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Article ; Online: Multiple insulin degrading enzyme variants alter in vitro reporter gene expression.

Belbin, Olivia / Crump, Michael / Bisceglio, Gina D / Carrasquillo, Minerva M / Morgan, Kevin / Younkin, Steven G

PloS one

2011 Volume 6, Issue 6, Page(s) e21429

Abstract: The insulin degrading enzyme (IDE) variant, v311 (rs6583817), is associated with increased post-mortem cerebellar IDE mRNA, decreased plasma β-amyloid (Aβ), decreased risk for Alzheimer's disease (AD) and increased reporter gene expression, suggesting ... ...

Abstract	The insulin degrading enzyme (IDE) variant, v311 (rs6583817), is associated with increased post-mortem cerebellar IDE mRNA, decreased plasma β-amyloid (Aβ), decreased risk for Alzheimer's disease (AD) and increased reporter gene expression, suggesting that it is a functional variant driving increased IDE expression. To identify other functional IDE variants, we have tested v685, rs11187061 (associated with decreased cerebellar IDE mRNA) and variants on H6, the haplotype tagged by v311 (v10; rs4646958, v315; rs7895832, v687; rs17107734 and v154; rs4646957), for altered in vitro reporter gene expression. The reporter gene expression levels associated with the second most common haplotype (H2) successfully replicated the post-mortem findings in hepatocytoma (0.89 fold-change, p = 0.04) but not neuroblastoma cells. Successful in vitro replication was achieved for H6 in neuroblastoma cells when the sequence was cloned 5' to the promoter (1.18 fold-change, p = 0.006) and 3' to the reporter gene (1.29 fold change, p = 0.003), an effect contributed to by four variants (v10, v315, v154 and v311). Since IDE mediates Aβ degradation, variants that regulate IDE expression could represent good therapeutic targets for AD.
MeSH term(s)	Base Sequence ; Cell Line, Tumor ; Gene Expression ; Genes, Reporter/genetics ; Haplotypes/genetics ; Humans ; Insulysin/genetics ; Luciferases/genetics ; Polymorphism, Single Nucleotide/genetics
Chemical Substances	Luciferases (EC 1.13.12.-) ; Insulysin (EC 3.4.24.56)
Language	English
Publishing date	2011-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0021429
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Article ; Online: Evaluating pathogenic dementia variants in posterior cortical atrophy.

Carrasquillo, Minerva M / Barber, Imelda / Lincoln, Sarah J / Murray, Melissa E / Camsari, Gamze Balci / Khan, Qurat Ul Ain / Nguyen, Thuy / Ma, Li / Bisceglio, Gina D / Crook, Julia E / Younkin, Steven G / Dickson, Dennis W / Boeve, Bradley F / Graff-Radford, Neill R / Morgan, Kevin / Ertekin-Taner, Nilüfer

Neurobiology of aging

2016 Volume 37, Page(s) 38–44

Abstract: Posterior cortical atrophy (PCA) is an understudied visual impairment syndrome most often due to "posterior Alzheimer's disease (AD)" pathology. Case studies detected mutations in PSEN1, PSEN2, GRN, MAPT, and PRNP in subjects with clinical PCA. To detect ...

Abstract	Posterior cortical atrophy (PCA) is an understudied visual impairment syndrome most often due to "posterior Alzheimer's disease (AD)" pathology. Case studies detected mutations in PSEN1, PSEN2, GRN, MAPT, and PRNP in subjects with clinical PCA. To detect the frequency and spectrum of mutations in known dementia genes in PCA, we screened 124 European-American subjects with clinical PCA (n = 67) or posterior AD neuropathology (n = 57) for variants in genes implicated in AD, frontotemporal dementia, and prion disease using NeuroX, a customized exome array. Frequencies in PCA of the variants annotated as pathogenic or potentially pathogenic were compared against ∼ 4300 European-American population controls from the NHLBI Exome Sequencing Project. We identified 2 rare variants not previously reported in PCA, TREM2 Arg47His, and PSEN2 Ser130Leu. No other pathogenic or potentially pathogenic variants were detected in the screened dementia genes. In this first systematic variant screen of a PCA cohort, we report 2 rare mutations in TREM2 and PSEN2, validate our previously reported APOE ε4 association, and demonstrate the utility of NeuroX.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Alzheimer Disease/genetics ; Cohort Studies ; Exome/genetics ; Female ; Genotype ; Genotyping Techniques/methods ; Humans ; Male ; Membrane Glycoproteins/genetics ; Middle Aged ; Mutation ; Presenilin-2/genetics ; Receptors, Immunologic/genetics ; Syndrome ; Vision Disorders/genetics
Chemical Substances	Membrane Glycoproteins ; PSEN2 protein, human ; Presenilin-2 ; Receptors, Immunologic ; TREM2 protein, human
Language	English
Publishing date	2016-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604505-4
ISSN	1558-1497 ; 0197-4580
ISSN (online)	1558-1497
ISSN	0197-4580
DOI	10.1016/j.neurobiolaging.2015.09.023
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Article ; Online: Linking protective GAB2 variants, increased cortical GAB2 expression and decreased Alzheimer's disease pathology.

