While the cognitive and behavioral impacts of Alzheimer's can be clearly witnessed in patients, the disease's cellular function and methods for disrupting thought and memory have not been well understood. By conducting this research, NSI scientists and their collaborators have demonstrated how proteins involved in brain cell communications, called synaptic proteins, decrease in the brains of Alzheimer's patients when compared to healthy brains from people in the same age range.
"More importantly, we found that the decrease of synaptic protein levels in the frontal cortex of the brains of Alzheimer's patients was more severe than in other portions of the brain," explained P. Hemachandra Reddy, Ph.D., scientist at the Neurological Sciences Institute and first and corresponding author of the paper. "Because the frontal cortex is home to important brain functions such as reasoning, planning, and abstract thought - all affected by Alzheimer's - this finding appears to be significant. Furthermore, we noticed that synaptic protein levels were even lower in the brains of patients in the early stages of Alzheimer's disease. This suggests to us that the loss of these important proteins happens very early in the disease process."
One possible reason for the reduction of synaptic proteins is mitochondrial dysfunction, a well-documented occurrence in Alzheimer's. The researchers believe it's possible that defective mitochondria in Alzheimer's neurons may not move effectively and may not supply adequate levels of Adenosine Triphosphate (ATP). ATP is an important cellular chemical that bonds at nerve terminals for normal neural communication. The low levels of cellular ATP at nerve terminals may lead to the loss of synapses and synaptic function, and may ultimately cause cognitive decline in AD patients.
To conduct this research, Reddy and his colleagues studied 36 brain specimens from both deceased Alzheimer's patients and deceased non-Alzheimer's adults. The scientists specifically measured proteins that take part in cellular communication. Cells communicate through connections called synapses. Tiny electrical impulses pass from cell to cell at these synapses. The process also involves a variety of proteins that play various roles prior to, and following these cell transmissions. These proteins are referred to as presynaptic and postsynaptic proteins respectively. Of the seven proteins being studied, data analysis revealed that the presynaptic proteins called synaptophysin and rab 3a and the postsynaptic protein called synaptopodin decreased the most in the brains of Alzheimer's patients.
"What this study helps demonstrate is that the decrease of synaptic proteins is an early and important impact of Alzheimer's disease that likely impacts one of the brains most important functions - communication," added Reddy. ""Moreover we now know much more about where these changes are taking place and what appear to be the proteins most severely impacted to the disease."
Collaborators on this research project include the Harvard Tissue Resource Center and the Oregon Brain Bank. This research was funded by the Alzheimer's Association of Oregon, the Medical Research Foundation of Oregon, the American Federation for Aging Research and the Alzheimer's Disease Center of Oregon.
The other study authors are: Geethalakshmi Mani, Joline Jacques, Maria Manczak, OHSU Neurological Sciences Institute; Geoffrey Murdoch, Department of Pathology, OHSU School of Medicine; Jeffrey Kaye, Department of Neurology, OHSU School of Medicine; Byung S. Park, Division of Biostatistics, Department of Public Health and Preventive Medicine, OHSU School of Medicine; William Whetsell Jr. Department of Pathology, Vanderbilt University Medical Center, Nashville, TN.