Metabolomics in Alzheimer's Disease: Pathogenesis and Sample Types
Alzheimer's Disease (AD) is a progressive neurodegenerative condition with a subtle onset. Clinically, it manifests through a range of dementia symptoms, including memory impairment, aphasia, apraxia, agnosia, visuospatial skill impairment, executive dysfunction, and personality and behavioral changes. Epidemiological studies have indicated that the incidence of Alzheimer's disease increases with age.
Pathogenesis of AD
Understanding the pathogenesis of AD is challenging, as it remains incompletely understood. A video (Inside Alzheimer's disease) released by the journal Nature Neuroscience in 2017 briefly outlines the two primary hypotheses regarding AD's pathogenesis: the amyloid-β (Aβ) and tau protein hypotheses.
1) Aβ Cascade Hypothesis: This theory proposes that β-secretase cleaves to produce sAPPβ protein, releasing it into the extracellular space. Subsequently, γ-secretase cleaves to produce Aβ peptides and β-amyloid precursor protein intracellular domains. The Aβ peptides accumulate in the brain's extracellular space, leading to the formation of Aβ senile plaques, a significant contributor to neuronal damage and death.
2) Tau Protein Abnormal Phosphorylation Hypothesis: In AD patients' brains, highly phosphorylated tau protein transitions from a soluble to an insoluble form, forming aggregates. This alteration not only disrupts its microtubule structure and normal function but also results in the dysfunction of synaptic proteins and the formation of neurofibrillary tangles.
Sample Types Suitable for AD Metabolism Studies
Metabolomics, which allows the measurement of metabolites at specific times, offers a valuable tool for understanding the dynamic response of AD patients to various stimuli and their changing physiological status. Thus, metabolomics can aid in the identification of diagnostic markers for Alzheimer's disease. Regarding suitable sample types for AD metabolism studies, brain tissue provides the most informative data, but it is not accessible in living patients, limiting its practicality for widespread biomarker detection. As a result, researchers are turning their attention to samples obtainable from circulating body fluids, including:
- Cerebrospinal Fluid (CSF): CSF is widely used but requires an invasive procedure performed by a doctor, making it challenging for large-scale screening.
- Plasma: Plasma is a convenient sample source for AD research, representing the entire body system. However, the blood-brain barrier may limit its ability to reflect brain metabolism, and variations in blood plasma metabolism based on factors like gender, age, and race have been observed. Many studies now combine plasma with other sample types.
- Urine: Urine is non-invasive, sterile, and easy to collect. However, it primarily contains hydrophilic metabolites, with lower concentrations of lipids and non-polar metabolites. Given the focus on lipid metabolism in AD research, urine may not be the most suitable source for AD biomarkers.
- Saliva: Saliva is easy to obtain, but AD patients often experience reduced saliva flow and dry mouth, making sample collection challenging.
- Fecal Samples: Fecal samples can partially reflect brain metabolism due to the gut-brain axis and are relatively easy to obtain. They are particularly favored when investigating AD from the perspective of gut microbiota.
In conclusion, cerebrospinal fluid, serum, plasma, and fecal samples are recommended as suitable sample types for AD studies, each with its unique advantages and limitations. More information about metabolomics samples can be viewed on Sample Requirements. MetwareBio has extensive experience in metabolomics detection and analysis. Our lab in Boston can provide you with TM Widely-Targeted Metabolomics, Quantitative Lipidomics, targeted metabolomics services, and more to support your AD Studies.
