Genetic Alzheimer's Disease Risk Affects the Neural Mechanisms of Pattern Separation in Hippocampal Subfields
| Autor: | Christian Montag, Hwee Ling Lee, Sichu Wu, Sonja Jung, Nikolai Axmacher, Rüdiger Stirnberg, Tony Stöcker, Xin Wang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Apolipoprotein E Pattern separation APOE genotype Genotyping Techniques 7T CA3 genetics [Alzheimer Disease] Disease Hippocampal formation metabolism [Apolipoproteins E] 0302 clinical medicine Risk Factors diagnostic imaging [Dentate Gyrus] Medicine physiopathology [Dentate Gyrus] dentate gyrus Episodic memory Brain Mapping medicine.diagnostic_test diagnosis [Alzheimer Disease] episodic memory CA3 Region Hippocampal Magnetic Resonance Imaging Healthy Volunteers Female medicine.symptom General Agricultural and Biological Sciences Adult Heterozygote Memory Episodic Biology physiopathology [Alzheimer Disease] Asymptomatic General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Young Adult Apolipoproteins E Alzheimer Disease ddc:570 Humans pattern separation Genetic Predisposition to Disease diagnostic imaging [CA3 Region Hippocampal] Alleles Recall business.industry Dentate gyrus functional connectivity hippocampal subfields 030104 developmental biology nervous system Dentate Gyrus genetics [Apolipoproteins E] business Functional magnetic resonance imaging Neuroscience 030217 neurology & neurosurgery physiopathology [CA3 Region Hippocampal] |
| Zdroj: | Current biology 30(21), 4201-4212.e3 (2020). doi:10.1016/j.cub.2020.08.042 |
| ISSN: | 1556-5068 |
| Popis: | The hippocampal subfields perform distinct operations during acquisition, differentiation and recollection of episodic memories, and deficits in pattern separation are among the first symptoms of Alzheimer’s disease (AD). We investigated how hippocampal subfields contribute to pattern separation and how this is affected by Apolipoprotein-E (APOE), the strongest AD genetic risk factor. We scanned young healthy participants at average, high, and low AD-risk during a spatial mnemonic discrimination task using ultra-high field (7T) functional magnetic resonance imaging (fMRI). Average AD-risk carriers predominantly recruited CA3 for the task, while high and low AD-risk carriers engaged CA3 and dentate gyrus (DG) to the same degree. Specifically, high AD-risk carriers showed reduced pattern separation in CA3, while low AD-risk carriers exhibited increased effects in DG and pattern separation-related CA3-DG functional connectivity. These results demonstrate that AD genetic risk alters hemodynamic responses in young asymptomatic individuals, paving way for development of biomarkers for preclinical AD. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|