A unique ratio of metabolites measured in blood may help supplement a clinical diagnosis of early Alzheimer’s disease, allowing for earlier intervention, early research suggests.
Investigators found that plasma concentrations of 2-aminoethyl dihydrogen phosphate and taurine could distinguish adults with early-stage Alzheimer’s disease from cognitively normal adults.
“Our biomarker for early-stage Alzheimer’s disease represents new thinking and is unique from the amyloid-beta and p-tau molecules that are currently being investigated to diagnose AD,” Sandra Banack, PhD, senior scientist, Brain Chemistry Labs, Jackson, Wyoming, told Medscape Medical News.
If further studies pan out, Banack said this biomarker could “easily be transformed into a test to aid clinical evaluations for Alzheimer’s disease.”
The study was published online April 21 in PLOS ONE.
New Drug Target?
The researchers measured concentrations of 2-aminoethyl dihydrogen phosphate and taurine in blood plasma samples in 25 patients (21 men; mean age, 71) with a clinical diagnosis of early-stage Alzheimer’s based on a Clinical Dementia Rating (CDR) score of 0.5, suggesting very mild cognitive impairment, and 25 healthy controls (20 men; mean age, 39).
The concentration of 2-aminoethyl dihydrogen phosphate, normalized by the concentration of taurine, reliably distinguished blood samples of early-stage Alzheimer’s patients from controls in a blinded analysis.
This biomarker “could lead to new understanding of AD disease and lead to new drug candidates,” Banack told Medscape Medical News.
The researchers note that 2-aminoethyl dihydrogen phosphate plays an important role in the structure and function of cellular membranes.
Physiologic effects of increased 2-aminoethyl dihydrogen phosphate concentrations in the blood are not known. However, in one study, concentrations of this molecule were found to be significantly lower in the temporal cortex, frontal cortex and hippocampus (40%) in patients with Alzheimer’s disease compared with controls.
“New biomarkers take time before they can be implemented in the clinic. The next step will be to repeat the experiments using a large sample size of AD patient blood samples,” Banack told Medscape Medical News.
The study team is looking to source a larger sample size of AD blood samples to replicate these findings. They are also examining this biomarker relative to other neurodegenerative diseases.
“If verified with larger sample sizes, the quantification of 2-aminoethyl dihydrogen phosphate could potentially assist in the diagnosis of early-stage Alzheimer’s disease when used in conjunction with the patient’s CDR score and other potential AD biomarkers,” Banack and colleagues say.
Caveats, Cautionary Notes
Commenting on the findings for Medscape Medical News, Rebecca M. Edelmayer, PhD, Alzheimer’s Association senior director of scientific engagement, said the study is “interesting, though very small-scale and very preliminary.”
Edelmayer said one “major limitation” is that participants did not have their Alzheimer’s diagnosis confirmed with “gold standard biomarkers. They have been diagnosed based only on their cognitive and behavioral symptoms.”
She also cautioned that the study population is not representative — either of the general public or people living with Alzheimer’s disease.
For example, 41 out of all 50 samples are from men, “though we know women are disproportionately impacted by Alzheimer’s.”
“There is a mismatch in the age of the study groups,” Edelmayer noted. The mean age of controls in the study was 39 and the mean age of people with dementia was 71. Race or ethnicity and other demographic information is also unclear from the article.
“There is an urgent need for simple, inexpensive, noninvasive and easily available diagnostic tools for Alzheimer’s, such as a blood test. A simple blood test for Alzheimer’s would be a great advance for individuals with — and at risk for — the disease, families, doctors, and researchers,” Edelmayer said.
“Bottom line,” Edelmayer continued, “these results need to be further tested and verified in long-term, large-scale studies with diverse populations that are representative of those living with Alzheimer’s disease.”
This research was supported by the William Stamps Farish Fund and the Josephine P. & John J. Louis Foundation. Brain Chemistry Labs has applied for a patent related to this research. Edelmayer has no relevant disclosures.
PLOS ONE. Published online April 21, 2022. Full text