APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study
Deposition of amyloid-β (Aβ) in the cerebral cortex is thought to be a pivotal event in Alzheimer’s disease (AD) pathogenesis with a significant genetic contribution. Molecular imaging can provide an early noninvasive phenotype, but small samples have prohibited genome-wide association studies (GWAS...
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| Veröffentlicht in: | Molecular psychiatry 2014-03, Vol.19 (3), p.351-357 |
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| creator | Ramanan, V K Risacher, S L Nho, K Kim, S Swaminathan, S Shen, L Foroud, T M Hakonarson, H Huentelman, M J Aisen, P S Petersen, R C Green, R C Jack, C R Koeppe, R A Jagust, W J Weiner, M W Saykin, A J |
| description | Deposition of amyloid-β (Aβ) in the cerebral cortex is thought to be a pivotal event in Alzheimer’s disease (AD) pathogenesis with a significant genetic contribution. Molecular imaging can provide an early noninvasive phenotype, but small samples have prohibited genome-wide association studies (GWAS) of cortical Aβ load until now. We employed florbetapir (
18
F) positron emission tomography (PET) imaging to assess brain Aβ levels
in vivo
for 555 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). More than six million common genetic variants were tested for association to quantitative global cortical Aβ load controlling for age, gender and diagnosis. Independent genome-wide significant associations were identified on chromosome 19 within
APOE
(apolipoprotein E) (rs429358,
P
=5.5 × 10
−14
) and on chromosome 3 upstream of
BCHE
(butyrylcholinesterase) (rs509208,
P
=2.7 × 10
−8
) in a region previously associated with serum BCHE activity. Together, these loci explained 15% of the variance in cortical Aβ levels in this sample (
APOE
10.7%,
BCHE
4.3%). Suggestive associations were identified within
ITGA6
, near
EFNA5
,
EDIL3
,
ITGA1
,
PIK3R1
,
NFIB
and
ARID1B
, and between
NUAK1
and
C12orf75
. These results confirm the association of
APOE
with Aβ deposition and represent the largest known effect of
BCHE
on an AD-related phenotype. BCHE has been found in senile plaques and this new association of genetic variation at the
BCHE
locus with Aβ burden in humans may have implications for potential disease-modifying effects of BCHE-modulating agents in the AD spectrum. |
| doi_str_mv | 10.1038/mp.2013.19 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3661739</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A362607601</galeid><sourcerecordid>A362607601</sourcerecordid><originalsourceid>FETCH-LOGICAL-c666t-e145aca52e7f73d2c6e40d9874a640e01aa0080322fdfab0c6966ca8c3a386393</originalsourceid><addsrcrecordid>eNqNkk2LFDEQhhtR3HX04g-QgAii9Jjv7vYgjMPoCgu7h_UcapL0mLU7mU26lfn3pp1xP1REckiReuot6k0VxVOC5wSz-k2_nVNM2Jw094pjwitZClHV93PMRFNyUvOj4lFKlxhPSfGwOKKMk6Zm5Lj4ujg_WyHwBr1fnuQgoT6YsYMhxIRCi7SNdh2hQ9DvuuAMMnYbkhtc8G8RoLYLcW0H2LqIzlcXaGN96G353RmbtVLQDiYUpWE0u8fFgxa6ZJ8c7lnx-cPqYnlSnp59_LRcnJZaSjmUlnABGgS1VVsxQ7W0HJumrjhIji0mABjXmFHamhbWWMtGSg21ZsBqyRo2K97tdbfjurdGWz_kCdQ2uh7iTgVw6m7Guy9qE74pJiWpfgq8PAjEcDXaNKjeJW27DrwNY1JEUJ4NFIL9B5p_psI1mdDnv6GXYYw-O6Go5KKSDeX_pLIWrhjlgt9QG-iscr4NeRA9tVYLJqnElcx9Z8X8L1Q-xvZOB29bl9_vFLzaF-gYUoq2vTaNYDXtmuq3ato1RSaXnt22-Rr9tVwZeHEAIGno2gheu3TD1ZTQmtHMvd5zKaf8xsZbI__Z9gdjwucT</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1500732454</pqid></control><display><type>article</type><title>APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Ramanan, V K ; Risacher, S L ; Nho, K ; Kim, S ; Swaminathan, S ; Shen, L ; Foroud, T M ; Hakonarson, H ; Huentelman, M J ; Aisen, P S ; Petersen, R C ; Green, R C ; Jack, C R ; Koeppe, R A ; Jagust, W