Zou, Fanggeng / Belbin, Olivia / Carrasquillo, Minerva M / Culley, Oliver J / Hunter, Talisha A / Ma, Li / Bisceglio, Gina D / Allen, Mariet / Dickson, Dennis W / Graff-Radford, Neill R / Petersen, Ronald C / Morgan, Kevin / Younkin, Steven G

PloS one

2013 Volume 8, Issue 5, Page(s) e64802

Abstract: GRB-associated binding protein 2 (GAB2) represents a compelling genome-wide association signal for late-onset Alzheimer's disease (LOAD) with reported odds ratios (ORs) ranging from 0.75-0.85. We tested eight GAB2 variants in four North American ... ...

Abstract	GRB-associated binding protein 2 (GAB2) represents a compelling genome-wide association signal for late-onset Alzheimer's disease (LOAD) with reported odds ratios (ORs) ranging from 0.75-0.85. We tested eight GAB2 variants in four North American Caucasian case-control series (2,316 LOAD, 2,538 controls) for association with LOAD. Meta-analyses revealed ORs ranging from (0.61-1.20) with no significant association (all p>0.32). Four variants were hetergeneous across the populations (all p<0.02) due to a potentially inflated effect size (OR = 0.61-0.66) only observed in the smallest series (702 LOAD, 209 controls). Despite the lack of association in our series, the previously reported protective association for GAB2 remained after meta-analyses of our data with all available previously published series (11,952-22,253 samples; OR = 0.82-0.88; all p<0.04). Using a freely available database of lymphoblastoid cell lines we found that protective GAB2 variants were associated with increased GAB2 expression (p = 9.5×10(-7)-9.3×10(-6)). We next measured GAB2 mRNA levels in 249 brains and found that decreased neurofibrillary tangle (r = -0.34, p = 0.0006) and senile plaque counts (r = -0.32, p = 0.001) were both good predictors of increased GAB2 mRNA levels albeit that sex (r = -0.28, p = 0.005) may have been a contributing factor. In summary, we hypothesise that GAB2 variants that are protective against LOAD in some populations may act functionally to increase GAB2 mRNA levels (in lymphoblastoid cells) and that increased GAB2 mRNA levels are associated with significantly decreased LOAD pathology. These findings support the hypothesis that Gab2 may protect neurons against LOAD but due to significant population heterogeneity, it is still unclear whether this protection is detectable at the genetic level.
MeSH term(s)	Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Aged ; Alzheimer Disease/genetics ; Alzheimer Disease/pathology ; Apolipoproteins E/genetics ; Case-Control Studies ; Cell Line ; Epistasis, Genetic ; Female ; Genetic Association Studies ; Genetic Heterogeneity ; Genetic Loci/genetics ; Genetic Predisposition to Disease ; Haplotypes/genetics ; Humans ; Male ; Meta-Analysis as Topic ; North America ; Polymorphism, Single Nucleotide/genetics ; Postmortem Changes ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Risk Factors ; Temporal Lobe/metabolism ; Temporal Lobe/pathology
Chemical Substances	Adaptor Proteins, Signal Transducing ; Apolipoproteins E ; GAB2 protein, human ; RNA, Messenger
Language	English
Publishing date	2013-05-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0064802
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Article ; Online: TMEM106B risk variant is implicated in the pathologic presentation of Alzheimer disease.

