- Email: [email protected]
RELATIONSHIP BETWEEN APOLIPOPROTEIN E4 GENOTYPE AND WHOLE BODY AEROBIC CAPACITY
P646 P2-093
Poster Presentations: Monday, July 25, 2016 POLYMORPHISM IN CYTOCHROME P450 GENE IS ASSOCIATED WITH ALZHEIMER’S PATHOLOGY
Andrea Lessa Benedet1, Lei Yu2, Aurelie Labbe3, Sulantha S. Mathotaarachchi4, Monica Shin4,5, Tharick A. Pascoal5, Min-Su Kang6, Thomas Beaudry7, Serge Gauthier4, David A. Bennett2, Pedro Rosa-Neto4,5,8, 1Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Montreal, QC, Canada; 2 Rush University Medical Center, Chicago, IL, USA; 3McGill University, Montreal, QC, Canada; 4McGill University Research Centre for Studies in Aging, Verdun, QC, Canada; 5Translational Neuroimaging Laboratory-McGill University, Verdun, QC, Canada; 6Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging-McGill University, Montreal, QC, Canada; 7McGill Centre for Studies in Aging, Montreal, QC, Canada; 8Douglas Hospital Research Centre, Verdun, QC, Canada. Contact e-mail: tharick.alipascoal@mail. mcgill.ca Background: The cytochromes P450 (CYP) are known for their role
in metabolizing several endogenous and exogenous substrates. In the brain, they modulate blood-flow regulation, metabolize cholesterol, and participate in neuroinflammatory processes. CYP activity is also implicated in Alzheimer’s disease (AD), particularly in amyloid-b (Ab) accumulation in CSF. We examined whether genetic polymorphisms of CYP are associated with AD pathology. Methods: [18F]florbetapir-PET imaging was employed to assess brain Ab levels in 256 subjects from a discovery cohort (ADNI: 186CN, 105 lMCI, 47AD). Linear regression models examined the association of 30 SNPs from four genes of CYP (CYP3A4, CYP2C9, CYP2C19 and CYP1A1) with global [18F]florbetapirSUVR, adjusting for age, sex, and ApoE-e4carriage status. Significant signals were interrogated at the voxel level using RMINCtool, and, separately, tested for associations with CSF Ab and Ab/p-tau ratio. Neuropathologic data from the Rush ROS and MAP cohorts were used to generalize the findings to Ab load and PHFtau tangle density by immunocytochemistry in post-mortem brains (302 CN, 180 aMCI, 259 AD). Results: The analysis of [18F]florbetapir identified an intronic variant in the CYP2C19 gene (rs4388808; P¼0.0005), in which carriers of the minor-allele (G) had lower global SUVR (Figure 1). The voxel-wise analysis showed a significant effect of the SNP in the frontal and posterior cingulate cortices, as well as in the inferior parietal cortex (Figure 2). Carriers of the minor-allele were also associated with higher
Figure 2. Voxel-wise comparison between minor allele non-carriers(-) and carriers(+) of the polymorphism rs4388808 of CYP2C19. A significant difference was observed in the frontal and posterior cingulate cortices, as well as in the inferior parietal cortex. The voxel-wise analysis was adjusted for age, gender and ApoE-e4 carriage status.
CSF Ab (P¼0.003) and higher Ab/p-tau ratio (P¼0.01). In postmortem brains, minor-allele carriers had a lower Ab load (P¼0.04), lower PHFtau tangle density (P¼0.03) as well as better episodic memory (P¼0.008). Conclusions: The rs4388808, an intronic variant of the CYP2C19 gene is implicated in Ab load, tau pathology and episodic memory, where the minor-allele protects against AD pathology.
