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Total alpha synuclein and oligomeric synuclein may discriminate between tears of patients with Parkinson’s disease and those of healthy controls.

LOS ANGELES—Tears may hold diagnostic clues as to whether someone has Parkinson’s disease, according to a preliminary study presented at the American Academy of Neurology’s 70th Annual Meeting. “We believe our research is the first to show that tears may be a reliable, inexpensive, and noninvasive biologic marker of Parkinson’s disease,” said study author Mark Floyd Lew, MD, Professor of Clinical Neurology, and Joseph P. Van Der Meulen, MD, Chair in Parkinson’s Disease Research in Honor of Robert J. Pasarow, and Vice Chair, in the Department of Neurology at the Keck School of Medicine of the University of Southern California in Los Angeles.

Mark Floyd Lew, MD

Nonmotor features of Parkinson’s disease occur years prior to motor dysfunction and represent a well-suited platform to investigate for a possible biomarker. Lacrimal glands are highly innervated by cholinergic neurons, and tear fluid secreted by lacrimal glands is greatly stimulated by cholinergic neurons. The production, packaging, and secretion of specific proteins into tears may be regulated by changes in nerve function to lacrimal glands. According to the researchers, analysis of any alteration in the secretion of proteins into tears may identify a reliable and noninvasive biomarker for Parkinson’s disease.

For the study, tear samples were collected from 55 patients with Parkinson’s disease of varying severity and 27 age- and gender-matched controls without Parkinson’s disease. In addition, tears were analyzed for the levels of four proteins—total alpha synuclein, CC chemokine ligand 2 (CCL-2), DJ-1 (Parkinson’s disease protein 7), and oligomeric alpha synuclein.

The researchers found differences in the levels of a total alpha-synuclein in the tears of patients with Parkinson’s disease, compared with those of controls. Additionally, levels of oligomeric alpha-synuclein, which is alpha-synuclein that has formed aggregates that are implicated in nerve damage in Parkinson’s disease, were also significantly different, compared with controls. It is also possible that the tear gland secretory cells themselves produce these different forms of alpha-synuclein that can be directly secreted into tears, the researchers said.

Total levels of alpha-synuclein were decreased in patients with Parkinson’s disease, with an average of 423 picograms of that protein per milligram (pg/mg) compared with 704 pg/mg in healthy controls. However, levels of oligomeric alpha-synuclein were increased in patients with Parkinson’s disease, with an average of 1.45 nanograms per milligram of tear protein (ng/mg), compared with 0.27 ng/mg in controls. While detectable in tears, neither CCL-2 nor DJ-1 varied between patients with Parkinson’s disease and controls.

“Knowing that something as simple as tears could help neurologists differentiate between people who have Parkinson’s disease and those who do not in a noninvasive manner is exciting,” said Dr. Lew. “And because the Parkinson’s disease process can begin years or decades before symptoms appear, a biologic marker like this could be useful in diagnosing, or even treating, the disease earlier.”

More research needs to be done in larger groups of people to investigate whether these protein changes can be detected in tears in the earliest presymptomatic stages of the disease, said the researchers.

The study was supported by the Michael J. Fox Foundation for Parkinson’s Research and the Plotkin Foundation.NR

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Total alpha synuclein and oligomeric synuclein may discriminate between tears of patients with Parkinson’s disease and those of healthy controls.
Total alpha synuclein and oligomeric synuclein may discriminate between tears of patients with Parkinson’s disease and those of healthy controls.

LOS ANGELES—Tears may hold diagnostic clues as to whether someone has Parkinson’s disease, according to a preliminary study presented at the American Academy of Neurology’s 70th Annual Meeting. “We believe our research is the first to show that tears may be a reliable, inexpensive, and noninvasive biologic marker of Parkinson’s disease,” said study author Mark Floyd Lew, MD, Professor of Clinical Neurology, and Joseph P. Van Der Meulen, MD, Chair in Parkinson’s Disease Research in Honor of Robert J. Pasarow, and Vice Chair, in the Department of Neurology at the Keck School of Medicine of the University of Southern California in Los Angeles.

Mark Floyd Lew, MD

Nonmotor features of Parkinson’s disease occur years prior to motor dysfunction and represent a well-suited platform to investigate for a possible biomarker. Lacrimal glands are highly innervated by cholinergic neurons, and tear fluid secreted by lacrimal glands is greatly stimulated by cholinergic neurons. The production, packaging, and secretion of specific proteins into tears may be regulated by changes in nerve function to lacrimal glands. According to the researchers, analysis of any alteration in the secretion of proteins into tears may identify a reliable and noninvasive biomarker for Parkinson’s disease.