Rutherford, Nicola J / Carrasquillo, Minerva M / Li, Ma / Bisceglio, Gina / Menke, Joshua / Josephs, Keith A / Parisi, Joseph E / Petersen, Ronald C / Graff-Radford, Neill R / Younkin, Steven G / Dickson, Dennis W / Rademakers, Rosa

Neurology

2012 Volume 79, Issue 7, Page(s) 717–718

MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; DNA-Binding Proteins/metabolism ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Gliosis/genetics ; Gliosis/metabolism ; Gliosis/pathology ; Hippocampus/metabolism ; Hippocampus/pathology ; Humans ; Male ; Membrane Proteins/genetics ; Nerve Tissue Proteins/genetics ; Neurons/metabolism ; Neurons/pathology ; Sclerosis
Chemical Substances	DNA-Binding Proteins ; Membrane Proteins ; Nerve Tissue Proteins ; TMEM106B protein, human
Language	English
Publishing date	2012-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0b013e318264e3ac
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Article ; Online: Late-onset Alzheimer disease genetic variants in posterior cortical atrophy and posterior AD.

Carrasquillo, Minerva M / Khan, Qurat ul Ain / Murray, Melissa E / Krishnan, Siddharth / Aakre, Jeremiah / Pankratz, V Shane / Nguyen, Thuy / Ma, Li / Bisceglio, Gina / Petersen, Ronald C / Younkin, Steven G / Dickson, Dennis W / Boeve, Bradley F / Graff-Radford, Neill R / Ertekin-Taner, Nilüfer

Neurology

2014 Volume 82, Issue 16, Page(s) 1455–1462

Abstract: Objective: To investigate association of genetic risk factors for late-onset Alzheimer disease (LOAD) with risk of posterior cortical atrophy (PCA), a syndrome of visual impairment with predominant Alzheimer disease (AD) pathology in posterior cortical ... ...

Abstract	Objective: To investigate association of genetic risk factors for late-onset Alzheimer disease (LOAD) with risk of posterior cortical atrophy (PCA), a syndrome of visual impairment with predominant Alzheimer disease (AD) pathology in posterior cortical regions, and with risk of "posterior AD" neuropathology. Methods: We assessed 81 participants with PCA diagnosed clinically and 54 with neuropathologic diagnosis of posterior AD vs 2,523 controls for association with 11 significant single nucleotide polymorphisms (SNPs) from published LOAD risk genome-wide association studies. Results: There was highly significant association with APOE ε4 and increased risk of PCA (p = 0.0003, odds ratio [OR] = 3.17) and posterior AD (p = 1.11 × 10(-17), OR = 6.43). No other locus was significant after corrections for multiple testing, although rs11136000 near CLU (p = 0.019, OR = 0.60) and rs744373 near BIN1 (p = 0.025, OR = 1. 63) associated nominally significantly with posterior AD, and rs3851179 at the PICALM locus had significant association with PCA (p = 0.0003, OR = 2.84). ABCA7 locus SNP rs3764650, which was also tested under the recessive model because of Hardy-Weinberg disequilibrium, also had nominally significant association with PCA risk. The direction of association at APOE, CLU, and BIN1 loci was the same for participants with PCA and posterior AD. The effects for all SNPs, except rs3851179, were consistent with those for LOAD risk. Conclusions: We identified a significant effect for APOE and nominate CLU, BIN1, and ABCA7 as additional risk loci for PCA and posterior AD. Our findings suggest that at least some of the genetic risk factors for LOAD are shared with these atypical conditions and provide effect-size estimates for their future genetic studies.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/diagnosis ; Alzheimer Disease/epidemiology ; Alzheimer Disease/genetics ; Atrophy ; Cerebral Cortex/pathology ; Cerebral Ventricles/pathology ; Comorbidity ; Cross-Sectional Studies ; Female ; Genetic Variation/genetics ; Humans ; Male ; Neurologic Examination ; Neuropsychological Tests ; Sweden ; Tomography, X-Ray Computed
Language	English
Publishing date	2014-03-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000000335
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Article ; Online: ABCA7 Deficiency Accelerates Amyloid-β Generation and Alzheimer's Neuronal Pathology.

The Journal of neuroscience : the official journal of the Society for Neuroscience

2016 Volume 36, Issue 13, Page(s) 3848–3859

Abstract: In Alzheimer's disease (AD), the accumulation and deposition of amyloid-β (Aβ) peptides in the brain is a central event. Aβ is cleaved from amyloid precursor protein (APP) by β-secretase and γ-secretase mainly in neurons. Although mutations inAPP,PS1, ... ...

