USC Study Discovers Potential Early Sign of Alzheimer’s Disease

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by Kara Elam |

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A research article, titled, “Blood-Brain Barrier Breakdown in the Aging Human Hippocampus” published in the journal Neuron by a team of investigators from the Zilkha Neurogenetic Institute (ZNI) at the University of Southern California (USC) Keck School of Medicine used high-resolution MRI analysis to evaluate the regional permeability of the blood brain barrier (BBB) in the living human brain. The study looked at the age dependent breakdown in regions of the brain that are considered critical for both learning and memory, and are also shown to be affected early in patients diagnosed with Alzheimer’s disease (AD).

AD is a neurological disease that causes patients to have debilitating declines in brain function. It affects a patient’s memory, thinking, and cognitive reasoning skills. According to the CDC, as many as 5 million Americans are suffering from AD. The symptoms of the disease often first appear after age 60, and the risk for diagnosis increases substantially with age. It is projected that by 2050 the number of diagnosed cases will be in the range of 14 million.

The research team examined brain images from 64 human subjects of various ages, and found that early vascular leakage in the normally aging human brain occurs in the hippocampus, which usually shows the highest BBB properties compared to other brain regions. The BBB also showed more damage in the hippocampal area among people with dementia than those without dementia. They also analyzed the subjects’ cerebral spinal fluid (CSF) and found that individuals with dementia also showed a 115 percent increase of a protein that is indicative of pericyte injury. Pericytes are cells that surround blood vessels and help maintain the blood brain barrier; previous research has linked pericytes to dementia and aging.  The conclusions suggest that BBB breakdown is an early event in the aging human brain that begins in the hippocampus and may contribute to the cognitive impairment seen in AD.

“This is a significant step in understanding how the vascular system affects the health of our brains,” said Berislav V. Zlokovic, M.D., Ph.D., director of the ZNI, the Mary Hayley and Selim Zilkha Chair for Alzheimer’s Disease Research and the study’s principal investigator. “To prevent dementias including Alzheimer’s, we may need to come up with ways to reseal the blood-brain barrier and prevent the brain from being flooded with toxic chemicals in the blood. Pericytes are the gate-keepers of the blood-brain barrier and may be an important target for prevention of dementia.”

The results of this study could have far reaching implications for AD researchers, as well as, current and future patients.