Cerebrospinal fluid Aβ42 levels and APP processing pathway genes in Parkinson's disease
Background Of recent interest is the finding that certain cerebrospinal fluid (CSF) biomarkers traditionally linked to Alzheimer's disease (AD), specifically amyloid beta protein (Aβ), are abnormal in PD CSF. The aim of this exploratory investigation was to determine whether genetic variation w...
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| Veröffentlicht in: | Movement disorders 2015-06, Vol.30 (7), p.936-944 |
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| creator | Bekris, Lynn M. Tsuang, Debby W. Peskind, Elaine R. Yu, Chang E. Montine, Thomas J. Zhang, Jing Zabetian, Cyrus P. Leverenz, James B. |
| description | Background
Of recent interest is the finding that certain cerebrospinal fluid (CSF) biomarkers traditionally linked to Alzheimer's disease (AD), specifically amyloid beta protein (Aβ), are abnormal in PD CSF. The aim of this exploratory investigation was to determine whether genetic variation within the amyloid precursor protein (APP) processing pathway genes correlates with CSF Aβ42 levels in Parkinson's disease (PD).
Methods
Parkinson's disease (n = 86) and control (n = 161) DNA were genotyped for 19 regulatory region tagging single‐nucleotide polymorphisms (SNPs) within nine genes (APP, ADAM10, BACE1, BACE2, PSEN1, PSEN2, PEN2, NCSTN, and APH1B) involved in the cleavage of APP. The SNP genotypes were tested for their association with CSF biomarkers and PD risk while adjusting for age, sex, and APOE ɛ4 status.
Results
Significant correlation with CSF Aβ42 levels in PD was observed for two SNPs, (APP rs466448 and APH1B rs2068143). Conversely, significant correlation with CSF Aβ42 levels in controls was observed for three SNPs (APP rs214484, rs2040273, and PSEN1 rs362344).
Conclusions
In addition, results of this exploratory investigation suggest that an APP SNP and an APH1B SNP are marginally associated with PD CSF Aβ42 levels in APOE ɛ4 noncarriers. Further hypotheses generated include that decreased CSF Aβ42 levels are in part driven by genetic variation in APP processing genes. Additional investigation into the relationship between these findings and clinical characteristics of PD, including cognitive impairment, compared with other neurodegenerative diseases, such as AD, are warranted. © 2015 International Parkinson and Movement Disorder Society |
| doi_str_mv | 10.1002/mds.26172 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4478197</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1691012562</sourcerecordid><originalsourceid>FETCH-LOGICAL-i2942-285db6b6c475b3264016b50d6321a7e6b078507bfd0d95f8f0ce016e4346f7ff3</originalsourceid><addsrcrecordid>eNpVUc1O3DAQtlARbCmHvkDlW3sJeOz4J5dKaOlCJSirAgL1YjnJZHHrddJ4F7qv1QfpMzWwdEVPM5r5fqTvI-QtsANgjB_O63TAFWi-RUYgBWSGS_2KjJgxMhNg5C55ndJ3xgAkqB2yy6VhphDFiNyOsceyb1Pnowu0CUtf06M_v3NOA95jSNTF4TCd0q5vK0zJxxnt3OLuwa3oDCMm6iOduv6Hj6mN7xOtfUKX8A3ZblxIuP8898j15NPV-DQ7uzj5PD46yzwvcp5xI-tSlarKtSwFVzkDVUpWK8HBaVQl00YyXTY1qwvZmIZVOEAwF7lqdNOIPfJxrdstyznWFcZF74Ltej93_cq2ztv_P9Hf2Vl7b_NcGyj0IPDhWaBvfy4xLezcpwpDcBHbZbKgCmDApeID9N1Lr43JvzgHwOEa8OADrjZ_YPaxJzv0ZJ96sufHl0_LwMjWDJ8W-GvDGPK0Sgst7c2XEzuZfD0tbr-BVeIvprqVRw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1691012562</pqid></control><display><type>article</type><title>Cerebrospinal fluid Aβ42 levels and APP processing pathway genes in Parkinson's disease</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Bekris, Lynn M. ; Tsuang, Debby W. ; Peskind, Elaine R. ; Yu, Chang E. ; Montine, Thomas J. ; Zhang, Jing ; Zabetian, Cyrus P. ; Leverenz, James B.</creator><creatorcontrib>Bekris, Lynn M. ; Tsuang, Debby W. ; Peskind, Elaine R. ; Yu, Chang E. ; Montine, Thomas J. ; Zhang, Jing ; Zabetian, Cyrus P. ; Leverenz, James B.</creatorcontrib><description>Background
Of recent interest is the finding that certain cerebrospinal fluid (CSF) biomarkers traditionally linked to Alzheimer's disease (AD), specifically amyloid beta protein (Aβ), are abnormal in PD CSF. The aim of this exploratory investigation was to determine whether genetic variation within the amyloid precursor protein (APP) processing pathway genes correlates with CSF Aβ42 levels in Parkinson's disease (PD).
