Genetic variant protects brain from age-related memory decline

A particular genetic allele is now deemed a protector of memory in the aging brain as demonstrated by combined genetic testing and functional MRI, according to a study published May 1 in Biological Psychology.

A protein known as KIBRA has been singled out as essential to memory and WWC1 is the gene that produces it. Study researchers included senior author Venkata S. Mattay, MD, from the programs for Clinical brain Disorders Branch; Genes Cognition and Psychosis; and Intramural Research for the National Institute of Mental Health in Bethesda, Md., as well as the Lieber Institute for Brain Development at Johns Hopkins University Medical Campus in Baltimore, and colleagues.

“Episodic memory (EM) declines with age and the rate of decline is variable across individuals,” explained Mattay et al. "A single nucleotide polymorphism (rs17070145) in the WWC1 gene that encodes the KIBRA protein critical for long-term potentiation and memory consolidation has previously been associated with EM performance, as well as differences in hippocampal engagement during EM tasks using functional magnetic resonance imaging (fMRI). In the current study, we explore the effect of this polymorphism on EM-related activity and cognitive performance across the adult life span using fMRI."

The researchers noted three forms of the WWC1 variant, named CC, TT, or CT. Each was evaluated in this study of 233 healthy subjects, aged 18-89. All participants underwent various tests gauging cognition as well as genetic phenotyping and fMRI while performing a memory task.

Results showed that the T-allele in CT and TT was attributed to better memory performance and more activity in the hippocampus, which is associated with memory processing. Not so for the remaining allele.

“Our results show a dynamic relationship between this gene and increasing age on hippocampal function and episodic memory with the non-T allele group showing a significant decline across the adult life span,” Mattay said in a press release about the study. “A similar relationship was not observed in the T-allele carrying group suggesting that this variant of the gene may confer a protective effect.”

These biomarkers, protective and otherwise, could one day lead to targeted treatments to improve memory in patients suffering from memory decline brought on by age.