J ; Weiner, M W ; Saykin, A J</creator><creatorcontrib>Ramanan, V K ; Risacher, S L ; Nho, K ; Kim, S ; Swaminathan, S ; Shen, L ; Foroud, T M ; Hakonarson, H ; Huentelman, M J ; Aisen, P S ; Petersen, R C ; Green, R C ; Jack, C R ; Koeppe, R A ; Jagust, W J ; Weiner, M W ; Saykin, A J ; Alzheimer’s Disease Neuroimaging Initiative ; for the Alzheimer’s Disease Neuroimaging Initiative</creatorcontrib><description>Deposition of amyloid-β (Aβ) in the cerebral cortex is thought to be a pivotal event in Alzheimer’s disease (AD) pathogenesis with a significant genetic contribution. Molecular imaging can provide an early noninvasive phenotype, but small samples have prohibited genome-wide association studies (GWAS) of cortical Aβ load until now. We employed florbetapir (
18
F) positron emission tomography (PET) imaging to assess brain Aβ levels
in vivo
for 555 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). More than six million common genetic variants were tested for association to quantitative global cortical Aβ load controlling for age, gender and diagnosis. Independent genome-wide significant associations were identified on chromosome 19 within
APOE
(apolipoprotein E) (rs429358,
P
=5.5 × 10
−14
) and on chromosome 3 upstream of
BCHE
(butyrylcholinesterase) (rs509208,
P
=2.7 × 10
−8
) in a region previously associated with serum BCHE activity. Together, these loci explained 15% of the variance in cortical Aβ levels in this sample (
APOE
10.7%,
BCHE
4.3%). Suggestive associations were identified within
ITGA6
, near
EFNA5
,
EDIL3
,
ITGA1
,
PIK3R1
,
NFIB
and
ARID1B
, and between
NUAK1
and
C12orf75
. These results confirm the association of
APOE
with Aβ deposition and represent the largest known effect of
BCHE
on an AD-related phenotype. BCHE has been found in senile plaques and this new association of genetic variation at the
BCHE
locus with Aβ burden in humans may have implications for potential disease-modifying effects of BCHE-modulating agents in the AD spectrum.</description><identifier>ISSN: 1359-4184</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/mp.2013.19</identifier><identifier>PMID: 23419831</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/1647/2217/2138 ; 631/208/726/649 ; 692/699/375/365/1283 ; Adult and adolescent clinical studies ; Aged ; Aged, 80 and over ; Alzheimer Disease - genetics ; Alzheimer's disease ; Amyloid beta-protein ; Aniline Compounds ; Apolipoprotein E ; Apolipoproteins ; Apolipoproteins E - genetics ; Behavioral Sciences ; Biological and medical sciences ; Biological Psychology ; Butyrylcholinesterase - genetics ; Cerebral cortex ; Cerebral Cortex - diagnostic imaging ; Cerebral Cortex - metabolism ; Chromosome 19 ; Chromosome 3 ; Cognitive Dysfunction - genetics ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Ethylene Glycols ; Female ; Functional Neuroimaging ; Genetic diversity ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genomics ; Genotype & phenotype ; Geriatrics ; Humans ; Male ; Medical imaging ; Medical sciences ; Medicine ; Medicine & Public Health ; Middle Aged ; Neurodegenerative diseases ; Neuroimaging ; Neurology ; Neuromodulation ; Neurosciences ; Organic mental disorders. Neuropsychology ; original-article ; Pharmacotherapy ; Phenotypes ; Physiological aspects ; Plaque, Amyloid - diagnostic imaging ; Plaque, Amyloid - metabolism ; Positron emission tomography ; Psychiatric research ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Senile plaques ; Tomography ; White People - genetics ; β-Amyloid</subject><ispartof>Molecular psychiatry, 2014-03, Vol.19 (3), p.351-357</ispartof><rights>Macmillan Publishers Limited 2014</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2014 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Mar 2014</rights><rights>Macmillan Publishers Limited 2014.