Warding off the Theft of Independence and Memories by Alzheimer’s Disease

Alzheimer’s disease (AD) robs people of their memories and their independence. Determining those at greatest risk for the disease as early as possible may prove key for warding off AD for as long as possible. Although changes in the brain can show up between 4 and 17 years prior to manifestation of AD symptoms, these are only seen by using magnetic resonance imaging (MRI); not ideal for wide-spread population screening.1 What is needed is a non-invasive, readily accessible and inexpensive diagnostic test that would help clinicians manage patient health through early intervention.

As a first step towards such a diagnostic test, Steven Kiddle and his colleagues set out to identify biomarkers that associated with thought-based tests predictive of AD.2 Using relevant blood samples from the TwinsUK study, they acquired the subjects’ proteomic profiles using the SOMAscan® assay, and compared those findings with those obtained from traditional cognitive tests to see if they could identify potential AD biomarkers. The researchers also performed MRI scans to check for AD-related physical changes in the brain.

After collecting and processing data from the numerous tests, the research group analyzed the data to identify biomarker candidates. From the 1,129 proteins measured in samples from the TwinsUK group, the researchers found associations between the levels of three different proteins and brain volume changes as seen by the MRI scans. However, when the researchers compared these volume-associated proteins with measures of cognitive function, only one of them (called MAP2K4) showed an association, and only with the 10-year change in cognitive function testing. In looking at cognitive function scores only, the researchers also found an association between the 10-year change and MAPKAPK5. This protein, however, showed a nominal association with brain volume changes.

To confirm the findings, the researchers turned to a different set of samples that came from the AddNeuroMed study, again performing MRI scans and SOMAscan. From these data, the researchers did find an association between MAP2K4 plasma protein levels and brain volume. However, the smaller sample numbers requires additional studies to be done to potentially nail down a predictive biomarker for early intervention therapy in patients showing increased risk of developing AD. Though preliminary, the findings could eventually lead to making a huge difference in how long an at-risk person can live independently and still reminisce about the past.

References

1 Villemagne VL et al. (2013) Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurology 12 (pp. 357–67)

2 Kiddle SJ et al. (2015) Plasma protein biomarkers of Alzheimer’s disease endophenotypes in asymptomatic older twins: early cognitive decline and regional brain volumes. Translational Psychiatry 5(6): e584. doi: 10.1038/tp.2015.78.