Image: An ATR attachment for infrared spectroscopy. The sample is in the steel containers either side of the pink crystal (Photo courtesy of Wikimedia Commons).
Advanced spectroscopy methods were used to establish a direct diagnostic test for Alzheimer's disease and other types of neurodegenerative disorders.
Neurodegenerative diseases lack early and accurate diagnosis, and tests currently used for their detection are either invasive or expensive and time-consuming. A recent study used blood plasma to diagnose and differentiate various neurodegenerative diseases; the achieved sensitivities and specificities were equal to, or even higher than, the ones obtained by clinical/molecular methods.
In conducting this study, investigators at Lancaster University (United Kingdom) employed attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) combined with chemometric techniques to analyze blood plasma samples from a study population.
Attenuated total reflection (ATR) is a sampling technique used in conjunction with infrared spectroscopy, which enables samples to be examined directly in the solid or liquid state without further preparation. ATR uses a property of total internal reflection resulting in an evanescent wave. A beam of infrared light is passed through the ATR crystal in such a way that it reflects at least once off the internal surface in contact with the sample. This reflection forms the evanescent wave, which extends into the sample. The number of reflections may be varied by varying the angle of incidence. The beam is then collected by a detector as it exits the crystal. Most modern infrared spectrometers can be converted to characterize samples via ATR by mounting the ATR accessory in the spectrometer's sample compartment. Infrared (IR) spectroscopy by ATR is applicable to the same chemical or biological systems as the transmission method. One advantage of ATR-IR over transmission-IR, is the limited path length into the sample. This avoids the problem of strong attenuation of the IR signal in highly absorbing media, such as aqueous solutions.
For the recent study, blood samples were collected by conventional venipuncture, permitting repeated measurements from the same individuals to monitor their progression throughout the years or evaluate any tested drugs. The study population comprised 549 individuals: 347 with various neurodegenerative diseases and 202 age-matched healthy individuals. Alzheimer’s disease (AD; n = 164) was identified with 70% sensitivity and specificity, which after the incorporation of apolipoprotein epsilon-4 genotype (APOE epsilon-4) information, increased to 86% when individuals carried one or two alleles of epsilon-4, and to 72% sensitivity and 77% specificity when individuals did not carry epsilon-4 alleles.
Early AD cases (n = 14) were identified with 80% sensitivity and 74% specificity. Segregation of AD from dementia with Lewy bodies (DLB; n = 34) was achieved with 90% sensitivity and specificity. Other neurodegenerative diseases, such as frontotemporal dementia (FTD; n = 30), Parkinson’s disease (PD; n = 32), and progressive supranuclear palsy (PSP; n = 31), were included in the study population for diagnostic purposes. Thus, the method allowed for both rapid and robust diagnosis of neurodegeneration and segregation between different dementias.
Senior author Dr. Francis Martin, professor of biosciences at Lancaster University, said, "We have an aging population, meaning that the incidence and prevalence of Alzheimer's is increasing, as is the need for accurate diagnosis. The ability to identify different neurodegenerative diseases through the analysis of blood offers a faster and accurate way of establishing the most effective treatment plan as well as disease monitoring. For those suffering with Alzheimer's disease, the damage is already well advanced once conventionally diagnosed, but this new method offers a potentially effective early screening tool when patients are only demonstrating signs of mild cognitive impairment. This is a potentially significant breakthrough for the prevention of different debilitating and chronic neurological diseases."
The ATR-FTIR study was published in the September 5, 2017, online edition of the journal Proceedings of the [U.S.] National Academy of Sciences.