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c666t-e145aca52e7f73d2c6e40d9874a640e01aa0080322fdfab0c6966ca8c3a386393</citedby><cites>FETCH-LOGICAL-c666t-e145aca52e7f73d2c6e40d9874a640e01aa0080322fdfab0c6966ca8c3a386393</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28212832$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23419831$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ramanan, V K</creatorcontrib><creatorcontrib>Risacher, S L</creatorcontrib><creatorcontrib>Nho, K</creatorcontrib><creatorcontrib>Kim, S</creatorcontrib><creatorcontrib>Swaminathan, S</creatorcontrib><creatorcontrib>Shen, L</creatorcontrib><creatorcontrib>Foroud, T M</creatorcontrib><creatorcontrib>Hakonarson, H</creatorcontrib><creatorcontrib>Huentelman, M J</creatorcontrib><creatorcontrib>Aisen, P S</creatorcontrib><creatorcontrib>Petersen, R C</creatorcontrib><creatorcontrib>Green, R C</creatorcontrib><creatorcontrib>Jack, C R</creatorcontrib><creatorcontrib>Koeppe, R A</creatorcontrib><creatorcontrib>Jagust, W J</creatorcontrib><creatorcontrib>Weiner, M W</creatorcontrib><creatorcontrib>Saykin, A J</creatorcontrib><creatorcontrib>Alzheimer’s Disease Neuroimaging Initiative</creatorcontrib><creatorcontrib>for the Alzheimer’s Disease Neuroimaging Initiative</creatorcontrib><title>APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><addtitle>Mol Psychiatry</addtitle><description>Deposition of amyloid-β (Aβ) in the cerebral cortex is thought to be a pivotal event in Alzheimer’s disease (AD) pathogenesis with a significant genetic contribution. Molecular imaging can provide an early noninvasive phenotype, but small samples have prohibited genome-wide association studies (GWAS) of cortical Aβ load until now. We employed florbetapir (
18
F) positron emission tomography (PET) imaging to assess brain Aβ levels
in vivo
for 555 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). More than six million common genetic variants were tested for association to quantitative global cortical Aβ load controlling for age, gender and diagnosis. Independent genome-wide significant associations were identified on chromosome 19 within
APOE
(apolipoprotein E) (rs429358,
P
=5.5 × 10
−14
) and on chromosome 3 upstream of
BCHE
(butyrylcholinesterase) (rs509208,
P
=2.7 × 10
−8
) in a region previously associated with serum BCHE activity. Together, these loci explained 15% of the variance in cortical Aβ levels in this sample (
APOE
10.7%,
BCHE
4.3%). Suggestive associations were identified within
ITGA6
, near
EFNA5
,
EDIL3
,
ITGA1
,
PIK3R1
,
NFIB
and
ARID1B
, and between
NUAK1
and
C12orf75
. These results confirm the association of
APOE
with Aβ deposition and represent the largest known effect of
BCHE
on an AD-related phenotype. BCHE has been found in senile plaques and this new association of genetic variation at the
BCHE
locus with Aβ burden in humans may have implications for potential disease-modifying effects of BCHE-modulating agents in the AD spectrum.