$2M NIH Grant Goes to Study of Infection’s Role in Alzheimer’s

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by Vanda Pinto |

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The National Institutes of Health (NIH) has awarded a $2-million grant to support research into the role of infections in the development of Alzheimer’s disease.

The preclinical study will be conducted at The University of Texas Health Science Center at Houston (UTHealth).

“If we can prove the theory that infection is one of the factors that triggers Alzheimer’s disease, and specifically sepsis and meningitis, we can pay more attention to these diseases and possibly be able to avoid the onset of dementia for people in the long term,” Tatiana Barichello, PhD, co-principal investigator of the study, said in a press release.

Alzheimer’s disease is a neurologic disorder and the most common cause of dementia. Several factors are thought to contribute to its development, including genetics, age, lifestyle, and certain health conditions.

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Now, researchers at UTHealth, under the supervision of Rodrigo Morales, PhD, associate professor in the department of neurology at the university’s McGovern Medical School, will study the role of sepsis and meningitis in the development of Alzheimer’s and seek to identify the underlying molecular and cellular mechanisms.

Sepsis is a widespread inflammatory reaction caused by infection, and meningitis is an infection of the membranes that protect the brain and spinal cord.

Researchers hope that doctors would, in the future, be able to identify patients who have an increased risk of developing Alzheimer’s based on whether they previously had sepsis or meningitis.

The activation of the peripheral immune system, or the immune system outside the brain and spinal cord, could be a link between infections and the development of Alzheimer’s, according to Morales. Immune responses in the brain, or in other peripheral locations, could activate resident immune cells in the brain. The team’s hypothesis is that “chronic immune activation or severe acute events may lead to different clinical conditions at short or long terms.”

“Imbalance in the immune system may also increase the production of certain proteins that may initiate Alzheimer’s disease,” Morales said.

The researchers pointed out that a damaged blood-brain barrier could be another link between infections and an increased risk of developing Alzheimer’s.

“The blood-brain barrier acts as the defense mechanism for the brain allowing certain substances to enter the brain and keeping other substances out, but during an event like an injury or infection, that barrier is compromised, which allows those substances that might be harmful to the brain to enter it,” said Morales. “These substances can lead to the buildup of inflammation in the brain, which in turn can lead to the development of Alzheimer’s disease.”

Transgenic mice and human samples will be used in the study, as well as a technology known as protein misfolding cyclic amplification. This in vitro technique has been previously shown to detect altered proteins associated with Parkinson’s and Creutzfeldt-Jakob disease.

The project was funded by the National Institute on Aging, part of the NIH.