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INFLUENCE OF SINGLE NUCLEOTIDE POLYMORPHISMS IN ALZHEIMER'S SUSCEPTIBILITY-LOCI ON COGNITIVE PHENOTYPES
S970
Abstracts
Discussion: An association between maternal age and off-
Results: Nominal association could be detected for 18
spring LTL and the interaction with BD was observed. It could be speculated that an influence of oxidative stress during first pregnancy, changes in mitochondrial DNA or even other parent-specific imprinting mechanism, such as DNA methylation, relevant to the neurodevelopment of the brain. To our knowledge, this is the first study evaluating association of maternal age and telomere length in the offspring of families with several members affected by BD. Additional studies are needed to confirm these preliminary findings.
SNPs affecting at least one phenotype. The most significant SNP rs983392 was associated with the subscale digit span. This polymorphism is in linkage disequilibrium with the membrane spanning 4-domains A6A-gene (MS4A6A), belonging to the MS4A gene family on Chromosome 11q12. This gene was associated with a smaller right middle temporal volume, which hosts the hippocampus. A decreasing hippocampus is known to be a symptom in Alzheimer's disease. Another notable finding was the association of rs6733839 with performance, verbal and general IQ. This SNP is located near the bridging integrator 1-gene (BIN1), located on chromosome 2q14.3. It is thought to be involved in synaptic vesicle endocytosis and modulation of tau pathology, one of the key symptoms of Alzheimer's dementia. Discussion: Results of this study indicate an influence of LOAD associated variations on cognitive performance in healthy controls. Both verbal and performance subtests show significant associations. These findings could help to improve the knowledge of pathophysiology and genetics of cognitive decline as observed LOAD. However, further research is needed to validate these associations and detect the functional relevance of the affected genes.
Disclosure: Nothing to disclose. http://dx.doi.org/10.1016/j.euroneuro.2017.08.335
M29. INFLUENCE OF SINGLE NUCLEOTIDE POLYMORPHISMS IN ALZHEIMER'S SUSCEPTIBILITY-LOCI ON COGNITIVE PHENOTYPES n
Lisa Endlich ,1, Bettina Konte2, Ina Giegling1, Annette Hartmann3, Dan Rujescu1 1
University of Halle Martin Luther University Halle-Wittenberg, University of Munich 3 University of Munich 2
Disclosure: Nothing to disclose. http://dx.doi.org/10.1016/j.euroneuro.2017.08.336
Background: Late Onset Alzheimer's Disease (LOAD) is a chronic and progressive neurodegenerative disorder affecting elderly people and is accompanied by severe cognitive decline. Genetics is supposed to be one of the key factors for the susceptibility to the disease. Several loci have been associated with an increased risk of developing Alzheimer's disease via Genome-Wide Association Studies (GWAS). The aim of this study was to investigate whether 33 susceptibility loci recently associated with LOAD in a large metaanalysis affect cognition in a healthy population. Methods: Therefore, 2147 unrelated healthy subjects of German descent were recruited. The Structured Clinical Interview for DSM-IV (SCID 1 and SCID 2) was conducted to exclude psychotic diseases, a family history was recorded to exclude subjects with a positive family history for psychotic disorders and the Mini Mental Status Examination (MMSE) was conducted for every subject being older than 60 years, to exclude possible cognitive impairments. Cognitive performance was assessed via the German version of the 'Wechsler Adult Intelligence Scale, Revision 1991' (WAIS-R). Genotype data was obtained using chip technology and imputation. After stringent quality controls 31 single nucleotide polymorphisms (SNPs) were analyzed. SNPs having mismatches between reported and estimated gender and callrate differences Z 0.02 between cases and controls were not considered. The analysis was calculated through an additive linear regression model.
M30. NEXT-GENERATION RNA SEQUENCING OF POSTMORTEM ANTERIOR CINGULATE AND DORSOLATERAL PREFRONTAL CORTICES TO IDENTIFY DIFFERENTIALLY EXPRESSED GENES IN PATHOLOGY-VERIFIED LEWY BODY DEMENTIA n
Anto Praveen Rajkumar Rajamani , Emily Bell, Paul Francis, Dag Aarsland King's College London
Background: Lewy Body Dementias (LBD) include Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD). DLB is the second most common neurodegenerative dementia, and it is associated with increased mortality, earlier nursing home admissions, higher risk of falls, poorer quality-of-life, more health resource utilisation, higher costs, and more caregivers’ burden than Alzheimer's disease. There are no diseasemodifying treatments for LBD, and reliable cost-effective biomarkers that can aid early diagnosis of LBD remain elusive. Identifying Differentially Expressed Genes (DEG) in LBD brains can reveal underlying functionally disrupted molecular pathways, and it may lead to novel biomarkers and potential RNA drugs for LBD.