</description><subject>631/1647/2217/2138</subject><subject>631/208/726/649</subject><subject>692/699/375/365/1283</subject><subject>Adult and adolescent clinical studies</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alzheimer Disease - genetics</subject><subject>Alzheimer's disease</subject><subject>Amyloid beta-protein</subject><subject>Aniline Compounds</subject><subject>Apolipoprotein E</subject><subject>Apolipoproteins</subject><subject>Apolipoproteins E - genetics</subject><subject>Behavioral Sciences</subject><subject>Biological and medical sciences</subject><subject>Biological Psychology</subject><subject>Butyrylcholinesterase - genetics</subject><subject>Cerebral cortex</subject><subject>Cerebral Cortex - diagnostic imaging</subject><subject>Cerebral Cortex - metabolism</subject><subject>Chromosome 19</subject><subject>Chromosome 3</subject><subject>Cognitive Dysfunction - genetics</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Ethylene Glycols</subject><subject>Female</subject><subject>Functional Neuroimaging</subject><subject>Genetic diversity</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Genotype & phenotype</subject><subject>Geriatrics</subject><subject>Humans</subject><subject>Male</subject><subject>Medical imaging</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Neurodegenerative diseases</subject><subject>Neuroimaging</subject><subject>Neurology</subject><subject>Neuromodulation</subject><subject>Neurosciences</subject><subject>Organic mental disorders. Neuropsychology</subject><subject>original-article</subject><subject>Pharmacotherapy</subject><subject>Phenotypes</subject><subject>Physiological aspects</subject><subject>Plaque, Amyloid - diagnostic imaging</subject><subject>Plaque, Amyloid - metabolism</subject><subject>Positron emission tomography</subject><subject>Psychiatric research</subject><subject>Psychiatry</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Senile plaques</subject><subject>Tomography</subject><subject>White People - genetics</subject><subject>β-Amyloid</subject><issn>1359-4184</issn><issn>1476-5578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkk2LFDEQhhtR3HX04g-QgAii9Jjv7vYgjMPoCgu7h_UcapL0mLU7mU26lfn3pp1xP1REckiReuot6k0VxVOC5wSz-k2_nVNM2Jw094pjwitZClHV93PMRFNyUvOj4lFKlxhPSfGwOKKMk6Zm5Lj4ujg_WyHwBr1fnuQgoT6YsYMhxIRCi7SNdh2hQ9DvuuAMMnYbkhtc8G8RoLYLcW0H2LqIzlcXaGN96G353RmbtVLQDiYUpWE0u8fFgxa6ZJ8c7lnx-cPqYnlSnp59_LRcnJZaSjmUlnABGgS1VVsxQ7W0HJumrjhIji0mABjXmFHamhbWWMtGSg21ZsBqyRo2K97tdbfjurdGWz_kCdQ2uh7iTgVw6m7Guy9qE74pJiWpfgq8PAjEcDXaNKjeJW27DrwNY1JEUJ4NFIL9B5p_psI1mdDnv6GXYYw-O6Go5KKSDeX_pLIWrhjlgt9QG-iscr4NeRA9tVYLJqnElcx9Z8X8L1Q-xvZOB29bl9_vFLzaF-gYUoq2vTaNYDXtmuq3ato1RSaXnt22-Rr9tVwZeHEAIGno2gheu3TD1ZTQmtHMvd5zKaf8xsZbI__Z9gdjwucT</recordid><startdate>20140301</startdate><enddate>20140301</enddate><creator>Ramanan, V K</creator><creator>Risacher, S L</creator><creator>Nho, K</creator><creator>Kim, S</creator><creator>Swaminathan, S</creator><creator>Shen, L</creator><creator>Foroud, T M</creator><creator>Hakonarson, H</creator><creator>Huentelman, M J</creator><creator>Aisen, P S</creator><creator>Petersen, R C</creator><creator>Green, R C</creator><creator>Jack, C R</creator><creator>Koeppe, R A</creator><creator>Jagust, W J</creator><creator>Weiner, M W</creator><creator>Saykin, A J</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</scope><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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140301</creationdate><title>APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study</title><author>Ramanan, V K ; Risacher, S L ; Nho, K ; Kim, S ; Swaminathan, S ; Shen, L ; Foroud, T M ; Hakonarson, H ; Huentelman, M J ; Aisen, P S ; Petersen, R C ; Green, R C ; Jack, C R ; Koeppe, R A ; Jagust, W J ; Weiner, M W ; Saykin, A J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c666t-e145aca52e7f73d2c6e40d9874a640e01aa0080322fdfab0c6966ca8c3a386393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>631/1647/2217/2138</topic><topic>631/208/726/649</topic><topic>692/699/375/365/1283</topic><topic>Adult and adolescent clinical studies</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alzheimer Disease - genetics</topic><topic>Alzheimer's