Metallomic analysis of brain tissues distinguishes between cases of dementia with Lewy bodies, Alzheimer's disease, and Parkinson's disease dementia.

Background: Dementia with Lewy bodies (DLB) can be difficult to distinguish from Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) at different stages of its progression due to some overlaps in the clinical and neuropathological presentation of these conditions compared with DLB. Metallomic changes have already been observed in the AD and PDD brain-including widespread decreases in Cu levels and more localised alterations in Na, K, Mn, Fe, Zn, and Se. This study aimed to determine whether these metallomic changes appear in the DLB brain, and how the metallomic profile of the DLB brain appears in comparison to the AD and PDD brain.

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

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.

Human dementia with Lewy bodies brain shows widespread urea elevations.

Introduction: Several recent studies have uncovered the presence of widespread urea elevations in multiple neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease dementia (PDD), vascular dementia (VaD), and Huntington's disease (HD). However, it is currently unknown whether dementia with Lewy bodies also shows these alterations in urea. This study aimed to investigate if and where urea is perturbed in the DLB brain.

Widespread selenium deficiency in the brain of cases with Huntington's disease presents a new potential therapeutic target.

Background: Huntington or Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterised by both progressive motor and cognitive dysfunction; its pathogenic mechanisms remain poorly understood and no treatment can currently slow, stop, or reverse its progression. There is some evidence of metallomic dysfunction in limited regions of the HD brain; we hypothesised that these alterations are more widespread than the current literature suggests and may contribute to pathogenesis in HD.

Methods: We measured the concentrations of eight essential metals (sodium, potassium, magnesium, calcium, iron, zinc, copper, and manganese) and the metalloid selenium across 11 brain regions in nine genetically confirmed, clinically manifest cases of HD and nine controls using inductively-coupled plasma mass spectrometry.

Extensive multiregional urea elevations in a case-control study of vascular dementia point toward a novel shared mechanism of disease amongst the age-related dementias.

Introduction: Vascular dementia (VaD) is one of the most common causes of dementia among the elderly. Despite this, the molecular basis of VaD remains poorly characterized when compared to other age-related dementias. Pervasive cerebral elevations of urea have recently been reported in several dementias; however, a similar analysis was not yet available for VaD.

Multi-regional alterations in glucose and purine metabolic pathways in the Parkinson's disease dementia brain.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases, most commonly characterised by motor dysfunction, but also with a high prevalence of cognitive decline in the decades following diagnosis-a condition known as Parkinson's disease dementia (PDD). Although several metabolic disruptions have been identified in PD, there has yet to be a multi-regional analysis of multiple metabolites conducted in PDD brains. This discovery study attempts to address this gap in knowledge.

Contrasting Sodium and Potassium Perturbations in the Hippocampus Indicate Potential Na/K-ATPase Dysfunction in Vascular Dementia.

Vascular dementia (VaD) is thought to be the second most common cause of age-related dementia amongst the elderly. However, at present, there are no available disease-modifying therapies for VaD, probably due to insufficient understanding about the molecular basis of the disease. While the notion of metal dyshomeostasis in various age-related dementias has gained considerable attention in recent years, there remains little comparable investigation in VaD.

Severe and Regionally Widespread Increases in Tissue Urea in the Human Brain Represent a Novel Finding of Pathogenic Potential in Parkinson's Disease Dementia.

Widespread elevations in brain urea have, in recent years, been reported in certain types of age-related dementia, notably Alzheimer's disease (AD) and Huntington's disease (HD). Urea increases in these diseases are substantive, and approximate in magnitude to levels present in uraemic encephalopathy. In AD and HD, elevated urea levels are widespread, and not only in regions heavily affected by neurodegeneration.

Substantively Lowered Levels of Pantothenic Acid (Vitamin B5) in Several Regions of the Human Brain in Parkinson's Disease Dementia.

Pantothenic acid (vitamin B5) is an essential trace nutrient required for the synthesis of coenzyme A (CoA). It has previously been shown that pantothenic acid is significantly decreased in multiple brain regions in both Alzheimer's disease (ADD) and Huntington's disease (HD). The current investigation aimed to determine whether similar changes are also present in cases of Parkinson's disease dementia (PDD), another age-related neurodegenerative condition, and whether such perturbations might occur in similar regions in these apparently different diseases.

Widespread Decreases in Cerebral Copper Are Common to Parkinson's Disease Dementia and Alzheimer's Disease Dementia.

Several studies of Parkinson's disease (PD) have reported dysregulation of cerebral metals, particularly decreases in copper and increases in iron in substantia nigra (SN). However, few studies have investigated regions outside the SN, fewer have measured levels of multiple metals across different regions within the same brains, and there are no currently-available reports of metal levels in Parkinson's disease dementia (PDD). This study aimed to compare concentrations of nine essential metals across nine different brain regions in cases of PDD and controls.

Effects of Alterations of Post-Mortem Delay and Other Tissue-Collection Variables on Metabolite Levels in Human and Rat Brain.

The use of post-mortem human tissue is indispensable in studies investigating alterations in metabolite levels in neurodegenerative conditions such as Alzheimer's disease (AD). However, variability between samples may have unknown effects on metabolite concentrations. The aim of this study was to characterize the impact of such variables.

Shared perturbations in the metallome and metabolome of Alzheimer's, Parkinson's, Huntington's, and dementia with Lewy bodies: A systematic review.

Despite differences in presentation, age-related dementing diseases such as Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HD), and dementia with Lewy bodies (DLB) may share pathogenic processes. This review aims to systematically assemble and compare findings in various biochemical pathways across these four dementias. PubMed and Google Scholar were screened for articles reporting on brain and biofluid measurements of metals and/or metabolites in AD, PD, HD, or DLB.

Evidence that levels of nine essential metals in post-mortem human-Alzheimer's-brain and ex vivo rat-brain tissues are unaffected by differences in post-mortem delay, age, disease staging, and brain bank location.

Studies of neurodegenerative conditions such as Alzheimer's disease (AD) using post mortem brain tissues have uncovered several perturbations in metals such as copper, iron, and zinc. However, studies of the effects of key, potentially confounding variables on these tissues are currently lacking. Moreover, human-brain tissues have limited availability, further enhancing the difficulty of matching potentially-significant variables including age, sex-matching, post-mortem delay (PMD), and neuropathological stage.

Vitamin B5 (d-pantothenic acid) localizes in myelinated structures of the rat brain: Potential role for cerebral vitamin B5 stores in local myelin homeostasis.

Vitamin B5 (d-pantothenic acid; pantothenate) is an essential trace nutrient that functions as the obligate precursor of coenzyme A (CoA), through which it plays key roles in myriad biological processes, including many that regulate carbohydrate, lipid, protein, and nucleic acid metabolism. In the brain, acetyl-CoA is necessary for synthesis of the complex fatty-acyl chains of myelin, and of the neurotransmitter acetylcholine. We recently found that cerebral pantothenate is markedly lowered, averaging ∼55% of control values in cases of Huntington's disease (HD) including those who are pre-symptomatic, and that regions where pantothenate is lowered correspond to those which are more severely damaged.