For the study, tear samples were collected from 55 patients with Parkinson’s disease of varying severity and 27 age- and gender-matched controls without Parkinson’s disease. In addition, tears were analyzed for the levels of four proteins—total alpha synuclein, CC chemokine ligand 2 (CCL-2), DJ-1 (Parkinson’s disease protein 7), and oligomeric alpha synuclein.

The researchers found differences in the levels of a total alpha-synuclein in the tears of patients with Parkinson’s disease, compared with those of controls. Additionally, levels of oligomeric alpha-synuclein, which is alpha-synuclein that has formed aggregates that are implicated in nerve damage in Parkinson’s disease, were also significantly different, compared with controls. It is also possible that the tear gland secretory cells themselves produce these different forms of alpha-synuclein that can be directly secreted into tears, the researchers said.

Total levels of alpha-synuclein were decreased in patients with Parkinson’s disease, with an average of 423 picograms of that protein per milligram (pg/mg) compared with 704 pg/mg in healthy controls. However, levels of oligomeric alpha-synuclein were increased in patients with Parkinson’s disease, with an average of 1.45 nanograms per milligram of tear protein (ng/mg), compared with 0.27 ng/mg in controls. While detectable in tears, neither CCL-2 nor DJ-1 varied between patients with Parkinson’s disease and controls.

“Knowing that something as simple as tears could help neurologists differentiate between people who have Parkinson’s disease and those who do not in a noninvasive manner is exciting,” said Dr. Lew. “And because the Parkinson’s disease process can begin years or decades before symptoms appear, a biologic marker like this could be useful in diagnosing, or even treating, the disease earlier.”

More research needs to be done in larger groups of people to investigate whether these protein changes can be detected in tears in the earliest presymptomatic stages of the disease, said the researchers.

The study was supported by the Michael J. Fox Foundation for Parkinson’s Research and the Plotkin Foundation.NR

LOS ANGELES—Tears may hold diagnostic clues as to whether someone has Parkinson’s disease, according to a preliminary study presented at the American Academy of Neurology’s 70th Annual Meeting. “We believe our research is the first to show that tears may be a reliable, inexpensive, and noninvasive biologic marker of Parkinson’s disease,” said study author Mark Floyd Lew, MD, Professor of Clinical Neurology, and Joseph P. Van Der Meulen, MD, Chair in Parkinson’s Disease Research in Honor of Robert J. Pasarow, and Vice Chair, in the Department of Neurology at the Keck School of Medicine of the University of Southern California in Los Angeles.

Mark Floyd Lew, MD

Nonmotor features of Parkinson’s disease occur years prior to motor dysfunction and represent a well-suited platform to investigate for a possible biomarker. Lacrimal glands are highly innervated by cholinergic neurons, and tear fluid secreted by lacrimal glands is greatly stimulated by cholinergic neurons. The production, packaging, and secretion of specific proteins into tears may be regulated by changes in nerve function to lacrimal glands. According to the researchers, analysis of any alteration in the secretion of proteins into tears may identify a reliable and noninvasive biomarker for Parkinson’s disease.

For the study, tear samples were collected from 55 patients with Parkinson’s disease of varying severity and 27 age- and gender-matched controls without Parkinson’s disease. In addition, tears were analyzed for the levels of four proteins—total alpha synuclein, CC chemokine ligand 2 (CCL-2), DJ-1 (Parkinson’s disease protein 7), and oligomeric alpha synuclein.

The researchers found differences in the levels of a total alpha-synuclein in the tears of patients with Parkinson’s disease, compared with those of controls. Additionally, levels of oligomeric alpha-synuclein, which is alpha-synuclein that has formed aggregates that are implicated in nerve damage in Parkinson’s disease, were also significantly different, compared with controls. It is also possible that the tear gland secretory cells themselves produce these different forms of alpha-synuclein that can be directly secreted into tears, the researchers said.

Total levels of alpha-synuclein were decreased in patients with Parkinson’s disease, with an average of 423 picograms of that protein per milligram (pg/mg) compared with 704 pg/mg in healthy controls. However, levels of oligomeric alpha-synuclein were increased in patients with Parkinson’s disease, with an average of 1.45 nanograms per milligram of tear protein (ng/mg), compared with 0.27 ng/mg in controls. While detectable in tears, neither CCL-2 nor DJ-1 varied between patients with Parkinson’s disease and controls.

“Knowing that something as simple as tears could help neurologists differentiate between people who have Parkinson’s disease and those who do not in a noninvasive manner is exciting,” said Dr. Lew. “And because the Parkinson’s disease process can begin years or decades before symptoms appear, a biologic marker like this could be useful in diagnosing, or even treating, the disease earlier.”

More research needs to be done in larger groups of people to investigate whether these protein changes can be detected in tears in the earliest presymptomatic stages of the disease, said the researchers.

The study was supported by the Michael J. Fox Foundation for Parkinson’s Research and the Plotkin Foundation.NR

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Neurology Reviews - 26(6)
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