P2-094
RELATIONSHIP BETWEEN APOLIPOPROTEIN E4 GENOTYPE AND WHOLE BODY AEROBIC CAPACITY
Jill K. Morris, Eric D. Vidoni, Heather M. Wilkins, Russell H. Swerdlow, Jeffrey M. Burns, University of Kansas Alzheimer’s Disease Center, Fairway, KS, USA. Contact e-mail: [email protected] Background: Apolipoprotein e4, the primary risk gene for sporadic
Figure 1. Comparison between non-carriers(-) and carriers(+) of the minor allele of rs4388808 (CYP2C19). A significant difference was observed in brain amyloid load (A), CSF Ab levels (B) and CSF Ab/p-tau ratio (C) using ADNI cohort. Results were generalized using post-mortem data from Rush ROS and MAP cohorts, where a concordant pattern was observed in amyloid load (D), PHF-tau tangle density (E) and episodic memory scores (F). The linear models were adjusted for age, gender and ApoE-e4 carriage status.
Alzheimer’s Disease (AD), has been demonstrated to elicit detrimental effects on cellular respiration in preclinical models. However, the relationship between whole body aerobic capacity (VO2 max) and apolipoprotein e4 genotype is unclear. We sought to examine the effect of APOE e4 genotype on aerobic capacity. Methods: We enrolled 154 elderly subjects with either no dementia (ND; n¼98) or Alzheimer’s disease (AD; n¼57) in this study. All subjects underwent genotyping for APOE e4 and cardiopulmonary exercise testing. A staff exercise physiologist led the exercise test. Following a medical screen to determine cardiac risk, a modified Cornell Bruce protocol was used during treadmill exercise. Results: Diagnosis groups did not differ in age. As expected, a higher frequency of APOE e4 carriers was observed in the AD group (31, 54%) compared to the ND group (21, 21%; p<0.001). There was a main effect of APOE e4 genotype on VO2 max (p¼0.003), with APOE e4 carriers exhibiting lower VO2 max compared to APOE e4 non-carriers. VO2max did not differ by diagnosis group, and no interaction effect was observed. Conclusions: These results
Poster Presentations: Monday, July 25, 2016
support a potential effect of apolipoprotein e4 on whole body aerobic capacity in human subjects and warrant further research into potential mechanisms.
P2-095
SORL1 IS GENETICALLY ASSOCIATED WITH ALZHEIMER’S DISEASE IN HAN CHINESE
Jong-Ling Fuh1,2, Yi-Chu Liao1,2, Wei-Ju Lee2,3, Yen-Feng Wang1,2, ShihPin Chen1,2, Shuu-Jiun Wang1,2, 1Taipei Veterans General Hospital, Taipei, Taiwan; 2National Yang-Ming University Schools of Medicine, Taipei, Taiwan; 3Taichung Veterans General Hospital, Taichung, Taiwan. Contact e-mail: [email protected] Background: The recycling of the amyloid precursor protein via the
endocytic pathway plays an important role in regulating the generation of amyloid b. The neuronal sortilin-related receptor gene Table 1 Demographic data N (%) or mean 6 SD
Controls (N ¼ 401)
MCI cases (N ¼ 157)
AD cases (N ¼ 798)
Age (y) Male (%) Education (y) MMSE score 12-item word recall test Forward digit span Backward digit span Verbal fluency test Boston naming test Trial making, part A (sec) Apo ε2/ε3/ε4 genotypes ε2ε2/ε2ε3/ε3ε3 (%) ε2ε4/ε3ε4 (%) ε4ε4 (%)
75.4 6 9.8 257 (64.1%) 11.1 6 4.9 28.0 6 2.1 —
74.2 6 8.3 82 (52.2%)*o 10.2 6 4.7 26.0 6 2.8** 4.5 6 2.9**
79.1 6 8.2** 411 (51.5%)** 9.7 6 4.7** 18.3 6 5.9** 1.4 6 2.2**
— — — — —
10.0 6 2.5* 5.7 6 2.4* 10.2 6 3.0** 13.6 6 1.3 92.3 6 56.9
8.4 6 3.0** 3.9 6 2.1** 6.5 6 3.2** 11.4 6 3.0** 181.8 6 145.2**
— 339 (85.0%) 123 (79.4%)* 59 (14.8%) 28 (18.1%) 1 (0.3%) 4 (2.6%)
41 (5.3%) 504 (63.3%)** 269 (33.8%) 23 (2.9%)
** p< 0.001. * p < 0.01
P647
