopus Google it may be that both interactions are formation and deposition of Aβ may to that the the glycosaminoglycan chains be a core proteoglycans are important species for formation of senile plaques in one would that their catabolism may important role in Alzheimer's glycosaminoglycans are from the core protein and degraded to short by M. Full Text PDF PubMed Google Full Text PDF PubMed Google Scholar). Our in studies Aβ(1–40) prevents partially purified heparanase activities from degrading long chains to short large molar excess of Aβ(1–40) to required to by suggests that of the peptide the 1994; Full Text PDF PubMed Google Scholar) that Aβ(1–40) and Aβ species could to the the of the peptide to is 1994; Full Text PDF PubMed Google which is the of Aβ(1–40) where we of heparanase activity This suggests that Aβ(1–40) with and with chains that in the glycosaminoglycan from heparanases. their 1994; Full Text PDF PubMed Google Scholar) that Aβ fibrils are as with the of the Aβ peptide the and the in the chains may the of the of interactions between sulfate the and the chains in the of Aβ PubMed Scopus Google R. Full Text Full Text PDF PubMed Scopus Google Scholar). once the is with the R. R. PubMed Scopus Google Scholar) is that the glycosaminoglycan is by heparanases. Aβ(1–40) it may be that fibrils are a of the chains is to the However, once the of the peptide is to the glycosaminoglycan with the fibrils and is from Aβ the glycosaminoglycans may promote interactions between Aβ to the in Alzheimer's the of Aβ with glycosaminoglycan chains prevents from degrading in to Alzheimer's is evidence that once βAPP the it is internalized and by to that the Aβ 1994; Full Text PDF PubMed Google M. PubMed Scopus Google Scholar). suggest the of in the Full Text PDF PubMed Scopus Google 1994; Full Text PDF PubMed Google M. PubMed Scopus Google Scholar). This is the same intracellular where degrading M. Full Text PDF PubMed Google Full Text PDF PubMed Google Full Text PDF PubMed Google Scholar). the of in to M. PubMed Scopus Google Scholar) will be to catabolism of the However, once the levels of Aβ are in Alzheimer's disease, the could fibrils and interact with the in of Aβ with the proteoglycan would prevent from degrading the glycosaminoglycans the core protein to short This will in level of which could the and prevent them from degraded by (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google R. Full Text Full Text PDF PubMed Scopus Google Scholar). This is by that suggest that Aβ the of of βAPP cells M. Full Text Full Text PDF PubMed Scopus Google Scholar). When is added to the of it is internalized in a concentration-dependent M. Full Text Full Text PDF PubMed Scopus Google D. A. PubMed Scopus Google Scholar) and in D. A. PubMed Scopus Google Scholar). of in the of peptide internalized D. A. PubMed Scopus Google suggesting that the of cells is sufficient to catabolism by heparanases. the cells with βAPP to the levels of the added the of from the precursor which the M. Full Text Full Text PDF PubMed Scopus Google Scholar). that the from βAPP by with the and them to the M. Full Text Full Text PDF PubMed Scopus Google Scholar). in studies not whether the with D. A. PubMed Scopus Google it is that they to in of interactions with R. Full Text Full Text PDF PubMed Scopus Google Scholar). the the of the proteoglycans would be to interact with the Aβ and them to species that are to would be to the of to glycosaminoglycans in cells with βAPP and see the cells are in the of the of is catabolism of be a of the cells are with in the of intracellular of with Aβ may a role in the formation of the in Alzheimer's When protein is with in to are formed M. R. M. PubMed Scopus Google Scholar). of Alzheimer's disease brain suggests that of may be the in the process M. R. M. PubMed Scopus Google Scholar). it is that in catabolism may be a to the formation of both plaques and of heparanase activity may have the formation of Aβ that Aβ(1–40) could to both the long chains core proteins and the short glycosaminoglycans by and that the short could with the long chains for the peptide studies by (1Snow A.D. Sekiguchi R. Nochlin D. Fraser P. Kimata K. Mizutani A. Arai M. Schreier W.A. Morgan D.G. Neuron. 1994; 12: 219-234Abstract Full Text PDF PubMed Scopus (277) Google Scholar) would suggest that complexes formed between and short chains not lead to amyloid and have that glycosaminoglycans proteoglycans to A. W. 1994; Google Scholar) Aβ(1–40) fibrils R. Fraser W.A. PubMed Scopus Google Scholar). in to degrading the proteoglycan species that would be in senile may be glycosaminoglycan species that to prevent Aβ and for of the