Differentiating Frontotemporal Dementia Through Metabolomics

Researchers have investigated the plasma metabolite profile of patients with frontotemporal dementia (FTD) and Alzheimer’s disease (AD) using an untargeted metabolomic approach in combination with gas chromatography–mass spectrometry (GC–MS) (1).

Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by progressive impairment in behaviour, executive function, and language. It is one of the most common causes of neurocognitive disorder in people under 65 years old with around 10 in every 100,000 persons likely to be afflicted. The most common form of FTD is a behavioural variant (bvFTD), which is clinically different to atypical AD cases and which it can sometimes be mistaken for. Generally, survival is shorter and cognitive decline is faster than with typical AD cases. Therefore, a differential diagnosis between bvFTD and atypical AD cases is crucial.

Currently, to differentiate between bvFTD and AD cases requires an evaluation of cognition and cerebrospinal fluid (CSF) biomarkers as well as a neuroimaging investigation and genetic mutations screening; however, an accurate diagnosis still poses a clinical challenge in specific cases. Furthermore, the collection of CSF requires an invasive lumbar puncture procedure, access to molecular neuroimaging methods can be restricted, and no blood biomarkers have been identified.

An alternative to diagnosis through these methods could come with the investigation of metabolites by Tsuruoka et al. (2), who identified six serum metabolites that were significantly increased in patients with dementia as well as 45 additional metabolites identified as candidate markers that could discriminate patients with dementia from cognitively healthy controls. As such, researchers aimed to investigate the plasma metabolite profile of patients with bvFTD compared to AD patients and cognitively healthy individuals using an untargeted metabolomic approach, with hopes to identify biological mechanisms and possible biomarkers for bvFTD diagnosis.

Results found a reduction in the levels of palmitoleic, oleic, and lauric acids in the bvFTD group compared to the AD group, however, no significance after multiple comparison correction was observed. Reduced levels of creatinine, glycine, tryptophan, uric acid, hypoxanthine, serine, valine, threonine, isoleucine, homoserine,methionine, glutamic acid, capric acid, tartronic acid, fumaric acid, and myoinositol, metabolites related to glycine/serine/threonine, alanine/aspartate/glutamate pathways and aminoacyl-tRNA biosynthesis, were also found in the bvFTD group when compared to controls. This led researchers to theorize that bvFTD patients may present an impairment of amino acid metabolism and the translation process.

Researchers hope this study can encourage further and more robust studies to fully explore the possibility of biomarkers for the diagnosis of this dementia form.—L.B.

References

1. A.L.M. Santos, J.G. Vitório, M.J.N. de Paiva et al., J. Pharm. Biomed. Anal. 189, 113424 (2020).
2. M. Tsuruoka et al., Electrophoresis 1, 2865–2872 (2013).