Blood-Based Biomarkers for Memory Loss
Reference: 2014-001, 2014-037, and 2014-046
Georgetown researchers have discovered several biomarkers, including but not limited to lipids, metabolites, genes, and proteins in the blood, that can predict with close to 100% accuracy if a healthy person will develop mild cognitive impairment or Alzheimer’s disease (AD). Existing preclinical biomarkers of AD are obtained either through time-consuming and expensive neuroimaging modalities or via invasive and risky lumbar punctures for cerebrospinal fluid analyses. The present invention has the potential for a powerful blood test to identify people at risk for progressive cognitive decline. Further, the novel method can potentially be used in selecting individuals for secondary prevention trials and to provide clues for targeted therapeutic interventions.
· May be a useful clinical indicator of the stage of disease
· Biomarkers can be used to differentiate AD from Frontotemporal Dementia.
· The technology can accurately identify people at risk for progressive cognitive decline and be of value in terms of having the individuals, their families, and treating physicians plan for and manage the disorder.
· The technology can potentially be used for developing treatment strategies for Alzheimer’s at an earlier stage when therapy would be more effective at slowing or preventing the onset of symptoms.
· May be used for identifying patients for secondary prevention trials.
· Can predict among cognitive normal who will progress to disease
· Minimally-invasive (as opposed to lumbar puncture)
· Low cost (low tech, as opposed to neuroimaging)
· Quick, familiar, and easily tolerated by most individuals
· These biomarkers define the asymptomatic period in patients and are critical for the successful development and application of the therapeutics. The preclinical state of the disease offers a window of opportunity for timely disease-modifying intervention.
STAGE OF DEVELOPMENT
The study included 525 healthy participants aged 70 and older who gave blood samples upon enrolling and at various points in the study. Throughout the five-year study, 74 participants met the criteria for either mild Alzheimer’s disease (AD) or a condition known as amnestic mild cognitive impairment (aMCI), in which memory loss is prominent. Of these, 46 were diagnosed upon enrollment, and 28 developed aMCI or mild AD during the study (the latter group called converters). The metabolomic/lipidomic analyses were carried out on a discovery group of 124 subjects and a researcher’s validation group of 51 subjects.
Blinded data were analyzed to determine if the subjects could be characterized into the correct diagnostic categories based solely on the biomarkers identified in the discovery phase.
2014-001 – Issued – US 10,578,629 B2; Validated EP 3060305
2014-037– Issued – US EP WO 10,718,021 B2; Issued EP 3149208; 602015074923.5
2014-046 – Issued – US EP WO 10,890,589
- “Plasma phospholipids identify antecedent memory impairment in older adults”. Nature Medicine, April 2014; 20 (4): 415-8. https://doi.org/10.1038/nm.3466
- “Plasma 24-metabolite Panel Predicts Preclinical Transition to Clinical Stages of Alzheimer’s Disease” Front. Neurol., November 2015; https://doi.org/10.3389/fneur.2015.00237
- The critical need for defining preclinical biomarkers in Alzheimer’s disease. Alzheimers Dement. 2014 Jun;10(3 Suppl):S196-212. doi: 10.1016/j.jalz.2014.04.015. PMID: 24924671.
Howard Federoff, Massimo Fiandaca, Mark Mapstone, Amrita Cheema, Yuriy Gusev, and Xiaogang Zhang