(SORL1) was recently found to be associated with late-onset Alzheimer disease (AD) in several populations. The present study aims at testing its genetic effect in the Han Chinese population in Taiwan. Methods: A total of 798 AD cases, 157 patients with mild cognitive impairment (MCI) and 401 cognitive-intact elder controls were enrolled. Eight single nucleotide polymorphisms (SNPs) of SORL1 and apolipoprotein E (APOE) e2/e3/e4 alleles were genotyped. Global cognitive performance was assessed by mini-mental state examination in all participants, while comprehensive evaluation of each cognitive domain was performed in AD and MCI patients. Haploview software was used for haplotype analysis. Results: SORL1 rs1784933 was significantly associated with AD risk and the GG genotype carried a reduced risk for AD (odds ratio (OR) ¼ 0.78, p ¼ 0.008). After adjustment for age, sex, and APOE e4 allele, rs1784933 remained to be independent predictors of AD (Adj p ¼ 0.004). The influence of SORL1 rs1784933 was also evident in MCI patients (OR ¼ 0.69, p ¼ 0.012), and remained to be significant after adjustment of other covariates (Adj p ¼ 0.013). Intriguingly, the non-synonymous SNP rs2298813 leading to amino acid substitution from Threonine to Alanine at the vacuolar protein sorting domain was significantly associated with MCI susceptibility (OR ¼ 0.49, p ¼ 0.003). Haplotype analysis did not yield more significant results. Besides, none of the cognitive tests was related to SORL1 rs1784933 genotypes. Conclusions: The present study suggested that SORL1 polymorphism could alter the risk for AD and MCI in the Han Chinese population. P2-096
SPONGING OF MIRNA-146A USING AAV-ANTIMIRNA-146A-VECTORS MEDIATES SYNAPTIC AND AMYLOIDOGENIC NEUROPATHOLOGYAND COGNITIVE DEFICITS IN A 5XFAD MURINE MODEL OF ALZHEIMER’S DISEASE
Yuhai Zhao1, Peter N. Alexandrov2, Prerna Dua3, Surjyadipta Bhattacharjee1, Christian Clement4, Frank Culicchia5, James M. Hill6, Walter J. Lukiw1, 1Louisiana State University Neuroscience Center, New Orleans, LA, USA; 2Russian Academy of Medical Sciences, Moscow, Russian Federation; 3Louisiana Technical University,
Table 2 Association between SORL1 SNPs and AD/MCI (Additive model).
SNP
Note
Allele (M/m)
rs2298813 non-syn
G/A
rs2070045 SNP19
G/T
rs1699102 SNP22
C/T
rs3824968 SNP23
A/T
rs3737529
C/T
rs2282649 SNP24
T/C
rs1010159 SNP25
C/T
rs1784933
A/G
MCI vs. Control Controls MCI AD cases OR, (MM/Mm/mm) ,% (MM/Mm/mm) ,% (MM/Mm/mm) ,% p value 291/90/91 (74.6/23.1/2.3) 144/186/64 (36.5/47.2/16.2) 330/61/1 (84.2/15.6/0.3) 155/184/56 (39.2/46.6/14.2) 239/142/20 (59.6/35.4/5.0) 148/188/56 (37.8/48.0/14.3) 155/181/55 (39.6/46.3/14.1) 178/175/47 (44.5/43.8/11.8)
134/18/2 (87.0/11.7/1.3) 54/77/25 (34.6/49.4/16.0) 129/28/0 (82.2/17.8/0.0) 61/76/19 (39.1/48.7/12.2) 103/50/4 (65.6/31.8/2.5) 59/79/18 (37.8/50.6/11.5) 62/77/18 (39.5/49.0/11.5) 86/61/10 (54.8/38.9/6.4)
597/176/12 (76.1/22.4/1.5) 302/392/99 (38.1/49.4/12.5) 666/123/7 (83.7/15.5/0.9) 313/390/88 (39.6/49.3/11.1) 508/257/33 (63.7/32.2/4.1) 305/391/93 (38.7/49.6/11.8) 315/386/89 (39.9/48.9/11.3) 408/326/63 (51.2/40.9/7.9)
OR [ 0.49, p [ 0.003 Adj: PR [ 0.49, p [ 0.003 OR ¼ 1.04, p ¼ 0.794 Adj; OR ¼ 1.02, p ¼ 0.909 OR ¼ 1.13, p ¼ 0.620 Adj; OR ¼ 1.13, p ¼ 0.633 OR ¼ 0.96, p ¼ 0.772 Adj; OR ¼ 0.95, p ¼ 0.710 OR ¼ 0.77, p ¼ 0.120 Adj; OR ¼ 0.78, p ¼ 0.140 OR ¼ 0.94, p ¼ 0.659 Adj; OR ¼ 0.92, p ¼ 0.585 OR ¼ 0.95, p ¼ 0.702 Adj; OR ¼ 0.93, p ¼ 0.598 OR [ 0.69,p [ 0.012 Adj: OR [ 0.69, p [ 0.013
M ¼ major allele, m ¼ minor allele; non-syn ¼ non-synonymous; model of inheritance: additive model; Adj p: adjustment of age. sex and ApoE4 allele.
