Localized Pantothenic Acid (Vitamin B5) Reductions Present Throughout the Dementia with Lewy Bodies Brain

Abstract

Background: Localized pantothenic acid deficiencies have been observed in several neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease dementia (PDD), and Huntington's disease (HD), indicating downstream energetic pathway perturbations. However, no studies have yet been performed to see whether such deficiencies occur across the dementia with Lewy bodies (DLB) brain, or what the pattern of such dysregulation may be.

Objective: Firstly, this study aimed to quantify pantothenic acid levels across ten regions of the brain in order to determine the localization of any pantothenic acid dysregulation in DLB. Secondly, the localization of pantothenic acid alterations was compared to that previously in AD, PDD, and HD brains.

Methods: Pantothenic acid levels were determined in 20 individuals with DLB and 19 controls by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) across ten brain regions. Case-control differences were determined by nonparametric Mann-Whitney U test, with the calculation of S-values, risk ratios, E-values, and effect sizes. The results were compared with those previously obtained in DLB, AD, and HD.

Results: Pantothenic acid levels were significantly decreased in six of the ten investigated brain regions: the pons, substantia nigra, motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. This level of pantothenic acid dysregulation is most similar to that of the AD brain, in which pantothenic acid is also decreased in the motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. DLB appears to differ from other neurodegenerative diseases in being the only of the four to not show pantothenic acid dysregulation in the cerebellum.

Conclusions: Pantothenic acid deficiency appears to be a shared mechanism of several neurodegenerative diseases, although differences in the localization of this dysregulation may contribute to the differing clinical pathways observed in these conditions.

Keywords: Lewy body dementia; Pantothenic acid; UHPLC–MS/MS; dementia with Lewy bodies; mass spectrometry; metabolomics; vitamin B5.

Fig. 1

Pantothenic acid concentrations in DLB cases and controls. Figure shows mean urea concentrations±95% confidence intervals in μM/Kg. Case–control differences were determined using Mann–Whitney U test. CB, Cerebellum; SN, Substantia nigra; MCX, Motor cortex; CG, Cingulate gyrus; MED, Medulla; MTG, Middle temporal gyrus; PVC, Primary visual cortex; PUT, Putamen; HP, Hippocampus.

Fig. 2

Comparison of pantothenic acid alterations in DLB, PDD, AD, and HD brains. Blue regions indicate decreases in pantothenic acid. Grey regions indicate no changes in pantothenic acid. Grey dotted shading indicates that region was not investigated in that condition. CB, Cerebellum; CG, Cingulate Gyrus; ENT, Entorhinal Cortex; HP, Hippocampus; MED, Medulla; MCX, Motor Cortex; MFG, Middle frontal gyrus; MTG, Middle Temporal Gyrus; PUT, Putamen; PVC, Primary visual cortex; SN, Substantia Nigra.