At today’s plenary session, Lipidomics: A Powerful Approach to Identify Pre-clinical Memory Impairment in Older Adults, Amrita Cheema, PhD, will share her team’s recent research published in Nature Medicine that proposes a panel of lipids to detect preclinical Alzheimer’s disease (doi:10.1038/nm.3466).
In this proof-of-concept study, led by Howard Federoff, MD, PhD, the researchers used mass spectrometry to identify a panel of lipids in blood that could predict the onset of cognitive impairment over a 2-3 year period. Their validation phase included 10 individuals that developed cognitive impairment during the course of the study, along with individuals whose cognitive status was stable over the course of the study—20 cognitively normal and 11 cognitively impaired. They found that a 10-lipid panel predicted the progression from cognitively normal to cognitively impaired in this small group with a sensitivity of 90% and a specificity of 90%.
Cheema will discuss the motivation behind the study—trying to identify individuals with preclinical, asymptomatic Alzheimer’s disease—as this phase of the disease provides potentially the greatest opportunity to slow or reverse the progression of dementia. The preclinical phase was recently identified by observing changes in cerebrospinal fluid and neuroimaging biomarkers; however, these biomarkers can’t accurately determine who is at risk for developing dementia.
While there is no cure or effective treatment for Alzheimer’s disease, there are many efforts underway that would benefit from improved prognostic and diagnostic tools. For instance, the selection of clinical trial participants would dramatically change if a biomarker panel could predict who was likely to develop dementia over the next few years. Many drug candidates for Alzheimer’s disease have failed in clinical trials. “One reason may be the drugs were evaluated too late in the disease process,” Cheema noted.
While the exact role of the lipidome in Alzheimer’s disease is ill defined, it presents an exciting area for further research. As Cheema and her colleagues have previously highlighted, there is a need for external validation of the study findings, due to their study’s proof-of-concept design. Additional studies could incorporate more diverse demographic populations; include the analysis of commonly used cerebrospinal fluid and imaging biomarkers; and use widely accepted standards for disease classifications.
Can lipidomics deliver on what earlier proteomics studies have promised: blood-based biomarkers that correlate with disease pathogenesis? Only time, and additional research, will tell.