AD vs. Control OR, p value OR ¼ 0.91, p ¼ 0.455 Adj; OR ¼ 0.82, p ¼ 0.156 OR ¼ 0.89, p ¼ 0.204 Adj; OR ¼ 0.87, p ¼ 0.149 OR ¼ 1.08, p ¼ 0.637 Adj; OR ¼ 1.06, p ¼ 0.711 OR ¼ 0.93, p ¼ 0.409 Adj; OR ¼ 0.90, p ¼ 0.300 OR ¼ 0.86, p ¼ 0.164 Adj; OR ¼ 0.82, p ¼ 0.073 OR ¼ 0.93, p ¼ 0.409 Adj; OR ¼ 0.90, p ¼ 0.297 OR ¼ 0.93, p ¼ 0.462 Adj; OR ¼ 0.91, p ¼ 0.322 OR [ 0.78, p [ 0.008 Adj: 0.75, p [ 0.004
Poster Presentations: Monday, July 25, 2016 POLYMORPHISM IN CYTOCHROME P450 GENE IS ASSOCIATED WITH ALZHEIMER’S PATHOLOGY
Andrea Lessa Benedet1, Lei Yu2, Aurelie Labbe3, Sulantha S. Mathotaarachchi4, Monica Shin4,5, Tharick A. Pascoal5, Min-Su Kang6, Thomas Beaudry7, Serge Gauthier4, David A. Bennett2, Pedro Rosa-Neto4,5,8, 1Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Montreal, QC, Canada; 2 Rush University Medical Center, Chicago, IL, USA; 3McGill University, Montreal, QC, Canada; 4McGill University Research Centre for Studies in Aging, Verdun, QC, Canada; 5Translational Neuroimaging Laboratory-McGill University, Verdun, QC, Canada; 6Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging-McGill University, Montreal, QC, Canada; 7McGill Centre for Studies in Aging, Montreal, QC, Canada; 8Douglas Hospital Research Centre, Verdun, QC, Canada. Contact e-mail: tharick.alipascoal@mail. mcgill.ca Background: The cytochromes P450 (CYP) are known for their role
in metabolizing several endogenous and exogenous substrates. In the brain, they modulate blood-flow regulation, metabolize cholesterol, and participate in neuroinflammatory processes. CYP activity is also implicated in Alzheimer’s disease (AD), particularly in amyloid-b (Ab) accumulation in CSF. We examined whether genetic polymorphisms of CYP are associated with AD pathology. Methods: [18F]florbetapir-PET imaging was employed to assess brain Ab levels in 256 subjects from a discovery cohort (ADNI: 186CN, 105 lMCI, 47AD). Linear regression models examined the association of 30 SNPs from four genes of CYP (CYP3A4, CYP2C9, CYP2C19 and CYP1A1) with global [18F]florbetapirSUVR, adjusting for age, sex, and ApoE-e4carriage status. Significant signals were interrogated at the voxel level using RMINCtool, and, separately, tested for associations with CSF Ab and Ab/p-tau ratio. Neuropathologic data from the Rush ROS and MAP cohorts were used to generalize the findings to Ab load and PHFtau tangle density by immunocytochemistry in post-mortem brains (302 CN, 180 aMCI, 259 AD). Results: The analysis of [18F]florbetapir identified an intronic variant in the CYP2C19 gene (rs4388808; P¼0.0005), in which carriers of the minor-allele (G) had lower global SUVR (Figure 1). The voxel-wise analysis showed a significant effect of the SNP in the frontal and posterior cingulate cortices, as well as in the inferior parietal cortex (Figure 2). Carriers of the minor-allele were also associated with higher
Figure 2. Voxel-wise comparison between minor allele non-carriers(-) and carriers(+) of the polymorphism rs4388808 of CYP2C19. A significant difference was observed in the frontal and posterior cingulate cortices, as well as in the inferior parietal cortex. The voxel-wise analysis was adjusted for age, gender and ApoE-e4 carriage status.
