Standardized protocol captures changes in brain structure of patients with Alzheimer's disease

New data suggest the successful development of a reliable, universal, standardized protocol that captures the changes that occur in the structure of the brain known as the hippocampus.

“Alzheimer’s disease is the result of the deposit and toxic effects of two proteins — tau and amyloid beta — when these two proteins become toxic, they affect our brain cells which become dysfunctional and then eventually die,” Liana Apostolova, MD, director of the neuroimaging laboratory at the Mary S. Easton Center for Alzheimer’s Disease Research at UCLA, said during an interview with Healio.com/Psychiatry. “We have now validated a standardized protocol that is expected to be the uniform standardized technique to be used worldwide and most importantly, in clinical trials where results from clinical trials will be easily compared.”

In a study published in the journal Alzheimer’s and Dementia, Apostolova and colleagues at UCLA developed and validated the first standardized protocol that successfully measures the hippocampus. The researchers conducted the final portion of the project that validated the protocol.

Apostolova and colleagues sought to assess the pathologic validation of European Alzheimer’s Disease Consortium Alzheimer’s Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP).

“Researchers around the world have tried to develop a reliable protocol to be able to capture the changes that occur in the structure of the brain called the hippocampus. The hippocampus is a very small structure, probably the size of one’s thumb, but with the critical function of being the most important structure for recording memory,” she said. “Any information that comes in is processed by the hippocampus and then is placed in storage. The information then has to be recalled from storage and the hippocampus has the major role to make this happen.”

According to Apostolova, the hippocampus is badly affected by Alzheimer’s disease, even before the first symptoms manifest, memory loss.

The researchers used a 7 Tesla MRI scanner to examine temporal lobes of nine patients with Alzheimer’s disease and seven cognitively normal patients post-mortem. They used HarP to collect hippocampal volumes and six-micrometer-thick hippocampal slices were stained for amyloid beta, tau and cresyl violet.

What they found were significant correlations between hippocampal volume and Braak and Braak staging (P = .001), tau (P = .034), amyloid beta burden (P = .012) and neuronal count (P < .001).

“We were able to show that the hippocampal volume measured according to the standardized protocol correlates strongly with disease pathology,” Apostolova said. “It is an important step to validate pathologically because you may be able to measure anything in the brain, but if it does not correlate with disease presence in the brain, it is meaningless. It is also hoped that this methodology will be implemented into automated software so that we will be able to do this on the single-patient level and provide diagnostic information to physicians.” – by Jennifer Southall

References:

Apostolova LG, et al. Alzheimers Dem. 2015;doi:10.1016/j.jalz.2015.01.001.

For more information:

Liana Apostolova, MD, can be reached at Mary S. Easton Center for Alzheimer's Disease, Research at UCLA, 10911 Weyburn Avenue, Suite 200, Los Angeles, CA 90095-7226; email: lapostolova@mednet.ucla.edu.

Disclosures: The researchers report no relevant financial disclosures.