Abstract	In Alzheimer's disease (AD), the accumulation and deposition of amyloid-β (Aβ) peptides in the brain is a central event. Aβ is cleaved from amyloid precursor protein (APP) by β-secretase and γ-secretase mainly in neurons. Although mutations inAPP,PS1, orPS2cause early-onset familial AD,ABCA7encoding ATP-binding cassette transporter A7 is one of the susceptibility genes for late-onset AD (LOAD), in which itsloss-of-functionvariants increase the disease risk. ABCA7 is homologous to a major lipid transporter ABCA1 and is highly expressed in neurons and microglia in the brain. Here, we show that ABCA7 deficiency altered brain lipid profile and impaired memory in ABCA7 knock-out (Abca7(-/-)) mice. When bred to amyloid model APP/PS1 mice, plaque burden was exacerbated by ABCA7 deficit.In vivomicrodialysis studies indicated that the clearance rate of Aβ was unaltered. Interestingly, ABCA7 deletion facilitated the processing of APP to Aβ by increasing the levels of β-site APP cleaving enzyme 1 (BACE1) and sterol regulatory element-binding protein 2 (SREBP2) in primary neurons and mouse brains. Knock-down of ABCA7 expression in neurons caused endoplasmic reticulum stress highlighted by increased level of protein kinase R-like endoplasmic reticulum kinase (PERK) and increased phosphorylation of eukaryotic initiation factor 2α (eIF2α). In the brains of APP/PS1;Abca7(-/-)mice, the level of phosphorylated extracellular regulated kinase (ERK) was also significantly elevated. Together, our results reveal novel pathways underlying the association of ABCA7 dysfunction and LOAD pathogenesis. Significance statement: Gene variants inABCA7encoding ATP-binding cassette transporter A7 are associated with the increased risk for late-onset Alzheimer's disease (AD). Importantly, we found the altered brain lipid profile and impaired memory in ABCA7 knock-out mice. The accumulation of amyloid-β (Aβ) peptides cleaved from amyloid precursor protein (APP) in the brain is a key event in AD pathogenesis and we also found that ABCA7 deficit exacerbated brain Aβ deposition in amyloid AD model APP/PS1 mice. Mechanistically, we found that ABCA7 deletion facilitated the processing of APP and Aβ production by increasing the levels of β-secretase 1 (BACE1) in primary neurons and mouse brains without affecting the Aβ clearance rate in APP/PS1 mice. Our study demonstrates a novel mechanism underlying how dysfunctions of ABCA7 contribute to the risk for AD.
MeSH term(s)	ATP-Binding Cassette Transporters/deficiency ; ATP-Binding Cassette Transporters/genetics ; ATP-Binding Cassette Transporters/metabolism ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/genetics ; Animals ; Brain/metabolism ; Brain/pathology ; Disease Models, Animal ; Eukaryotic Initiation Factor-2/metabolism ; Female ; Gene Expression Regulation/genetics ; Humans ; Lipid Metabolism/genetics ; Male ; Memory Disorders/genetics ; Mice ; Mice, Transgenic ; Mutation/genetics ; Presenilin-1/genetics ; Signal Transduction/genetics
Chemical Substances	ATP-Binding Cassette Transporters ; Abca7 protein, mouse ; Abce1 protein, mouse ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Eukaryotic Initiation Factor-2 ; Presenilin-1
Language	English
Publishing date	2016-03-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.3757-15.2016
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Article: Investigation of 15 of the top candidate genes for late-onset Alzheimer's disease

Belbin, Olivia / Carrasquillo, Minerva M / Crump, Michael / Culley, Oliver J / Hunter, Talisha A / Ma, Li / Bisceglio, Gina / Zou, Fanggeng / Allen, Mariet / Dickson, Dennis W / Graff-Radford, Neill R / Petersen, Ronald C / Morgan, Kevin / Younkin, Steven G

Human genetics. 2011 Mar., v. 129, no. 3

2011

Abstract: The 12 genome-wide association studies (GWAS) published to-date for late-onset Alzheimer's disease (LOAD) have identified over 40 candidate LOAD risk modifiers, in addition to apolipoprotein (APOE) ε4. A few of these novel LOAD candidate genes, namely ... ...

