Alzheimer’s, Cognitive Impairment Linked With Choroid Plexus Volume

Increased volume of the choroid plexus, which produces and secretes cerebrospinal fluid (CSF), was tied to cognitive impairment and Alzheimer’s disease, a retrospective study showed.

Among 532 adults with cognitive symptoms, choroid plexus volume was greater in patients at more severe stages of cognitive impairment, reported Won-Jin Moon, MD, PhD, of Konkuk University School of Medicine in Seoul, Korea, and co-authors.

Ratios of intracranial volume × 10³ were 0.9 in people with subjective cognitive impairment, 1.0 in those with early mild cognitive impairment, 1.1 in late mild cognitive impairment, and 1.3 in Alzheimer’s disease (P<0.001), Moon and colleagues wrote in Radiology.

“Researchers believe impaired clearance rather than overproduction of abnormal amyloid and tau is responsible for Alzheimer’s disease,” Moon said in a statement. “Thus, we assume that the abnormal status of choroid plexus is linked to the failure of clearance leading to waste and toxic protein accumulation in the brain and failure of immune surveillance leading to neuroinflammation.”

“We found no relationship between choroid plexus volume and amyloid pathology but a clear relationship between the choroid plexus volume and cognitive impairment severity,” she added.

Breakdown of the blood-brain barrier has received much attention in Alzheimer’s and other neurologic disorders, but breakdown of the blood-CSF barrier is a newer concept, noted Gloria Chiang, MD, of Weill Cornell Medical College in New York City, in an accompanying editorial.

“CSF is produced and secreted by the choroid plexus, which consists of a single layer of ciliated epithelial cells, fluid-filled connective tissue, and fenestrated blood vessels located in the lateral, third, and fourth ventricles,” Chiang wrote. “The fenestrated vessels allow for high permeability, enabling choroid plexus epithelial cells to produce CSF from the blood.”

“However, tight junctions line the apical surface of the epithelial cells, preventing potentially toxic blood-borne substances from leaking easily into the ventricular system, thereby forming the blood-CSF barrier,” she added.

Besides producing CSF, the choroid plexus may have a more direct role in clearing amyloid, Chiang pointed out.

“The transporters, lipoprotein receptor-related proteins 1 and 2, are located on the choroid plexus epithelium and are involved in amyloid-beta clearance,” she wrote. “The blood-CSF barrier also secretes the protein transthyretin, which can bind soluble amyloid-beta to facilitate clearance. Indeed, transplanting choroid plexus cells into a mouse model of Alzheimer’s disease was found to decrease amyloid-beta deposition and improve cognition.”

Moon and colleagues assessed 532 cognitively impaired patients who had 3.0-Tesla MRI brain scans between January 2013 and May 2020. Mean age was 72 and 73% were women. Overall, 78 people had subjective cognitive impairment, 158 were diagnosed clinically with early mild cognitive impairment, 149 with late mild cognitive impairment, and 147 with Alzheimer’s disease.

About 18% of patients had amyloid PET scans; these showed that amyloid deposition was not tied to choroid plexus volume (P=0.98). Choroid plexus volume was linked with age (P<0.001), male sex (P<0.001), and hypertension (P=0.01).

Higher choroid plexus volume was negatively associated with memory (B -0.67, P=0.01), executive function (B -0.90, P=0.01), and Mini-Mental State Examination z-scores (B -0.82, P=0.01).

Of the 532 participants, 132 underwent permeability imaging using dynamic contrast-enhanced MRI. Choroid plexus permeability was reduced in patients with Alzheimer’s disease, compared with people not diagnosed with Alzheimer’s.

The results may point to a new role for MRI in Alzheimer’s diagnosis, Moon noted.

“I think our findings on the choroid plexus can suggest it as a new potential MR imaging surrogate for an impaired clearance system and neuroinflammation,” she said. “If we combine choroid plexus volume and hippocampal volume in a screening stage, it may help us better discriminate the more vulnerable patients from the less vulnerable ones.”

The study had several limitations: it was cross-sectional and temporal relationships could not be evaluated. Fewer than 20% of patients had amyloid PET imaging. Patients met clinical criteria for mild cognitive impairment and Alzheimer’s disease, but some may not have had amyloid deposition.

The researchers are planning a longitudinal study to assess choroid plexus volume changes over time as Alzheimer’s disease progresses.