Researchers detail blood-brain barrier changes linked to Alzheimer’s disease

Summary: In people with Alzheimer’s disease, the choroid plexus enlarges and shows an increased accumulation of abnormal inflammatory signatures.

Source: Gen

A grape-shaped structure in the brain called the choroid plexus enlarges and shows increased accumulation of abnormal inflammatory molecular signals in people with Alzheimer’s disease, according to a new study published in the journal Alzheimer’s and dementia.

An international team of researchers, including scientists from the Translational Genomics Research Institute (TGen), part of City of Hope, show that these changes appear to be a more extreme or disrupted version of changes seen in the choroid plexus, part of the blood . brain barrier – during normal aging.

The choroid plexus increases in volume with age and Alzheimer’s disease. A striking finding from the study was that “the larger the choroid plexus, the lower the cognitive performance in these Alzheimer’s disease patients,” said Gorazd B. Stokin, MD, Ph.D., researcher Principal at the International Center for Clinical Research at St. Ann’s University Hospital Brno, Czech Republic, and senior author of the study.

The choroid plexus is a network of blood vessels and cells that produces cerebrospinal fluid (CSF) and creates a barrier between the CSF and blood circulating throughout the body. Through the production of CSF, the choroid plexus helps maintain the activation of the brain’s immune system.

The scientists compared the CSF choroid plexus in healthy individuals and people with Alzheimer’s disease, as well as in patients with other neurological diseases such as acute Lyme disease and amyotrophic lateral sclerosis or ALS. They analyzed inflammatory signaling in the CSF, as well as changes in structure and volume of the choroid plexus in postmortem brains and in patients using MRI.

Following studies that show that the choroid plexus can be damaged in aging and Alzheimer’s disease, Dr. Stokin and his colleagues wanted to focus more deeply on the role this tissue may play in the disease’s neuroinflammation.

The researchers found protein abnormalities and “aberrant signaling of immune molecules” in the CSF and choroid plexus of people with Alzheimer’s disease,” said study author Patrick Pirrotte, Ph.D. , director of the TGen Collaborative Center for Translational Mass Spectrometry.

Although these biological changes are also found in normal aging, he noted, they are different from those seen in other neurological disorders examined in the study.

The changes seen in aging and Alzheimer’s disease patients were most pronounced in the 66 to 75 age group, the researchers found.

This shows the outline of a head
The choroid plexus increases in volume with age and Alzheimer’s disease. Image is in public domain

“Changes in choroid plexus volume in this group might be related to the recruitment of more inflammatory cells,” said Mária Čarná, Ph.D., of St. Ann’s University Hospital in Brno, and first author of the item. “With the help of cognitive performance tests performed by some patients, the team also showed that increased choroid plexus volume was correlated with lower cognitive performance.”

The researchers cautioned that more work needs to be done to determine whether these changes in the choroid plexus and CSF cause Alzheimer’s disease or if they reflect the disease state.

Dr. Pirrotte continues to work on potential external risk factors that could exacerbate these changes, “and could accelerate the development of Alzheimer’s disease,” he said. Last year, for example, he and his colleagues published a study on how the herbicide glyphosate can increase pro-inflammatory molecules in the brain that may be linked to neurodegeneration.

About this Alzheimer’s disease research news

Author: Ham Becky
Source: Gen
Contact: Becky Ham – TGen
Picture: Image is in public domain

Original research: Free access.
“Pathogenesis of Alzheimer’s disease: involvement of the choroid plexus” by Maria Čarna et al. Alzheimer’s and dementia

See also

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Pathogenesis of Alzheimer’s disease: Involvement of the choroid plexus

The choroid plexus (ChP) produces and bathes in cerebrospinal fluid (CSF), which in aging and Alzheimer’s disease (AD) shows extensive proteomic alterations, including signs of inflammation.

Considering that inflammation impairs the functions of involved tissues, CSF abnormalities reported in these conditions suggest ChP injury. Indeed, several studies document the damage of ChP in aging and AD, which nevertheless remain to be systematically characterized.

Here we report that AD-induced changes in CSF are consistent with a disrupted aging process and accompanied by an aberrant accumulation of inflammatory signals and metabolically active proteins in ChP.

Magnetic resonance imaging (MRI) shows that these molecular aberrations correspond to significant ChP remodeling in AD, which correlates with aging and cognitive decline.

Collectively, our foreplay autopsy and in vivo findings reveal a repertoire of ChP pathologies indicating its dysfunction and involvement in AD pathogenesis.

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