Methods
Parkinson's disease (n = 86) and control (n = 161) DNA were genotyped for 19 regulatory region tagging single‐nucleotide polymorphisms (SNPs) within nine genes (APP, ADAM10, BACE1, BACE2, PSEN1, PSEN2, PEN2, NCSTN, and APH1B) involved in the cleavage of APP. The SNP genotypes were tested for their association with CSF biomarkers and PD risk while adjusting for age, sex, and APOE ɛ4 status.
Results
Significant correlation with CSF Aβ42 levels in PD was observed for two SNPs, (APP rs466448 and APH1B rs2068143). Conversely, significant correlation with CSF Aβ42 levels in controls was observed for three SNPs (APP rs214484, rs2040273, and PSEN1 rs362344).
Conclusions
In addition, results of this exploratory investigation suggest that an APP SNP and an APH1B SNP are marginally associated with PD CSF Aβ42 levels in APOE ɛ4 noncarriers. Further hypotheses generated include that decreased CSF Aβ42 levels are in part driven by genetic variation in APP processing genes. Additional investigation into the relationship between these findings and clinical characteristics of PD, including cognitive impairment, compared with other neurodegenerative diseases, such as AD, are warranted. © 2015 International Parkinson and Movement Disorder Society</description><identifier>ISSN: 0885-3185</identifier><identifier>EISSN: 1531-8257</identifier><identifier>DOI: 10.1002/mds.26172</identifier><identifier>PMID: 25808939</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>ADAM10 ; Aged ; Aged, 80 and over ; Amyloid beta-Peptides - cerebrospinal fluid ; Amyloid beta-Protein Precursor - genetics ; Amyloid Precursor Protein Secretases - genetics ; APH1B ; Apolipoprotein E4 - genetics ; APP ; BACE1 ; BACE2 ; Biomarkers - cerebrospinal fluid ; cerebrospinal fluid ; Female ; Humans ; Male ; Middle Aged ; NCSTN ; Parkinson Disease - cerebrospinal fluid ; Parkinson Disease - genetics ; Parkinson's disease ; PEN2 ; Peptide Fragments - cerebrospinal fluid ; Polymorphism, Single Nucleotide ; PSEN1 ; PSEN2</subject><ispartof>Movement disorders, 2015-06, Vol.30 (7), p.936-944</ispartof><rights>2015 International Parkinson and Movement Disorder Society</rights><rights>2015 International Parkinson and Movement Disorder Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fmds.26172$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fmds.26172$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25808939$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bekris, Lynn M.</creatorcontrib><creatorcontrib>Tsuang, Debby W.</creatorcontrib><creatorcontrib>Peskind, Elaine R.</creatorcontrib><creatorcontrib>Yu, Chang E.</creatorcontrib><creatorcontrib>Montine, Thomas J.</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Zabetian, Cyrus P.</creatorcontrib><creatorcontrib>Leverenz, James B.</creatorcontrib><title>Cerebrospinal fluid Aβ42 levels and APP processing pathway genes in Parkinson's disease</title><title>Movement disorders</title><addtitle>Mov Disord</addtitle><description>Background
Of recent interest is the finding that certain cerebrospinal fluid (CSF) biomarkers traditionally linked to Alzheimer's disease (AD), specifically amyloid beta protein (Aβ), are abnormal in PD CSF. The aim of this exploratory investigation was to determine whether genetic variation within the amyloid precursor protein (APP) processing pathway genes correlates with CSF Aβ42 levels in Parkinson's disease (PD).