CSF Ab (P¼0.003) and higher Ab/p-tau ratio (P¼0.01). In postmortem brains, minor-allele carriers had a lower Ab load (P¼0.04), lower PHFtau tangle density (P¼0.03) as well as better episodic memory (P¼0.008). Conclusions: The rs4388808, an intronic variant of the CYP2C19 gene is implicated in Ab load, tau pathology and episodic memory, where the minor-allele protects against AD pathology.
P2-094
RELATIONSHIP BETWEEN APOLIPOPROTEIN E4 GENOTYPE AND WHOLE BODY AEROBIC CAPACITY
Jill K. Morris, Eric D. Vidoni, Heather M. Wilkins, Russell H. Swerdlow, Jeffrey M. Burns, University of Kansas Alzheimer’s Disease Center, Fairway, KS, USA. Contact e-mail: [email protected] Background: Apolipoprotein e4, the primary risk gene for sporadic
Figure 1. Comparison between non-carriers(-) and carriers(+) of the minor allele of rs4388808 (CYP2C19). A significant difference was observed in brain amyloid load (A), CSF Ab levels (B) and CSF Ab/p-tau ratio (C) using ADNI cohort. Results were generalized using post-mortem data from Rush ROS and MAP cohorts, where a concordant pattern was observed in amyloid load (D), PHF-tau tangle density (E) and episodic memory scores (F). The linear models were adjusted for age, gender and ApoE-e4 carriage status.
Alzheimer’s Disease (AD), has been demonstrated to elicit detrimental effects on cellular respiration in preclinical models. However, the relationship between whole body aerobic capacity (VO2 max) and apolipoprotein e4 genotype is unclear. We sought to examine the effect of APOE e4 genotype on aerobic capacity. Methods: We enrolled 154 elderly subjects with either no dementia (ND; n¼98) or Alzheimer’s disease (AD; n¼57) in this study. All subjects underwent genotyping for APOE e4 and cardiopulmonary exercise testing. A staff exercise physiologist led the exercise test. Following a medical screen to determine cardiac risk, a modified Cornell Bruce protocol was used during treadmill exercise. Results: Diagnosis groups did not differ in age. As expected, a higher frequency of APOE e4 carriers was observed in the AD group (31, 54%) compared to the ND group (21, 21%; p<0.001). There was a main effect of APOE e4 genotype on VO2 max (p¼0.003), with APOE e4 carriers exhibiting lower VO2 max compared to APOE e4 non-carriers. VO2max did not differ by diagnosis group, and no interaction effect was observed. Conclusions: These results
Poster Presentations: Monday, July 25, 2016
support a potential effect of apolipoprotein e4 on whole body aerobic capacity in human subjects and warrant further research into potential mechanisms.
