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Calcium signaling central to hippocampus-related memory processes in health, disease

Data from an international multicenter study indicated the central role calcium signaling plays in hippocampus-dependent human memory processes in cognitive health and disease, which may aid understanding and potential treatment of hippocampus-dependent cognitive pathology.

“As a consequence of physiological aging processes in brain regions, such as the hippocampus and the medial temporal lobe, performance in [episodic memory] tasks declines with age. Pathological [episodic memory] impairment is a behavioral hallmark of age-related neurodegenerative conditions, such as Alzheimer’s disease,” Angela Heck, PhD, of the University of Basel, in Switzerland, and colleagues wrote.

To determine if biologically defined gene groups are enhanced in episodic memory performance across age, brain activity associated with memory encoding and Alzheimer’s disease, researchers conducted gene set enrichment analysis using data from a primary and meta-analysis conducted across 57,968 participants of a multicenter collaborative study that began in August 2008 and is ongoing. Study participants included Swiss cohorts of 3,043 healthy young adults; a German cohort of 763 geriatric participants without dementia; and 17,008 individuals with sporadic Alzheimer’s disease and 37,154 control participants from the International Genomics of Alzheimer’s Project.

Episodic memory performance was assessed across cohorts. A subgroup (n = 1,119) of the Swiss cohorts underwent functional MRI to identify gene set-dependent differences in brain activity related to episodic memory. Analyses were conducted between January 2014 and June 2015.

Researchers found significant enrichment for genes associated with the calcium signaling pathway, particularly genes related to the elevation of cytosolic calcium. This enrichment was replicated in two samples of healthy young individuals (P = .02; P = .04, respectively) and a sample of healthy elderly individuals (P = .004).

Hippocampal activation and risk for sporadic Alzheimer’s disease (P = .01) were significantly enriched for genes related to the elevation of cytosolic calcium, according to researchers.

“By showing robust and consistently significant enrichment in independent cohorts of young and elderly participants, our study identified that calcium signaling plays a central role in hippocampus-dependent human memory processes, both in cognitive health and disease and, therefore, contributes to the understanding and potential treatment of hippocampus-dependent cognitive pathology,” the researchers concluded. – by Amanda Oldt

Disclosure: The researchers report no relevant financial disclosures.