disease</topic><topic>Amyloid beta-protein</topic><topic>Aniline Compounds</topic><topic>Apolipoprotein E</topic><topic>Apolipoproteins</topic><topic>Apolipoproteins E - genetics</topic><topic>Behavioral Sciences</topic><topic>Biological and medical sciences</topic><topic>Biological Psychology</topic><topic>Butyrylcholinesterase - genetics</topic><topic>Cerebral cortex</topic><topic>Cerebral Cortex - diagnostic imaging</topic><topic>Cerebral Cortex - metabolism</topic><topic>Chromosome 19</topic><topic>Chromosome 3</topic><topic>Cognitive Dysfunction - genetics</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Ethylene Glycols</topic><topic>Female</topic><topic>Functional Neuroimaging</topic><topic>Genetic diversity</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Genotype & phenotype</topic><topic>Geriatrics</topic><topic>Humans</topic><topic>Male</topic><topic>Medical imaging</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Neurodegenerative diseases</topic><topic>Neuroimaging</topic><topic>Neurology</topic><topic>Neuromodulation</topic><topic>Neurosciences</topic><topic>Organic mental disorders. Neuropsychology</topic><topic>original-article</topic><topic>Pharmacotherapy</topic><topic>Phenotypes</topic><topic>Physiological aspects</topic><topic>Plaque, Amyloid - diagnostic imaging</topic><topic>Plaque, Amyloid - metabolism</topic><topic>Positron emission tomography</topic><topic>Psychiatric research</topic><topic>Psychiatry</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Senile plaques</topic><topic>Tomography</topic><topic>White People - genetics</topic><topic>β-Amyloid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ramanan, V K</creatorcontrib><creatorcontrib>Risacher, S L</creatorcontrib><creatorcontrib>Nho, K</creatorcontrib><creatorcontrib>Kim, S</creatorcontrib><creatorcontrib>Swaminathan, S</creatorcontrib><creatorcontrib>Shen, L</creatorcontrib><creatorcontrib>Foroud, T M</creatorcontrib><creatorcontrib>Hakonarson, H</creatorcontrib><creatorcontrib>Huentelman, M J</creatorcontrib><creatorcontrib>Aisen, P S</creatorcontrib><creatorcontrib>Petersen, R C</creatorcontrib><creatorcontrib>Green, R C</creatorcontrib><creatorcontrib>Jack, C R</creatorcontrib><creatorcontrib>Koeppe, R A</creatorcontrib><creatorcontrib>Jagust, W J</creatorcontrib><creatorcontrib>Weiner, M W</creatorcontrib><creatorcontrib>Saykin, A J</creatorcontrib><creatorcontrib>Alzheimer’s Disease Neuroimaging Initiative</creatorcontrib><creatorcontrib>for the Alzheimer’s Disease Neuroimaging Initiative</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ramanan, V K</au><au>Risacher, S L</au><au>Nho, K</au><au>Kim, S</au><au>Swaminathan, S</au><au>Shen, L</au><au>Foroud, T M</au><au>Hakonarson, H</au><au>Huentelman, M J</au><au>Aisen, P S</au><au>Petersen, R C</au><au>Green, R C</au><au>Jack, C R</au><au>Koeppe, R A</au><au>Jagust, W J</au><au>Weiner, M W</au><au>Saykin, A J</au><aucorp>Alzheimer’s Disease Neuroimaging Initiative</aucorp><aucorp>for the Alzheimer’s Disease Neuroimaging Initiative</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study</atitle><jtitle>Molecular psychiatry</jtitle><stitle>Mol Psychiatry</stitle><addtitle>Mol Psychiatry</addtitle><date>2014-03-01</date><risdate>2014</risdate><volume>19</volume><issue>3</issue><spage>351</spage><epage>357</epage><pages>351-357</pages><issn>1359-4184</issn><eissn>1476-5578</eissn><abstract>Deposition of amyloid-β (Aβ) in the cerebral cortex is thought to be a pivotal event in Alzheimer’s disease (AD) pathogenesis with a significant genetic contribution. Molecular imaging can provide an early noninvasive phenotype, but small samples have prohibited genome-wide association studies (GWAS) of cortical Aβ load until now. We employed florbetapir (