Methods
Parkinson's disease (n = 86) and control (n = 161) DNA were genotyped for 19 regulatory region tagging single‐nucleotide polymorphisms (SNPs) within nine genes (APP, ADAM10, BACE1, BACE2, PSEN1, PSEN2, PEN2, NCSTN, and APH1B) involved in the cleavage of APP. The SNP genotypes were tested for their association with CSF biomarkers and PD risk while adjusting for age, sex, and APOE ɛ4 status.
Results
Significant correlation with CSF Aβ42 levels in PD was observed for two SNPs, (APP rs466448 and APH1B rs2068143). Conversely, significant correlation with CSF Aβ42 levels in controls was observed for three SNPs (APP rs214484, rs2040273, and PSEN1 rs362344).
Conclusions
In addition, results of this exploratory investigation suggest that an APP SNP and an APH1B SNP are marginally associated with PD CSF Aβ42 levels in APOE ɛ4 noncarriers. Further hypotheses generated include that decreased CSF Aβ42 levels are in part driven by genetic variation in APP processing genes. Additional investigation into the relationship between these findings and clinical characteristics of PD, including cognitive impairment, compared with other neurodegenerative diseases, such as AD, are warranted. © 2015 International Parkinson and Movement Disorder Society</description><subject>ADAM10</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Amyloid beta-Peptides - cerebrospinal fluid</subject><subject>Amyloid beta-Protein Precursor - genetics</subject><subject>Amyloid Precursor Protein Secretases - genetics</subject><subject>APH1B</subject><subject>Apolipoprotein E4 - genetics</subject><subject>APP</subject><subject>BACE1</subject><subject>BACE2</subject><subject>Biomarkers - cerebrospinal fluid</subject><subject>cerebrospinal fluid</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>NCSTN</subject><subject>Parkinson Disease - cerebrospinal fluid</subject><subject>Parkinson Disease - genetics</subject><subject>Parkinson's disease</subject><subject>PEN2</subject><subject>Peptide Fragments - cerebrospinal fluid</subject><subject>Polymorphism, Single Nucleotide</subject><subject>PSEN1</subject><subject>PSEN2</subject><issn>0885-3185</issn><issn>1531-8257</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUc1O3DAQtlARbCmHvkDlW3sJeOz4J5dKaOlCJSirAgL1YjnJZHHrddJ4F7qv1QfpMzWwdEVPM5r5fqTvI-QtsANgjB_O63TAFWi-RUYgBWSGS_2KjJgxMhNg5C55ndJ3xgAkqB2yy6VhphDFiNyOsceyb1Pnowu0CUtf06M_v3NOA95jSNTF4TCd0q5vK0zJxxnt3OLuwa3oDCMm6iOduv6Hj6mN7xOtfUKX8A3ZblxIuP8898j15NPV-DQ7uzj5PD46yzwvcp5xI-tSlarKtSwFVzkDVUpWK8HBaVQl00YyXTY1qwvZmIZVOEAwF7lqdNOIPfJxrdstyznWFcZF74Ltej93_cq2ztv_P9Hf2Vl7b_NcGyj0IPDhWaBvfy4xLezcpwpDcBHbZbKgCmDApeID9N1Lr43JvzgHwOEa8OADrjZ_YPaxJzv0ZJ96sufHl0_LwMjWDJ8W-GvDGPK0Sgst7c2XEzuZfD0tbr-BVeIvprqVRw</recordid><startdate>201506</startdate><enddate>201506</enddate><creator>Bekris, Lynn M.</creator><creator>Tsuang, Debby W.</creator><creator>Peskind, Elaine R.</creator><creator>Yu, Chang E.</creator><creator>Montine, Thomas J.</creator><creator>Zhang, Jing</creator><creator>Zabetian, Cyrus P.</creator><creator>Leverenz, James B.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201506</creationdate><title>Cerebrospinal fluid Aβ42 levels and APP processing pathway genes in Parkinson's disease</title><author>Bekris, Lynn M. ; Tsuang, Debby W. ; Peskind, Elaine R. ; Yu, Chang E. ; Montine, Thomas J. ; Zhang, Jing ; Zabetian, Cyrus P. ; Leverenz, James B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i2942-285db6b6c475b3264016b50d6321a7e6b078507bfd0d95f8f0ce016e4346f7ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>ADAM10</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Amyloid beta-Peptides - cerebrospinal fluid</topic><topic>Amyloid beta-Protein Precursor - genetics</topic><topic>Amyloid Precursor Protein Secretases - genetics</topic><topic>APH1B</topic><topic>Apolipoprotein E4 - genetics</topic><topic>APP</topic><topic>BACE1</topic><topic>BACE2</topic><topic>Biomarkers - cerebrospinal fluid</topic><topic>cerebrospinal fluid</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>NCSTN</topic><topic>Parkinson Disease - cerebrospinal fluid</topic><topic>Parkinson Disease - genetics</topic><topic>Parkinson's disease</topic><topic>PEN2</topic><topic>Peptide Fragments - cerebrospinal fluid</topic><topic>Polymorphism, Single Nucleotide</topic><topic>PSEN1</topic><topic>PSEN2</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bekris, Lynn M.