Potential Research Questions
How can neurodegenerative disease be detected early?
Can metabolomics help improve treatment stratification and outcomes?
Can biomarkers help to better characterize and treat psychiatric disorders?
Status Quo and Medical Need
In many neurological and psychiatric disorders, treatment options are limited, and frequently ineffective. This may in part be due to delayed diagnosis, while the suitability of diagnostic procedures and the suitability of therapeutic targets are also a matter of debate.
With Alzheimer’s disease being discussed as "Type 3 Diabetes", the acknowledgement that the gut-brain-axis is critically involved in Parkinson's disease, and the recent finding that the brain is connected to the lymphatic system, increasing interest in the systemic component of CNS disorders has evolved.
Biocrates has helped find the first biomarker signature in blood that may contribute to finding patients at risk of developing cognitive impairment or Alzheimer’s years before clinical manifestation, and is partner in major research consortia in the sector, such as the "Alzheimer’s disease neuroimaging (ADNI) metabolomics consortium".
Relevant Metabolite Classes
- Excess neurotransmitters may contribute to schizophrenia.
- Dysfunctional neurotransmission may cause neurons to become apoptotic, leading to neurodegeneration.
Phospho- and sphingolipids:
- Phospholipid metabolism seems to be involved in neurodegeneration.
- Sphingolipids form the myelin sheath of neurons.
- Mitochondrial dysfunction (reflected by acylcarnitines) seems to be an important pathophysiological mechanism, among other, in Alzheimer’s disease and multiple sclerosis.
- Mitochondria also seem to be playing a role in tissue damage in stroke.
- Cholesterol metabolism seems to be playing an important role in Alzheimer’s disease, and the risk gene ApoE is involved in cholesterol transport.
- Bile acids interact with the gut microbiome, which is connected to the CNS via the gut-brain-axis. The fact that a large number of microbial metabolites have been detected in CSF also indicates the importance of the microbiome for mental health.
- Toledo et al.: Metabolic network failures in Alzheimer's disease—A biochemical road map; Alzheimer's & Dementia 2017
- Skene et al.: Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers; Scientific Reports 2017
- Mapstone et al.: What success can teach us about failure: the plasma metabolome of older adults with superior memory and lessions for Alzheimer's Disease; Neurobiology of Aging 2016
- Casanova et al.: Blood metabolite markers of preclinical Alzheimer's disease in two longitudinally followed cohorts of older individuals; Alzheimer’s & Dementia 2016
- Cheng et al.: Metabolic Disturbances in Plasma as Biomarkers for Huntington’s Disease; J. Nutr. Biochem. 2016
- Rotroff et al.: Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants; Transl Psychiatry 2016
- Fiandaca et al.: Plasma 24-metabolite Panel Predicts Preclinical Transition to Clinical Stages of Alzheimer's Disease; Frontiers in neurology 2015
- Cermenati et al.: Lack of Sterol Regulatory Element Binding Factor-1c Imposes Glial Fatty Acid Utilization Leading to Peripheral Neuropathy; Cell Metabolism 2015
- Mapstone et al.: Plasma phospholipids identify antecedent memory impairment in older adults; Nature Medicine 2014
- He et al.: Schizophrenia shows a unique metabolomics signature in plasma; Translational Psychiatry 2012
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