Abstract	The 12 genome-wide association studies (GWAS) published to-date for late-onset Alzheimer's disease (LOAD) have identified over 40 candidate LOAD risk modifiers, in addition to apolipoprotein (APOE) ε4. A few of these novel LOAD candidate genes, namely BIN1, CLU, CR1, EXOC3L2 and PICALM, have shown consistent replication, and are thus credible LOAD susceptibility genes. To evaluate other promising LOAD candidate genes, we have added data from our large, case-control series (n = 5,043) to meta-analyses of all published follow-up case-control association studies for six LOAD candidate genes that have shown significant association across multiple studies (TNK1, GAB2, LOC651924, GWA_14q32.13, PGBD1 and GALP) and for an additional nine previously suggested candidate genes. Meta-analyses remained significant at three loci after addition of our data: GAB2 (OR = 0.78, p = 0.007), LOC651924 (OR = 0.91, p = 0.01) and TNK1 (OR = 0.92, p = 0.02). Breslow-Day tests revealed significant heterogeneity between studies for GAB2 (p < 0.0001) and GWA_14q32.13 (p = 0.006). We have also provided suggestive evidence that PGBD1 (p = 0.04) and EBF3 (p = 0.03) are associated with age-at-onset of LOAD. Finally, we tested for interactions between these 15 genes, APOE ε4 and the five novel LOAD genes BIN1, CLU, CR1, EXOC3L2 and PICALM but none were significant after correction for multiple testing. Overall, this large, independent follow-up study for 15 of the top LOAD candidate genes provides support for GAB2 and LOC651924 (6q24.1) as risk modifiers of LOAD and novel associations between PGBD1 and EBF3 with age-at-onset.
Language	English
Dates of publication	2011-03
Size	p. 273-282.
Publisher	Springer-Verlag
Publishing place	Berlin/Heidelberg
Document type	Article
ZDB-ID	223009-4
ISSN	1432-1203 ; 0340-6717
ISSN (online)	1432-1203
ISSN	0340-6717
DOI	10.1007/s00439-010-0924-2
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Genetically-controlled Vesicle-Associated Membrane Protein 1 expression may contribute to Alzheimer's pathophysiology and susceptibility.

Sevlever, Daniel / Zou, Fanggeng / Ma, Li / Carrasquillo, Sebastian / Crump, Michael G / Culley, Oliver J / Hunter, Talisha A / Bisceglio, Gina D / Younkin, Linda / Allen, Mariet / Carrasquillo, Minerva M / Sando, Sigrid B / Aasly, Jan O / Dickson, Dennis W / Graff-Radford, Neill R / Petersen, Ronald C / Deák, Ferenc / Belbin, Olivia

Molecular neurodegeneration

2015 Volume 10, Page(s) 18

Abstract: Background: Alzheimer's disease is a neurodegenerative disorder in which extracellular deposition of β-amyloid (Aβ) oligomers causes synaptic injury resulting in early memory loss, altered homeostasis, accumulation of hyperphosphorylated tau and cell ... ...

Abstract	Background: Alzheimer's disease is a neurodegenerative disorder in which extracellular deposition of β-amyloid (Aβ) oligomers causes synaptic injury resulting in early memory loss, altered homeostasis, accumulation of hyperphosphorylated tau and cell death. Since proteins in the SNAP (Soluble N-ethylmaleimide-sensitive factor Attachment Protein) REceptors (SNARE) complex are essential for neuronal Aβ release at pre-synaptic terminals, we hypothesized that genetically controlled SNARE expression could alter neuronal Aß release at the synapse and hence play an early role in Alzheimer's pathophysiology. Results: Here we report 5 polymorphisms in Vesicle-Associated Membrane Protein 1 (VAMP1), a gene encoding a member of the SNARE complex, associated with bidirectionally altered cerebellar VAMP1 transcript levels (all p<0.05). At the functional level, we demonstrated that control of VAMP1 expression by heterogeneous knockdown in mice resulted in up to 74% reduction in neuronal Aβ exocytosis (p<0.001). We performed a case-control association study of the 5 VAMP1 expression regulating polymorphisms in 4,667 Alzheimer's disease patients and 6,175 controls to determine their contribution to Alzheimer's disease risk. We found that polymorphisms associated with increased brain VAMP1 transcript levels conferred higher risk for Alzheimer's disease than those associated with lower VAMP1 transcript levels (p=0.03). Moreover, we also report a modest protective association for a common VAMP1 polymorphism with Alzheimer's disease risk (OR=0.88, p=0.03). This polymorphism was associated with decreased VAMP1 transcript levels (p=0.02) and was functionally active in a dual luciferase reporter gene assay (p<0.01). Conclusions: Genetically regulated VAMP1 expression in the brain may modify both Alzheimer's disease risk and may contribute to Alzheimer's pathophysiology.
MeSH term(s)	Alzheimer Disease/genetics ; Alzheimer Disease/physiopathology ; Amyloid beta-Peptides/genetics ; Amyloid beta-Peptides/metabolism ; Animals ; Genetic Predisposition to Disease ; Genetic Testing ; Humans ; Mice ; Synapses/metabolism ; Vesicle-Associated Membrane Protein 1/genetics ; Vesicle-Associated Membrane Protein 1/metabolism
Chemical Substances	Amyloid beta-Peptides ; Vesicle-Associated Membrane Protein 1
Language	English
Publishing date	2015-04-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1750-1326
ISSN (online)	1750-1326
DOI	10.1186/s13024-015-0015-x
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Article ; Online: Erratum to: Genetically-controlled Vesicle-Associated Membrane Protein 1 expression may contribute to Alzheimer's pathophysiology and susceptibility.

