Study Tries to Unravel Vitamin D Pathway in Brains of Patients With PD

In a study published this month, researchers said they now have clarity into the vitamin D pathway in the brains of patients with Parkinson disease.

Vitamin D is thought to have neuroprotective effects and it is usually lacking in patients with PD. The nerve cell loss in PD is thought to be triggered mainly by the toxic buildup of alpha-synuclein (α-synuclein). Astrocytes, a type of glial cell, are involved in PD in 2 ways: they both add to α-synuclein pathology but also help clear α-synuclein.

Researchers in Italy analyzed vitamin D pathway components CYP27B1, CYP24A1, and 1,25-dihydroxyvitamin D receptor (VDR) in brain tissue obtained from 9 deceased patients with PD and 4 controls without neurodegenerative disease.

Patients with PD numbered 5 men and 4 women aged 71 to 91 at time of death. All had severe α-synuclein-related neurodegeneration. The controls included 3 women and 1 man, all aged 64 to 93.

CYP27B1 astrocytes were found in the brains of PD patients but not controls.

The researchers also found that the level of CYP27B1 expression correlated with clinical aspects of disease. Expression in the frontal cortex white matter was significantly higher in patients with Lewy body pathology, but without white matter alteration or dementia, while patients with PD and white matter alterations and dementia had significantly fewer CYP27B1 positive astrocytes in the cortex, although there was no difference in the total number of filament cells related to neuronal damage.

“We found that the brains of PD patients without dementia have a threefold higher content of CYP27B1 positive astrocytes in the frontal cortex and do not have white matter degeneration, thus suggesting that vitamin D could exert its neuroprotective role through astrocytes,” the researchers wrote.

One limitation of the study is that they could not assess vitamin D levels in the deceased patients or explore their genetic status.

The researchers called the relationship between vitamin D and PD “complex” and called for further studies.

Reference

Mazzetti S, Barichella M, Giampietro F, et al. Astrocytes expressing Vitamin D-activating enzyme identify Parkinson’s disease. CNS Neurosci Ther. Published online February 15, 2022. doi.org/10.1111/cns.13801