Could a Skin Biopsy Diagnose LBD?

Could a skin biopsy diagnose LBD?

New research suggests skin biopsies may hold strong potential to help diagnose dementia with Lewy bodies (DLB). The study reveals two important changes associated with DLB can be seen in the skin. Deposits of alphasynuclein (a-syn), the protein that misfolds to become Lewy bodies, are found in the skin of people living with DLB. And there is a loss of the nerve function in the skin as well, which may contribute to the autonomic symptoms common in DLB.

Vincenzo Donadio, MD, PhD of IRCCS Institute of Neuroscience of Bologna, Italy, and a team of researchers studied 18 people who met the clinical criteria for DLB. The subjects also had biomarker test results or clinical symptoms highly suggestive of the presence of Lewy bodies in the brain. None had a family history of dementia or parkinsonism.

For comparison, 23 subjects were also studied who had dementia caused by other diseases. The group was called the non-synucleinopathy dementia group (NSD). Participants included 13 people with Alzheimer’s disease (AD), 6 with frontotemporal dementia (FTD), and 6 with vascular dementia. All diagnoses were supported by biomarker test results reflecting the relevant disorder. The study also included 25 age-matched health adults as control subjects.

The three groups had no significant differences in age or sex. The disease duration for the DLB and NSD groups was comparable, as was the degree of cognitive impairment.

Two skin biopsies were taken from each participant, including a) skin from the cervical section of the upper back and b) skin from the thigh and/or lower leg. These samples were then studied for a-syn deposits.

What the Biopsies Revealed

Analysis of the skin samples revealed that every person in the DLB group had a-syn deposits in at least one sample. Combining all samples taken from the DLB group, abnormal deposits were found in 75% of the samples. In comparison, none were found in any skin samples of the healthy control or NSD group.

There were some interesting variances within the DLB group.

  • Nearly all subjects who had autonomic dysfunction had a-syn deposits in all of their samples collected (97%), compared to those without autonomic symptoms (71%).
  • Per DLB subject, the number of samples with A-syn deposits was more associated with higher levels of parkinsonism

There were no differences within the DLB group associated age of disease onset, duration of disease, cognitive scores, which DLB symptom presented first – dementia or parkinsonism, and those receiving or not receiving treatment with levodopa.

Skin nerve functions were intact in the healthy control group and relatively preserved in the NSD group. In comparison the DLB group showed poor skin nerve supply, particularly in the thigh/leg. It is well documented that cardiac nerve supply is so frequently abnormal in DLB that it is part of the diagnostic criteria.

A Cautionary Note

Authors of an accompanying editorial, Ron Postuma, MD and Zuzana Walker, MD, caution readers of limitations of this study, including the fact that the DLB cohort was younger on average than a typical person with DLB. The same was true for the AD group. Lastly, Postuma and Walker indicate that rarely do studies demonstrate 100% positive results in one group and 100% negative in a comparison group. Replication of this study is needed in more representative cohorts in order to understand the potential for skin biopsies in diagnosing DLB.

The Bottom Line

If the results of this study can be replicated by other researchers in a larger study of people with DLB, skin biopsies have the potential to be a highly reliable biomarker for LBD. This would prove to be a powerful tool in clinical trials for disease-modifying therapies.

This study was published in July, 2017 in Neurology and was not supported by any targeted funding.