Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain
Abstract Aged individuals with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by the age of 40 years. The purpose of the current study was to measure age-associated changes in APP processing in 36 individuals with DS (5 months–69 years) and in 26 controls (5 months–100 years...
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| Veröffentlicht in: | Neurobiology of aging 2007-10, Vol.28 (10), p.1493-1506 |
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| container_title | Neurobiology of aging |
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| creator | Nistor, M Don, M Parekh, M Sarsoza, F Goodus, M Lopez, G.E Kawas, C Leverenz, J Doran, E Lott, I.T Hill, M Head, E |
| description | Abstract Aged individuals with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by the age of 40 years. The purpose of the current study was to measure age-associated changes in APP processing in 36 individuals with DS (5 months–69 years) and in 26 controls (5 months–100 years). Alpha-secretase significantly decreased with age in DS, particularly in cases over the age of 40 years and was stable in controls. The levels of C-terminal fragments of APP reflecting alpha-secretase processing (CTF-alpha) decreased with age in both groups. In both groups, there was significant increase in beta-secretase activity with age. CTF-beta remained constant with age in controls suggesting compensatory increases in turnover/clearance mechanisms. In DS, young individuals had the lowest CTF-beta levels that may reflect rapid conversion of beta-amyloid (Aβ) to soluble pools or efficient CTF-beta clearance mechanisms. Treatments to slow or prevent AD in the general population targeting secretase activity may be more efficacious in adults with DS if combined with approaches that enhance Aβ degradation and clearance. |
| doi_str_mv | 10.1016/j.neurobiolaging.2006.06.023 |
| format | Article |
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The purpose of the current study was to measure age-associated changes in APP processing in 36 individuals with DS (5 months–69 years) and in 26 controls (5 months–100 years). Alpha-secretase significantly decreased with age in DS, particularly in cases over the age of 40 years and was stable in controls. The levels of C-terminal fragments of APP reflecting alpha-secretase processing (CTF-alpha) decreased with age in both groups. In both groups, there was significant increase in beta-secretase activity with age. CTF-beta remained constant with age in controls suggesting compensatory increases in turnover/clearance mechanisms. In DS, young individuals had the lowest CTF-beta levels that may reflect rapid conversion of beta-amyloid (Aβ) to soluble pools or efficient CTF-beta clearance mechanisms. Treatments to slow or prevent AD in the general population targeting secretase activity may be more efficacious in adults with DS if combined with approaches that enhance Aβ degradation and clearance.</description><identifier>ISSN: 0197-4580</identifier><identifier>EISSN: 1558-1497</identifier><identifier>DOI: 10.1016/j.neurobiolaging.2006.06.023</identifier><identifier>PMID: 16904243</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Aged ; Aging - metabolism ; Aging - pathology ; Alzheimer's disease ; Amyloid beta-Peptides - biosynthesis ; Amyloid beta-Protein Precursor - metabolism ; Amyloid Precursor Protein Secretases - metabolism ; Beta-amyloid ; Biomarkers - metabolism ; Brain - enzymology ; Brain - pathology ; Brain - physiopathology ; Child ; Child, Preschool ; Disease Progression ; Down Syndrome - enzymology ; Down Syndrome - pathology ; Down Syndrome - physiopathology ; Female ; Humans ; Infant ; Internal Medicine ; Male ; Middle Aged ; Neurology ; Oldest old ; Plaque, Amyloid - enzymology ; Plaque, Amyloid - pathology ; Reference Values ; Trisomy 21 ; Up-Regulation - physiology</subject><ispartof>Neurobiology of aging, 2007-10, Vol.28 (10), p.1493-1506</ispartof><rights>Elsevier Inc.</rights><rights>2006 Elsevier Inc.</rights><rights>2006 Elsevier Inc. All rights reserved. 