MedicalResearch.com Interview with:
Vijay Ramanan, PhD
Indiana University Center for Neuroimaging (CfN)
Department of Radiology
Indianapolis, IN 46202
Medical Research: What is the background for this study? What are the main findings?
Dr. Ramanan: Impairment in episodic memory is one of the first clinical deficits in early Alzheimer’s disease, the most common cause of dementia. Among other examples, this might be reflected as an inability to recall an article recently read or as difficulty remembering what one had for dinner last night. Unfortunately, the genetic and environmental mechanisms underlying these deficits are not fully understood. Our goal was to discover new genes and pathways underlying memory performance to help identify potential drug targets for protecting against and ultimately reversing memory loss in dementia and normal aging.
Through studying a large representative sample of older Americans, we discovered a variant (single nucleotide polymorphism or SNP) in the
FASTKD2 gene associated with better memory performance and replicated this finding in independent samples. We then integrated additional data to extend our understanding of the effect of this SNP. For example, we know that the hippocampus is a vital brain structure for encoding and retrieving memories and it is well-understood that decreased hippocampal volume is a key early marker of
Alzheimer’s disease and one that can be measured noninvasively through magnetic resonance imaging (MRI). We predicted that this new memory-protective SNP would be associated with increased hippocampal volume and this turned out to be true. We also discovered that carriers of this memory-protective SNP exhibited lower levels of proteins involved in cell death in the cerebrospinal fluid bathing the brain and spinal cord, a striking finding given that
FASTKD2 encodes a protein that appears to promote apoptosis (i.e., programmed cell death). Together, these convergent findings are consistent with a neuroprotective effect of this novel SNP discovery. More broadly, our results nominate
FASTKD2 and its functional pathways as potential targets for modulating neurodegeneration to combat memory loss in older adults.
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