Abstracts
Discussion: An association between maternal age and off-
Results: Nominal association could be detected for 18
spring LTL and the interaction with BD was observed. It could be speculated that an influence of oxidative stress during first pregnancy, changes in mitochondrial DNA or even other parent-specific imprinting mechanism, such as DNA methylation, relevant to the neurodevelopment of the brain. To our knowledge, this is the first study evaluating association of maternal age and telomere length in the offspring of families with several members affected by BD. Additional studies are needed to confirm these preliminary findings.
SNPs affecting at least one phenotype. The most significant SNP rs983392 was associated with the subscale digit span. This polymorphism is in linkage disequilibrium with the membrane spanning 4-domains A6A-gene (MS4A6A), belonging to the MS4A gene family on Chromosome 11q12. This gene was associated with a smaller right middle temporal volume, which hosts the hippocampus. A decreasing hippocampus is known to be a symptom in Alzheimer's disease. Another notable finding was the association of rs6733839 with performance, verbal and general IQ. This SNP is located near the bridging integrator 1-gene (BIN1), located on chromosome 2q14.3. It is thought to be involved in synaptic vesicle endocytosis and modulation of tau pathology, one of the key symptoms of Alzheimer's dementia. Discussion: Results of this study indicate an influence of LOAD associated variations on cognitive performance in healthy controls. Both verbal and performance subtests show significant associations. These findings could help to improve the knowledge of pathophysiology and genetics of cognitive decline as observed LOAD. However, further research is needed to validate these associations and detect the functional relevance of the affected genes.
Disclosure: Nothing to disclose. http://dx.doi.org/10.1016/j.euroneuro.2017.08.335
M29. INFLUENCE OF SINGLE NUCLEOTIDE POLYMORPHISMS IN ALZHEIMER'S SUSCEPTIBILITY-LOCI ON COGNITIVE PHENOTYPES n
Lisa Endlich ,1, Bettina Konte2, Ina Giegling1, Annette Hartmann3, Dan Rujescu1 1
University of Halle Martin Luther University Halle-Wittenberg, University of Munich 3 University of Munich 2
Disclosure: Nothing to disclose. http://dx.doi.org/10.1016/j.euroneuro.2017.08.336
Background: Late Onset Alzheimer's Disease (LOAD) is a chronic and progressive neurodegenerative disorder affecting elderly people and is accompanied by severe cognitive decline. Genetics is supposed to be one of the key factors for the susceptibility to the disease. Several loci have been associated with an increased risk of developing Alzheimer's disease via Genome-Wide Association Studies (GWAS). The aim of this study was to investigate whether 33 susceptibility loci recently associated with LOAD in a large metaanalysis affect cognition in a healthy population. Methods: Therefore, 2147 unrelated healthy subjects of German descent were recruited. The Structured Clinical Interview for DSM-IV (SCID 1 and SCID 2) was conducted to exclude psychotic diseases, a family history was recorded to exclude subjects with a positive family history for psychotic disorders and the Mini Mental Status Examination (MMSE) was conducted for every subject being older than 60 years, to exclude possible cognitive impairments. Cognitive performance was assessed via the German version of the 'Wechsler Adult Intelligence Scale, Revision 1991' (WAIS-R). Genotype data was obtained using chip technology and imputation. After stringent quality controls 31 single nucleotide polymorphisms (SNPs) were analyzed. SNPs having mismatches between reported and estimated gender and callrate differences Z 0.02 between cases and controls were not considered. The analysis was calculated through an additive linear regression model.
M30. NEXT-GENERATION RNA SEQUENCING OF POSTMORTEM ANTERIOR CINGULATE AND DORSOLATERAL PREFRONTAL CORTICES TO IDENTIFY DIFFERENTIALLY EXPRESSED GENES IN PATHOLOGY-VERIFIED LEWY BODY DEMENTIA n
Anto Praveen Rajkumar Rajamani , Emily Bell, Paul Francis, Dag Aarsland King's College London
Background: Lewy Body Dementias (LBD) include Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD). DLB is the second most common neurodegenerative dementia, and it is associated with increased mortality, earlier nursing home admissions, higher risk of falls, poorer quality-of-life, more health resource utilisation, higher costs, and more caregivers’ burden than Alzheimer's disease. There are no diseasemodifying treatments for LBD, and reliable cost-effective biomarkers that can aid early diagnosis of LBD remain elusive. Identifying Differentially Expressed Genes (DEG) in LBD brains can reveal underlying functionally disrupted molecular pathways, and it may lead to novel biomarkers and potential RNA drugs for LBD.