The most common cause of dementia is Alzheimer’s disease, but it can be definitively diagnosed only after death, with a brain tissue biopsy. Earlier detection has been difficult because Alzheimer’s comprises complex symptoms and genetic changes, unlike diseases caused by a single gene, such as Huntington’s. In those cases, diagnostic tests have just one gene, or biomarker, to target. In contrast, a diagnostic test for Alzheimer’s would need to encompass a multitude of genetic causes, many of which are still unknown. A test is now within reach, thanks to the efforts of a Berkeley Lab team led by Biosciences Area Senior Scientist Cynthia McMurray.
The team has found a way to determine the chemical signature of Alzheimer’s disease, using a method called spectral phenotyping. They developed the technique with infrared microscopy using a benchtop source at the Advanced Light Source.
“The actual physical phenomenon that we’re measuring with infrared light is the vibrational states of molecules in the cell,” said McMurray. This generated a chemical profile of diseased samples that is so distinct from healthy cell samples that McMurray likens the process to “cellular fingerprinting.”
“Since each cell has subtly different amounts of each biomolecule, we can use the spectra to identify the cell type and if it has signatures of disease states,” added ALS Photon Science Operations Group Leader Mike Martin.
Though spectral phenotyping worked in brain cells, “directly accessing brain cells in humans is not easy nor desired,” Martin pointed out. The researchers proceeded to test the limits of the technique.
“One of the big surprises was just how discriminating it was,” said McMurray. “What we discovered is you don’t need to use a brain cell to track disease because the skin cells are affected in their own way.”
Because this new test can detect changes early, before patients start exhibiting Alzheimer’s symptoms, and in more accessible tissue, the researchers hope that spectral phenotyping will give patients better options in the future.
“Once spectral signatures are found that correlate to disease type and progression, we can implement laser-based infrared spectroscopies together with advanced computational analysis in a variety of medical settings,” said Martin.
L. Lovergne, D. Ghosh, R. Schuck, A.A. Polyzos, A.D. Chen, M.C. Martin, E.S. Barnard, J.B. Brown, and C.T. McMurray, “An infrared spectral biomarker accurately predicts neurodegenerative disease class in the absence of overt symptoms,” Sci. Rep. 11, 15598 (2021), doi: 10.1038/s41598-021-93686-8.
Adapted from the Berkeley Lab news release, “Cell Fingerprinting Could Yield Long-Awaited Alzheimer’s Disease Diagnostic.”