Metallomic analysis of brain tissues distinguishes between cases of dementia with Lewy bodies, Alzheimer’s disease, and Parkinson’s disease dementia Original paper
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Parkinson’s Disease
Parkinson’s Disease
OverviewParkinson’s disease (PD) is a neurodegenerative disorder primarily characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway, leading to progressive hypokinetic movements [1], and a range of non-motor symptoms including gastrointestinal (GI) dysfunction [2]. Emerging evidence suggests that the gut microbiome may influence PD through the gut–brain axis. PD is one of the […]
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Alzheimer’s Dementia
Alzheimer’s Dementia
OverviewAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaques, neurofibrillary tangles, neuroinflammation, and metabolic dysfunction, ultimately leading to cognitive decline and dementia. Emerging research highlights the microbiota-gut-brain axis as a crucial factor in AD pathogenesis, with gut dysbiosis contributing to neuroinflammation, immune dysregulation, and blood-brain barrier permeability. Microbial metabolites, such as […]
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Metallomic Signatures
Metallomic Signatures
A metallomic signature is the condition-specific profile of trace metals and metal-binding molecules that reflects disrupted metal homeostasis.
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Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What was studied?
This original research study investigated whether the metallomic profile of dementia with Lewy bodies (DLB) differs from that of Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD). The study sought to determine if post-mortem changes in elemental concentrations—particularly in essential metals—could help differentiate these often-overlapping neurodegenerative conditions. Using ICP-MS (Inductively Coupled Plasma–Mass Spectrometry), the authors quantified concentrations of nine elements (Na, Mg, K, Ca, Mn, Fe, Cu, Zn, and Se) across 10 brain regions from DLB patients and age-/sex-matched controls. These findings were directly compared to previously published metallomic profiles for AD and PDD, produced using identical methodologies. Multivariate analyses (PCA and PLS-DA) were employed to assess the potential for disease discrimination based on metal signatures.
Who was studied?
The study analyzed post-mortem brain tissue from 23 DLB patients and 20 controls, collected across ten distinct brain regions. Comparative analyses included prior datasets from similarly matched AD and PDD patient cohorts.
What were the most important findings?
n this study, region-specific metallomic profiling revealed distinct trace element alterations in Dementia with Lewy Bodies (DLB). Copper (Cu) levels were consistently decreased in five of ten DLB brain regions, including the cingulate gyrus (CG), middle temporal gyrus (MTG), primary visual cortex (PVC), substantia nigra (SN), and putamen (PUT), suggesting a widespread Cu deficiency. Sodium (Na) was elevated in four regions—medulla (MED), cerebellum (CB), MTG, and CG—while more localized changes were observed for other metals. Iron (Fe) levels were increased in the motor cortex (MCX) and CG, whereas manganese (Mn) was decreased in both the PVC and MED. Calcium (Ca) was specifically reduced in the hippocampus, and selenium (Se) was also decreased in the PVC. No significant differences in magnesium, potassium, or zinc levels were observed between DLB and control brains. Multivariate analyses, including Principal Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA), demonstrated that DLB could be distinctly separated from Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD) based on metallomic signatures. Specifically, CG, MTG, and PVC profiles enabled discrimination between DLB and AD, while the PVC alone differentiated DLB from PDD. Notably, copper depletion emerged as the only common alteration across DLB, AD, and PDD, underscoring its potential central role in the pathogenesis of neurodegenerative diseases. The authors propose that these metallomic fingerprints may reflect disease-specific mechanisms, including variations in oxidative stress, protein aggregation, and mitochondrial dysfunction.
What are the greatest implications of this study?
This study provides compelling evidence that distinct metallomic signatures exist across DLB, AD, and PDD, despite shared pathology such as copper depletion. It strengthens the emerging concept that trace metal dysregulation is disease-specific, rather than a general byproduct of neurodegeneration. The findings support the idea that metallomic profiling—potentially via cerebrospinal fluid or advanced imaging in living patients—could improve differential diagnosis of dementias with overlapping clinical features. Furthermore, the study reinforces the hypothesis that metal dyshomeostasis, particularly copper depletion, may be a contributing pathogenic mechanism, impairing antioxidant defenses and mitochondrial function. These findings could inform new diagnostic tools and therapeutic targets.