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Does Shining Laser Light on Blood Reflect Alzheimer’s?

Series - American Neurological Association: 2014 Annual Meeting:

Researchers have been trying, with limited success, to pinpoint blood markers that herald Alzheimer’s. At the 139th annual meeting of the American Neurological Association, held October 12-14 in Baltimore, one presentation suggested that a laser-based measurement can do the job. In Raman spectroscopy, researchers shine laser light at a sample and measure the energies of the scattered photons. The spectrum that emerges depends on the molecules in the sample with which the photons interact. Taking Raman spectra of blood samples, researchers led by Igor Lednev, University at Albany, State University of New York, and Earl Zimmerman, Albany Medical Center, distinguished people with Alzheimer’s disease from healthy controls, and from people with other forms of dementia. “We don’t limit our search to a specific class of biomolecule,” Lednev told Alzforum. “It could be picking up a specific protein, or equally multiple components.” The results appeared in online in the Journal of Biophotonics on September 25.

When laser light hits a sample, some photons bounce back. Most return unchanged, but a tiny fraction lose some energy by causing molecules in the sample to vibrate. The difference in energy is known as the Raman shift, and varies depending on the electron properties and bonds in the molecules the photons encounter. Every molecule has its own unique Raman spectrum, or “fingerprint.” Raman spectroscopy is used to identify the chemical structure and composition of solids, liquids, and gases. It has also been explored as a way to analyze blood for breast cancer, pre-eclampsia, oxidative stress, and low glucose (see Pichardo-Molina et al., 2007; Schipper et al., 2008; Koo et al., 1999). Researchers led by Pedro Carmona, Instituto de Estructura de la Materia, CSIC, Madrid, have reported that it differentiated blood samples of 35 Alzheimer’s patients from those of 12 healthy controls with about 92 percent specificity and 89 percent sensitivity (see Carmona et al., 2013). Others have reported similar success on small numbers of patient as well (Burns et al., 2009; Peuchant et al., 2008).

Lednev and colleagues wanted to know if the technology could also distinguish AD from other forms of dementia. First author Elena Ryzhikova aimed a faint laser beam of near-infrared photons at blood samples from 18 healthy controls, 10 patients each with mild and moderate AD, and 18 people who had other forms of dementia, including two with progressive supranuclear palsy, 10 with dementia due to Parkinson’s disease, five who had dementia with Lewy bodies, and three with frontotemporal dementia.

Blood contains many different proteins, lipids, and carbohydrates. Raman spectra reflect that complexity, showing dozens of peaks and troughs. The researchers used a series of computer programs to determine which spectral features best separated people with AD from healthy controls or from people with other dementias. The algorithms distinguished mild or moderate Alzheimer’s from healthy controls and people with other dementias with about 95 percent accuracy. “The data were surprisingly good in terms of their ability to differentiate stages of AD from healthy people and other dementias," said David Teplow, University of California, Los Angeles.

Though the technique does not identify individual blood components that distinguish AD spectra from others, most of the spectral peaks arise when photons interact with proteins, as opposed to lipids, DNA, or other molecules that may be floating around in the blood. “We can conclude that the composition of these blood samples differs in protein makeup,” said Lednev. In the future, he plans to validate this test in a larger cohort of patients and look for the effects of additional factors, such as patient medication, and other illnesses. Preliminary evidence suggests measurements are unaffected by the AD drug donepezil, which is taken by many AD patients and ends up in their blood. To see if this method picks up evidence of AD in the presymptomatic phase, Lednev will also analyze blood samples given by patients five to 10 years before they developed symptoms.

While the ideal test would pinpoint the exact biomolecular changes taking place in a person with AD, that is not essential, Teplow said “It is more important that they can differentiate one patient group from another,” he told Alzforum. While the study used only a small number of patients, and needs to be validated with a larger sample set, Teplow noted that the new test is unbiased, which is a potential advantage over other methods that reach similar sensitivity and specificity. That is especially true if it could help tell one type of dementia from another, he said.

Though some scientists expressed skepticism that a blood test of any kind is in the cards for AD, Carmona told Alzforum that the routine clearance of cerebrospinal fluid solutes into the blood makes the latter a potential source of biomarkers. “Infrared and Raman spectroscopy are rapid, reagent-free, non-destructive, high-throughput, and relatively inexpensive methods that require a minimal amount of background training,” he wrote in an email.—Gwyneth Dickey Zakaib

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References

Paper Citations

  1. Pichardo-Molina JL, Frausto-Reyes C, Barbosa-García O, Huerta-Franco R, González-Trujillo JL, Ramírez-Alvarado CA, Gutiérrez-Juárez G, Medina-Gutiérrez C. Raman spectroscopy and multivariate analysis of serum samples from breast cancer patients. Lasers Med Sci. 2007 Nov;22(4):229-36. Epub 2007 Feb 13 PubMed.
  2. Schipper HM, Kwok CS, Rosendahl SM, Bandilla D, Maes O, Melmed C, Rabinovitch D, Burns DH. Spectroscopy of human plasma for diagnosis of idiopathic Parkinson's disease. Biomark Med. 2008 Jun;2(3):229-38. PubMed.
  3. Koo TW, Berger AJ, Itzkan I, Horowitz G, Feld MS. Reagentless blood analysis by near-infrared Raman spectroscopy. Diabetes Technol Ther. 1999;1(2):153-7. PubMed.
  4. Carmona P, Molina M, Calero M, Bermejo-Pareja F, Martínez-Martín P, Toledano A. Discrimination analysis of blood plasma associated with Alzheimer's disease using vibrational spectroscopy. J Alzheimers Dis. 2013;34(4):911-20. PubMed.
  5. Burns DH, Rosendahl S, Bandilla D, Maes OC, Chertkow HM, Schipper HM. Near-infrared spectroscopy of blood plasma for diagnosis of sporadic Alzheimer's disease. J Alzheimers Dis. 2009;17(2):391-7. PubMed.
  6. Peuchant E, Richard-Harston S, Bourdel-Marchasson I, Dartigues JF, Letenneur L, Barberger-Gateau P, Arnaud-Dabernat S, Daniel JY. Infrared spectroscopy: a reagent-free method to distinguish Alzheimer's disease patients from normal-aging subjects. Transl Res. 2008 Sep;152(3):103-12. PubMed.

Further Reading

Papers

  1. Ramachandran G, Milán-Garcés EA, Udgaonkar JB, Puranik M. Resonance Raman spectroscopic measurements delineate the structural changes that occur during tau fibril formation. Biochemistry. 2014 Oct 21;53(41):6550-65. Epub 2014 Oct 6 PubMed.
  2. Deckert-Gaudig T, Kämmer E, Deckert V. Tracking of nanoscale structural variations on a single amyloid fibril with tip-enhanced Raman scattering. J Biophotonics. 2012 Mar;5(3):215-9. PubMed.

Primary Papers

  1. Ryzhikova E, Kazakov O, Halamkova L, Celmins D, Malone P, Molho E, Zimmerman EA, Lednev IK. Raman spectroscopy of blood serum for Alzheimer's disease diagnostics: specificity relative to other types of dementia. J Biophotonics. 2014 Sep 25;9999(9999) PubMed.

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