Molecular neurodegeneration

2015 Volume 10, Page(s) 49

Abstract: Following publication of this work, we noticed that we inadvertently failed to include Dr Ferenc Deák in the author list. The author list has now been corrected and the amended authors' contributions section has been modified accordingly below. ...

Abstract	Following publication of this work, we noticed that we inadvertently failed to include Dr Ferenc Deák in the author list. The author list has now been corrected and the amended authors' contributions section has been modified accordingly below.
Language	English
Publishing date	2015-09-23
Publishing country	England
Document type	Published Erratum
ISSN	1750-1326
ISSN (online)	1750-1326
DOI	10.1186/s13024-015-0047-2
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Article ; Online: Replication of CLU, CR1, and PICALM associations with alzheimer disease.

Carrasquillo, Minerva M / Belbin, Olivia / Hunter, Talisha A / Ma, Li / Bisceglio, Gina D / Zou, Fanggeng / Crook, Julia E / Pankratz, V Shane / Dickson, Dennis W / Graff-Radford, Neill R / Petersen, Ronald C / Morgan, Kevin / Younkin, Steven G

Archives of neurology

2010 Volume 67, Issue 8, Page(s) 961–964

Abstract: Objective: To test for replication of the association between variants in the CLU, CR1, and PICALM genes with Alzheimer disease.: Design: Follow-up case-control association study.: Setting: The Mayo Clinics at Jacksonville, Florida, and Rochester, ...

Abstract	Objective: To test for replication of the association between variants in the CLU, CR1, and PICALM genes with Alzheimer disease. Design: Follow-up case-control association study. Setting: The Mayo Clinics at Jacksonville, Florida, and Rochester, Minnesota. Participants: Community-based patients of European descent with late-onset Alzheimer disease (LOAD) and controls without dementia who were seen at the Mayo clinics, and autopsy-confirmed cases and controls whose pathology was evaluated at the Mayo Clinic in Jacksonville. Additional samples were obtained from the National Cell Repository for Alzheimer Disease (NCRAD). A total of 1829 LOAD cases and 2576 controls were analyzed. Interventions: The most significant single-nucleotide polymorphisms in CLU (rs11136000), CR1 (rs3818361), and PICALM (rs3851179) were tested for allelic association with LOAD. Main Outcome Measure Clinical or pathology-confirmed diagnosis of LOAD. Results: Odds ratios for CLU, CR1, and PICALM were 0.82, 1.15, and 0.80, respectively, comparable in direction and magnitude with those originally reported. P values were 8.6 x 10(-5), .014, and 1.3 x 10(-5), respectively; they remain significant even after Bonferroni correction for the 3 single-nucleotide polymorphisms tested. Conclusion: These results show near-perfect replication and provide the first additional evidence that CLU, CR1, and PICALM are associated with the risk of LOAD.
MeSH term(s)	Alzheimer Disease/genetics ; Alzheimer Disease/pathology ; Case-Control Studies ; Clusterin/genetics ; European Continental Ancestry Group ; Follow-Up Studies ; Gene Frequency ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Humans ; Monomeric Clathrin Assembly Proteins/genetics ; Odds Ratio ; Polymorphism, Single Nucleotide/genetics ; Receptors, Complement 3b/genetics ; Residence Characteristics
Chemical Substances	CLU protein, human ; CR1 protein, human ; Clusterin ; Monomeric Clathrin Assembly Proteins ; PICALM protein, human ; Receptors, Complement 3b
Language	English
Publishing date	2010-06-14
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80049-1
ISSN	1538-3687 ; 0003-9942
ISSN (online)	1538-3687
ISSN	0003-9942
DOI	10.1001/archneurol.2010.147
Database	MEDical Literature Analysis and Retrieval System OnLINE

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