Memory Mondays: Early Signs of Alzheimer’s at Age 40

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From behavioral changes and vision impairment to speech struggles and hearing loss, there are many early signs of Alzheimer’s. Now, scientists are pointing to brain changes that could start as early as age 40 and predict the onset of Alzheimer’s later in life.

Researchers at the University of Southern California uncovered a process that comes before the buildup of toxic proteins associated with dementia. In a study with mice, they found that damage to cells called pericytes (those that line the walls of capillaries) can trigger white matter disease, in which brain tissue with nerve fibers – or white matter – become damaged. This, in turn, causes trouble with memory, thinking and balance.

White matter disease is common in older adults, according to Berislav Zlokovic, senior study author. But the exact way in which the disease may lead to dementia had been unclear prior to the study.

A few findings of note include:

– Brains of people with Alzheimer’s disease had 50% fewer pericytes than healthy brains.

– Levels of fibrinogen (a blood-circulating protein that helps heal wounds) increased threefold in white matter regions.

– When pericyte-deficient mice were the equivalent to 40 human years, their levels of fibrinogen were about 10 times higher in the region of the brain responsible for transmitting cognitive and sensory data from one side of the brain to the other.

– At the equivalent to 70 human years, the mice displayed a 50% increase in blood vessel leakage.

“Our observations suggest that once pericytes are damaged, blood flow in the brain reduces like a drain that is slowly getting clogged,” said co-first study author Angeliki Maria Nikolakopoulou, of the Zilkha Neurogenetic Institute at the Keck School of Medicine.

As the blood flow lessens, blood vessels become damaged, white matter frays and brain connections get disrupted. This then indicates early signs of Alzheimer’s.

“Many scientists have focused their Alzheimer’s disease research on the buildup of toxic amyloid and tau proteins in the brain, but this study and others from my lab show that the problem starts earlier – with leaky blood vessels in the brain,” Zlokovic noted.

Essentially, the findings may point toward fibrinogen as a target for preventing the onset of dementia. However, further studies are necessary, according to the researchers.

“We must figure out the right approach,” Zlokovic said. “Perhaps focusing on strengthening the blood-brain barrier integrity may be an answer because you can’t eliminate fibrinogen from blood in humans. This protein is necessary in the blood. It just happens to be toxic to the brain.”