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c645t-ad38a569e4789ad0d2e13643e5153c761d937024fc445b6faff27cadcfe84e703</citedby><cites>FETCH-LOGICAL-c645t-ad38a569e4789ad0d2e13643e5153c761d937024fc445b6faff27cadcfe84e703</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0197458006002326$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16904243$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nistor, M</creatorcontrib><creatorcontrib>Don, M</creatorcontrib><creatorcontrib>Parekh, M</creatorcontrib><creatorcontrib>Sarsoza, F</creatorcontrib><creatorcontrib>Goodus, M</creatorcontrib><creatorcontrib>Lopez, G.E</creatorcontrib><creatorcontrib>Kawas, C</creatorcontrib><creatorcontrib>Leverenz, J</creatorcontrib><creatorcontrib>Doran, E</creatorcontrib><creatorcontrib>Lott, I.T</creatorcontrib><creatorcontrib>Hill, M</creatorcontrib><creatorcontrib>Head, E</creatorcontrib><title>Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain</title><title>Neurobiology of aging</title><addtitle>Neurobiol Aging</addtitle><description>Abstract Aged individuals with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by the age of 40 years. The purpose of the current study was to measure age-associated changes in APP processing in 36 individuals with DS (5 months–69 years) and in 26 controls (5 months–100 years). Alpha-secretase significantly decreased with age in DS, particularly in cases over the age of 40 years and was stable in controls. The levels of C-terminal fragments of APP reflecting alpha-secretase processing (CTF-alpha) decreased with age in both groups. In both groups, there was significant increase in beta-secretase activity with age. CTF-beta remained constant with age in controls suggesting compensatory increases in turnover/clearance mechanisms. In DS, young individuals had the lowest CTF-beta levels that may reflect rapid conversion of beta-amyloid (Aβ) to soluble pools or efficient CTF-beta clearance mechanisms. Treatments to slow or prevent AD in the general population targeting secretase activity may be more efficacious in adults with DS if combined with approaches that enhance Aβ degradation and clearance.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aging - metabolism</subject><subject>Aging - pathology</subject><subject>Alzheimer's disease</subject><subject>Amyloid beta-Peptides - biosynthesis</subject><subject>Amyloid beta-Protein Precursor - metabolism</subject><subject>Amyloid Precursor Protein Secretases - metabolism</subject><subject>Beta-amyloid</subject><subject>Biomarkers - metabolism</subject><subject>Brain - enzymology</subject><subject>Brain - pathology</subject><subject>Brain - physiopathology</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Disease Progression</subject><subject>Down Syndrome - enzymology</subject><subject>Down Syndrome - pathology</subject><subject>Down Syndrome - physiopathology</subject><subject>Female</subject><subject>Humans</subject><subject>Infant</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Oldest old</subject><subject>Plaque, Amyloid - enzymology</subject><subject>Plaque, Amyloid - pathology</subject><subject>Reference Values</subject><subject>Trisomy 21</subject><subject>Up-Regulation - physiology</subject><issn>0197-4580</issn><issn>1558-1497</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNklGL1DAQx4so3t7pV5A8iG9dkyZNWpCD4_RO4cAH9TlMk-leapusSbvSb2_LLp7ni8LAEPKb_0zynyx7zeiWUSbfdluPUwyNCz3snN9tC0rldo2CP8k2rCyrnIlaPc02lNUqF2VFz7LzlDpKqRJKPs_OmKypKATfZN1Vv7-HnIC3pMER8oQmLjkhATO6gxtnAokAaSe_nIMnoSWww4cCGOY-OEucJ-_DT0_S7G0Mw5HwIQ7QkyaC8y-yZy30CV-e8kX27ebD1-uP-d3n20_XV3e5kaIcc7C8glLWKFRVg6W2QMal4Fiykhslma25ooVojRBlI1to20IZsKbFSqCi_CK7POrup2ZAa9CPEXq9j26AOOsATj--8e5e78JBc67KiotF4M1JIIYfE6ZRDy4Z7HvwGKakZcUqsQzzT5DVXNayKBfw3RE0MaQUsf09DaN6dVV3-rGrenVVr1GsfV79-aKH4pONC3BzBHD514PDqJNx6A1aF9GM2gb3v50u_xIyvfPOQP8dZ0xdmKJfvNNMp0JT_WXdsHXBqKRLeSH5LwAE0wY</recordid><startdate>20071001</startdate><enddate>20071001</enddate><creator>Nistor, M</creator><creator>Don, M</creator><creator>Parekh, M</creator><creator>Sarsoza, F</creator><creator>Goodus, M</creator><creator>Lopez, G.E</creator><creator>Kawas, C</creator><creator>Leverenz, J</creator><creator>Doran, E</creator><creator>Lott, I.T</creator><creator>Hill, M</creator><creator>Head, E</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20071001</creationdate><title>Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain</title><author>Nistor, M ; Don, M ; Parekh, M ; Sarsoza, F ; Goodus, M ; Lopez, G.E ; Kawas, C ; Leverenz, J ; Doran, E ; Lott, I.T ; Hill, M ; Head, E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c645t-ad38a569e4789ad0d2e13643e5153c761d937024fc445b6faff27cadcfe84e703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aging - metabolism</topic><topic>Aging - pathology</topic><topic>Alzheimer's disease</topic><topic>Amyloid beta-Peptides - biosynthesis</topic><topic>Amyloid beta-Protein Precursor - metabolism</topic><topic>Amyloid Precursor Protein Secretases - metabolism</topic><topic>Beta-amyloid</topic><topic>Biomarkers - metabolism</topic><topic>Brain - enzymology</topic><topic>Brain - pathology</topic><topic>Brain - physiopathology</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Disease Progression</topic><topic>Down Syndrome - enzymology</topic><topic>Down Syndrome - pathology</topic><topic>Down Syndrome - physiopathology</topic><topic>Female</topic><topic>Humans</topic><topic>Infant</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Oldest old</topic><topic>Plaque, Amyloid - enzymology</topic><topic>Plaque, Amyloid - pathology</topic><topic>Reference Values</topic><topic>Trisomy 21</topic><topic>Up-Regulation - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nistor, M</creatorcontrib><creatorcontrib>Don, M</creatorcontrib><creatorcontrib>Parekh, M</creatorcontrib><creatorcontrib>Sarsoza, F</creatorcontrib><creatorcontrib>Goodus, M</creatorcontrib><creatorcontrib>Lopez, G.E</creatorcontrib><creatorcontrib>Kawas, C</creatorcontrib><creatorcontrib>Leverenz, J</creatorcontrib><creatorcontrib>Doran, E</creatorcontrib><creatorcontrib>Lott, I.T</creatorcontrib><creatorcontrib>Hill, M</creatorcontrib><creatorcontrib>Head, E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neurobiology of aging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nistor, M</au><au>Don, M</au><au>Parekh, M</au><au>Sarsoza, F</au><au>Goodus, M</au><au>Lopez, G.E</au><au>Kawas, C</au><au>Leverenz, J</au><au>Doran, E</au><au>Lott, I.T</au><au>Hill, M</au><au>Head, E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain</atitle><jtitle>Neurobiology of aging</jtitle><addtitle>Neurobiol Aging</addtitle><date>2007-10-01</date><risdate>2007</risdate><volume>28</volume><issue>10</issue><spage>1493</spage><epage>1506</epage><pages>1493-1506</pages><issn>0197-4580</issn><eissn>1558-1497</eissn><abstract>Abstract Aged individuals with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by the age of 40 years. The purpose of the current study was to measure age-associated changes in APP processing in 36 individuals with DS (5 months–69 years) and in 26 controls (5 months–100 years). Alpha-secretase significantly decreased with age in DS, particularly in cases over the age of 40 years and was stable in controls. The levels of C-terminal fragments of APP reflecting alpha-secretase processing (CTF-alpha) decreased with age in both groups. In both groups, there was significant increase in beta-secretase activity with age. CTF-beta remained constant with age in controls suggesting compensatory increases in turnover/clearance mechanisms. In DS, young individuals had the lowest CTF-beta levels that may reflect rapid conversion of beta-amyloid (Aβ) to soluble pools or efficient CTF-beta clearance mechanisms. Treatments to slow or prevent AD in the general population targeting secretase activity may be more efficacious in adults with DS if combined with approaches that enhance Aβ degradation and clearance.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>16904243</pmid><doi>10.1016/j.neurobiolaging.2006.06.023</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Aging - metabolism Aging - pathology Alzheimer's disease Amyloid beta-Peptides - biosynthesis Amyloid beta-Protein Precursor - metabolism Amyloid Precursor Protein Secretases - metabolism Beta-amyloid Biomarkers - metabolism Brain - enzymology Brain - pathology Brain - physiopathology Child Child, Preschool Disease Progression Down Syndrome - enzymology Down Syndrome - pathology Down Syndrome - physiopathology Female Humans Infant Internal Medicine Male Middle Aged Neurology Oldest old Plaque, Amyloid - enzymology Plaque, Amyloid - pathology Reference Values Trisomy 21 Up-Regulation - physiology |
| title | Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain |
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