</creatorcontrib><creatorcontrib>Tsuang, Debby W.</creatorcontrib><creatorcontrib>Peskind, Elaine R.</creatorcontrib><creatorcontrib>Yu, Chang E.</creatorcontrib><creatorcontrib>Montine, Thomas J.</creatorcontrib><creatorcontrib>Zhang, Jing</creatorcontrib><creatorcontrib>Zabetian, Cyrus P.</creatorcontrib><creatorcontrib>Leverenz, James B.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Movement disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bekris, Lynn M.</au><au>Tsuang, Debby W.</au><au>Peskind, Elaine R.</au><au>Yu, Chang E.</au><au>Montine, Thomas J.</au><au>Zhang, Jing</au><au>Zabetian, Cyrus P.</au><au>Leverenz, James B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cerebrospinal fluid Aβ42 levels and APP processing pathway genes in Parkinson's disease</atitle><jtitle>Movement disorders</jtitle><addtitle>Mov Disord</addtitle><date>2015-06</date><risdate>2015</risdate><volume>30</volume><issue>7</issue><spage>936</spage><epage>944</epage><pages>936-944</pages><issn>0885-3185</issn><eissn>1531-8257</eissn><abstract>Background
Of recent interest is the finding that certain cerebrospinal fluid (CSF) biomarkers traditionally linked to Alzheimer's disease (AD), specifically amyloid beta protein (Aβ), are abnormal in PD CSF. The aim of this exploratory investigation was to determine whether genetic variation within the amyloid precursor protein (APP) processing pathway genes correlates with CSF Aβ42 levels in Parkinson's disease (PD).
Methods
Parkinson's disease (n = 86) and control (n = 161) DNA were genotyped for 19 regulatory region tagging single‐nucleotide polymorphisms (SNPs) within nine genes (APP, ADAM10, BACE1, BACE2, PSEN1, PSEN2, PEN2, NCSTN, and APH1B) involved in the cleavage of APP. The SNP genotypes were tested for their association with CSF biomarkers and PD risk while adjusting for age, sex, and APOE ɛ4 status.
Results
Significant correlation with CSF Aβ42 levels in PD was observed for two SNPs, (APP rs466448 and APH1B rs2068143). Conversely, significant correlation with CSF Aβ42 levels in controls was observed for three SNPs (APP rs214484, rs2040273, and PSEN1 rs362344).
Conclusions
In addition, results of this exploratory investigation suggest that an APP SNP and an APH1B SNP are marginally associated with PD CSF Aβ42 levels in APOE ɛ4 noncarriers. Further hypotheses generated include that decreased CSF Aβ42 levels are in part driven by genetic variation in APP processing genes. Additional investigation into the relationship between these findings and clinical characteristics of PD, including cognitive impairment, compared with other neurodegenerative diseases, such as AD, are warranted. © 2015 International Parkinson and Movement Disorder Society</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>25808939</pmid><doi>10.1002/mds.26172</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Movement disorders, 2015-06, Vol.30 (7), p.936-944 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | ADAM10 Aged Aged, 80 and over Amyloid beta-Peptides - cerebrospinal fluid Amyloid beta-Protein Precursor - genetics Amyloid Precursor Protein Secretases - genetics APH1B Apolipoprotein E4 - genetics APP BACE1 BACE2 Biomarkers - cerebrospinal fluid cerebrospinal fluid Female Humans Male Middle Aged NCSTN Parkinson Disease - cerebrospinal fluid Parkinson Disease - genetics Parkinson's disease PEN2 Peptide Fragments - cerebrospinal fluid Polymorphism, Single Nucleotide PSEN1 PSEN2 |
| title | Cerebrospinal fluid Aβ42 levels and APP processing pathway genes in Parkinson's disease |
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