P2-095
SORL1 IS GENETICALLY ASSOCIATED WITH ALZHEIMER’S DISEASE IN HAN CHINESE
Jong-Ling Fuh1,2, Yi-Chu Liao1,2, Wei-Ju Lee2,3, Yen-Feng Wang1,2, ShihPin Chen1,2, Shuu-Jiun Wang1,2, 1Taipei Veterans General Hospital, Taipei, Taiwan; 2National Yang-Ming University Schools of Medicine, Taipei, Taiwan; 3Taichung Veterans General Hospital, Taichung, Taiwan. Contact e-mail: [email protected] Background: The recycling of the amyloid precursor protein via the
endocytic pathway plays an important role in regulating the generation of amyloid b. The neuronal sortilin-related receptor gene Table 1 Demographic data N (%) or mean 6 SD
Controls (N ¼ 401)
MCI cases (N ¼ 157)
AD cases (N ¼ 798)
Age (y) Male (%) Education (y) MMSE score 12-item word recall test Forward digit span Backward digit span Verbal fluency test Boston naming test Trial making, part A (sec) Apo ε2/ε3/ε4 genotypes ε2ε2/ε2ε3/ε3ε3 (%) ε2ε4/ε3ε4 (%) ε4ε4 (%)
75.4 6 9.8 257 (64.1%) 11.1 6 4.9 28.0 6 2.1 —
74.2 6 8.3 82 (52.2%)*o 10.2 6 4.7 26.0 6 2.8** 4.5 6 2.9**
79.1 6 8.2** 411 (51.5%)** 9.7 6 4.7** 18.3 6 5.9** 1.4 6 2.2**
— — — — —
10.0 6 2.5* 5.7 6 2.4* 10.2 6 3.0** 13.6 6 1.3 92.3 6 56.9
8.4 6 3.0** 3.9 6 2.1** 6.5 6 3.2** 11.4 6 3.0** 181.8 6 145.2**
— 339 (85.0%) 123 (79.4%)* 59 (14.8%) 28 (18.1%) 1 (0.3%) 4 (2.6%)
41 (5.3%) 504 (63.3%)** 269 (33.8%) 23 (2.9%)
** p< 0.001. * p < 0.01
P647
(SORL1) was recently found to be associated with late-onset Alzheimer disease (AD) in several populations. The present study aims at testing its genetic effect in the Han Chinese population in Taiwan. Methods: A total of 798 AD cases, 157 patients with mild cognitive impairment (MCI) and 401 cognitive-intact elder controls were enrolled. Eight single nucleotide polymorphisms (SNPs) of SORL1 and apolipoprotein E (APOE) e2/e3/e4 alleles were genotyped. Global cognitive performance was assessed by mini-mental state examination in all participants, while comprehensive evaluation of each cognitive domain was performed in AD and MCI patients. Haploview software was used for haplotype analysis. Results: SORL1 rs1784933 was significantly associated with AD risk and the GG genotype carried a reduced risk for AD (odds ratio (OR) ¼ 0.78, p ¼ 0.008). After adjustment for age, sex, and APOE e4 allele, rs1784933 remained to be independent predictors of AD (Adj p ¼ 0.004). The influence of SORL1 rs1784933 was also evident in MCI patients (OR ¼ 0.69, p ¼ 0.012), and remained to be significant after adjustment of other covariates (Adj p ¼ 0.013). Intriguingly, the non-synonymous SNP rs2298813 leading to amino acid substitution from Threonine to Alanine at the vacuolar protein sorting domain was significantly associated with MCI susceptibility (OR ¼ 0.49, p ¼ 0.003). Haplotype analysis did not yield more significant results. Besides, none of the cognitive tests was related to SORL1 rs1784933 genotypes. Conclusions: The present study suggested that SORL1 polymorphism could alter the risk for AD and MCI in the Han Chinese population. P2-096
SPONGING OF MIRNA-146A USING AAV-ANTIMIRNA-146A-VECTORS MEDIATES SYNAPTIC AND AMYLOIDOGENIC NEUROPATHOLOGYAND COGNITIVE DEFICITS IN A 5XFAD MURINE MODEL OF ALZHEIMER’S DISEASE
Yuhai Zhao1, Peter N. Alexandrov2, Prerna Dua3, Surjyadipta Bhattacharjee1, Christian Clement4, Frank Culicchia5, James M. Hill6, Walter J. Lukiw1, 1Louisiana State University Neuroscience Center, New Orleans, LA, USA; 2Russian Academy of Medical Sciences, Moscow, Russian Federation; 3Louisiana Technical University,
Table 2 Association between SORL1 SNPs and AD/MCI (Additive model).
