Genes to remember : imaging genetics of hippocampus-based memory functions

Sammanfattning: In the field of imaging genetics, brain function and structure are used as intermediate phenotypes between genes and cognition/diseases to validate and extend findings from behavioral genetics. In this thesis, three of the strongest candidate genes for episodic memory, KIBRA, BDNF, and APOE, were examined in relation to memory performance and hippocampal/parahippocampal fMRI blood-oxygen level-dependent (BOLD) signal. A common T allele in the KIBRA gene was previously associated with superior memory, and increased hippocampal activation was observed in noncarriers of the T allele which was interpreted as reflecting compensatory recruitment. The results from the first study revealed that both memory performance and hippocampal activation at retrieval was higher in T allele carriers (study I). The BDNF 66Met and APOE ε4 alleles have previously been associated with poorer memory performance, but their relation to brain activation has been inconsistent with reports of both increased and decreased regional brain activation relative to noncarriers. Here, decreased hippocampal/parahippocampal activation was observed in carriers of BDNF 66Met (study II) as well as APOE ε4 (study III) during memory encoding. In addition, there was an additive gene-gene effect of APOE and BDNF on hippocampal and parahippocampal activation (study III). Collectively, the results from these studies on KIBRA, BDNF, and APOE converge on higher medial temporal lobe activation for carriers of a high-memory associated allele, relative to carriers of a low-memory associated allele. In addition, the observed additive effect of APOE and BDNF demonstrate that a larger amount of variance in BOLD signal change can be explained by considering the combined effect of more than one genetic polymorphism. These imaging genetics findings support and extend previous knowledge from behavioral genetics on the role of these memory-related genes.