Charles H Adler1, Geidy E Serrano2, Nan Zhang3, Michael L Hinni4, David G Lott4, Shyamal H Mehta5, Lucia I Sue2, Anthony Intorcia2, Thomas G Beach2. 1. Parkinson's Disease and Movement Disorders Center, Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic, Scottsdale, AZ, USA. Electronic address: cadler@mayo.edu. 2. Banner Sun Health Research Institute, Sun City, AZ, USA. 3. Department of Biostatistics, Mayo Clinic College of Medicine, Mayo Clinic, Scottsdale, AZ, USA. 4. Department of Otolaryngology, Mayo Clinic, Phoenix, AZ, USA. 5. Parkinson's Disease and Movement Disorders Center, Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic, Scottsdale, AZ, USA.
Abstract
INTRODUCTION: Submandibular gland (SMG) biopsies detect pathological alpha-synuclein (aSyn) in patients with Parkinson's disease (PD). The objectives of this study were to determine 1) the feasibility of performing a second SMG biopsy in previously biopsied patients, 2) the feasibility of doing bilateral SMG biopsies, 3) laterality of aSyn density, 4) whether aSyn density changes over time. METHODS: Seven PD patients (6 males) previously having positive unilateral SMG biopsies underwent bilateral needle biopsies. Staining with a validated antibody to pathologic p-serine 129 aSyn was performed. RESULTS: Mean age at time of second biopsy was 76 years and mean time between biopsies was 4.1 years. Five subjects had sufficient SMG tissue bilaterally and two only unilaterally for a total of 12/14 glands biopsied having sufficient tissue, all 7 subjects having sufficient tissue on at least one side, and all 12 glands being aSyn positive. There was a 4x increase in aSyn density on average in the repeat biopsy, with 5 subjects having an increase, one no change, and one a decrease in density. Side effects were similar to previous reports; mainly bruising, swelling, slight bleeding. CONCLUSIONS: This is the first published study of bilateral transcutaneous needle biopsies of the SMG in living patients with PD which showed better tissue acquisition and a change in aSyn density over time. While further study is needed, there is potential for SMG biopsies to serve as a tissue biomarker for PD disease progression and potentially as a peripheral outcome measure for anti-aSyn treatment.
INTRODUCTION: Submandibular gland (SMG) biopsies detect pathological alpha-synuclein (aSyn) in patients with Parkinson's disease (PD). The objectives of this study were to determine 1) the feasibility of performing a second SMG biopsy in previously biopsied patients, 2) the feasibility of doing bilateral SMG biopsies, 3) laterality of aSyn density, 4) whether aSyn density changes over time. METHODS: Seven PDpatients (6 males) previously having positive unilateral SMG biopsies underwent bilateral needle biopsies. Staining with a validated antibody to pathologic p-serine 129 aSyn was performed. RESULTS: Mean age at time of second biopsy was 76 years and mean time between biopsies was 4.1 years. Five subjects had sufficient SMG tissue bilaterally and two only unilaterally for a total of 12/14 glands biopsied having sufficient tissue, all 7 subjects having sufficient tissue on at least one side, and all 12 glands being aSyn positive. There was a 4x increase in aSyn density on average in the repeat biopsy, with 5 subjects having an increase, one no change, and one a decrease in density. Side effects were similar to previous reports; mainly bruising, swelling, slight bleeding. CONCLUSIONS: This is the first published study of bilateral transcutaneous needle biopsies of the SMG in living patients with PD which showed better tissue acquisition and a change in aSyn density over time. While further study is needed, there is potential for SMG biopsies to serve as a tissue biomarker for PD disease progression and potentially as a peripheral outcome measure for anti-aSyn treatment.
Authors: Maxim Signaevsky; Bahram Marami; Marcel Prastawa; Nabil Tabish; Megan A Iida; Xiang Fu Zhang; Mary Sawyer; Israel Duran; Daniel G Koenigsberg; Clare H Bryce; Lana M Chahine; Brit Mollenhauer; Sherri Mosovsky; Lindsey Riley; Kuldip D Dave; Jamie Eberling; Chris S Coffey; Charles H Adler; Geidy E Serrano; Charles L White; John Koll; Gerardo Fernandez; Jack Zeineh; Carlos Cordon-Cardo; Thomas G Beach; John F Crary Journal: Acta Neuropathol Commun Date: 2022-02-14 Impact factor: 7.801