SNP
Note
Allele (M/m)
rs2298813 non-syn
G/A
rs2070045 SNP19
G/T
rs1699102 SNP22
C/T
rs3824968 SNP23
A/T
rs3737529
C/T
rs2282649 SNP24
T/C
rs1010159 SNP25
C/T
rs1784933
A/G
MCI vs. Control Controls MCI AD cases OR, (MM/Mm/mm) ,% (MM/Mm/mm) ,% (MM/Mm/mm) ,% p value 291/90/91 (74.6/23.1/2.3) 144/186/64 (36.5/47.2/16.2) 330/61/1 (84.2/15.6/0.3) 155/184/56 (39.2/46.6/14.2) 239/142/20 (59.6/35.4/5.0) 148/188/56 (37.8/48.0/14.3) 155/181/55 (39.6/46.3/14.1) 178/175/47 (44.5/43.8/11.8)
134/18/2 (87.0/11.7/1.3) 54/77/25 (34.6/49.4/16.0) 129/28/0 (82.2/17.8/0.0) 61/76/19 (39.1/48.7/12.2) 103/50/4 (65.6/31.8/2.5) 59/79/18 (37.8/50.6/11.5) 62/77/18 (39.5/49.0/11.5) 86/61/10 (54.8/38.9/6.4)
597/176/12 (76.1/22.4/1.5) 302/392/99 (38.1/49.4/12.5) 666/123/7 (83.7/15.5/0.9) 313/390/88 (39.6/49.3/11.1) 508/257/33 (63.7/32.2/4.1) 305/391/93 (38.7/49.6/11.8) 315/386/89 (39.9/48.9/11.3) 408/326/63 (51.2/40.9/7.9)
OR [ 0.49, p [ 0.003 Adj: PR [ 0.49, p [ 0.003 OR ¼ 1.04, p ¼ 0.794 Adj; OR ¼ 1.02, p ¼ 0.909 OR ¼ 1.13, p ¼ 0.620 Adj; OR ¼ 1.13, p ¼ 0.633 OR ¼ 0.96, p ¼ 0.772 Adj; OR ¼ 0.95, p ¼ 0.710 OR ¼ 0.77, p ¼ 0.120 Adj; OR ¼ 0.78, p ¼ 0.140 OR ¼ 0.94, p ¼ 0.659 Adj; OR ¼ 0.92, p ¼ 0.585 OR ¼ 0.95, p ¼ 0.702 Adj; OR ¼ 0.93, p ¼ 0.598 OR [ 0.69,p [ 0.012 Adj: OR [ 0.69, p [ 0.013
M ¼ major allele, m ¼ minor allele; non-syn ¼ non-synonymous; model of inheritance: additive model; Adj p: adjustment of age. sex and ApoE4 allele.
AD vs. Control OR, p value OR ¼ 0.91, p ¼ 0.455 Adj; OR ¼ 0.82, p ¼ 0.156 OR ¼ 0.89, p ¼ 0.204 Adj; OR ¼ 0.87, p ¼ 0.149 OR ¼ 1.08, p ¼ 0.637 Adj; OR ¼ 1.06, p ¼ 0.711 OR ¼ 0.93, p ¼ 0.409 Adj; OR ¼ 0.90, p ¼ 0.300 OR ¼ 0.86, p ¼ 0.164 Adj; OR ¼ 0.82, p ¼ 0.073 OR ¼ 0.93, p ¼ 0.409 Adj; OR ¼ 0.90, p ¼ 0.297 OR ¼ 0.93, p ¼ 0.462 Adj; OR ¼ 0.91, p ¼ 0.322 OR [ 0.78, p [ 0.008 Adj: 0.75, p [ 0.004