18
F) positron emission tomography (PET) imaging to assess brain Aβ levels
in vivo
for 555 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). More than six million common genetic variants were tested for association to quantitative global cortical Aβ load controlling for age, gender and diagnosis. Independent genome-wide significant associations were identified on chromosome 19 within
APOE
(apolipoprotein E) (rs429358,
P
=5.5 × 10
−14
) and on chromosome 3 upstream of
BCHE
(butyrylcholinesterase) (rs509208,
P
=2.7 × 10
−8
) in a region previously associated with serum BCHE activity. Together, these loci explained 15% of the variance in cortical Aβ levels in this sample (
APOE
10.7%,
BCHE
4.3%). Suggestive associations were identified within
ITGA6
, near
EFNA5
,
EDIL3
,
ITGA1
,
PIK3R1
,
NFIB
and
ARID1B
, and between
NUAK1
and
C12orf75
. These results confirm the association of
APOE
with Aβ deposition and represent the largest known effect of
BCHE
on an AD-related phenotype. BCHE has been found in senile plaques and this new association of genetic variation at the
BCHE
locus with Aβ burden in humans may have implications for potential disease-modifying effects of BCHE-modulating agents in the AD spectrum.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>23419831</pmid><doi>10.1038/mp.2013.19</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1359-4184 |
| ispartof | Molecular psychiatry, 2014-03, Vol.19 (3), p.351-357 |
| issn | 1359-4184 1476-5578 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3661739 |
| source | MEDLINE; Alma/SFX Local Collection |
| subjects | 631/1647/2217/2138 631/208/726/649 692/699/375/365/1283 Adult and adolescent clinical studies Aged Aged, 80 and over Alzheimer Disease - genetics Alzheimer's disease Amyloid beta-protein Aniline Compounds Apolipoprotein E Apolipoproteins Apolipoproteins E - genetics Behavioral Sciences Biological and medical sciences Biological Psychology Butyrylcholinesterase - genetics Cerebral cortex Cerebral Cortex - diagnostic imaging Cerebral Cortex - metabolism Chromosome 19 Chromosome 3 Cognitive Dysfunction - genetics Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Ethylene Glycols Female Functional Neuroimaging Genetic diversity Genome-wide association studies Genome-Wide Association Study Genomes Genomics Genotype & phenotype Geriatrics Humans Male Medical imaging Medical sciences Medicine Medicine & Public Health Middle Aged Neurodegenerative diseases Neuroimaging Neurology Neuromodulation Neurosciences Organic mental disorders. Neuropsychology original-article Pharmacotherapy Phenotypes Physiological aspects Plaque, Amyloid - diagnostic imaging Plaque, Amyloid - metabolism Positron emission tomography Psychiatric research Psychiatry Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Senile plaques Tomography White People - genetics β-Amyloid |
| title | APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-12T02%3A25%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=APOE%20and%20BCHE%20as%20modulators%20of%20cerebral%20amyloid%20deposition:%20a%20florbetapir%20PET%20genome-wide%20association%20study&rft.jtitle=Molecular%20psychiatry&rft.au=Ramanan,%20V%20K&rft.aucorp=Alzheimer%E2%80%99s%20Disease%20Neuroimaging%20Initiative&rft.date=2014-03-01&rft.volume=19&rft.issue=3&rft.spage=351&rft.epage=357&rft.pages=351-357&rft.issn=1359-4184&rft.eissn=1476-5578&rft_id=info:doi/10.1038/mp.2013.19&rft_dat=%3Cgale_pubme%3EA362607601%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1500732454&rft_id=info:pmid/23419831&rft_galeid=A362607601&rfr_iscdi=true |