Prevalence Of Lewy-Type Synucleinopathy In The Submandibular Gland Of Subjects With Neuropathologically-Confirmed Dementia With Lewy Bodies. (S38.007)

Objective: Determine whether the prevalence of Lewy-type α-synucleinopathy (LTS) in autopsied submandibular glands from subjects with dementia with Lewy bodies (DLB) might be sufficiently high to consider submandibular gland biopsy as a new diagnostic method. Background: The clinical diagnosis of DLB is missed in up to 70% of subjects as the classical clinical syndrome is often absent. We have previously shown that LTS is reliably present in the submandibular gland in autopsied subjects with Parkinson’s disease (PD) and that needle core biopsy of the submandibular gland, in a pilot study in living PD subjects, has high diagnostic sensitivity for PD. Methods: Sections of large segments of the submandibular gland (0.8 - 1.5 cm2) were immunohistochemically stained for LTS from 123 autopsied subjects: controls (n=50), DLB (n=23), incidental Lewy body disease (ILBD) (n=7), Alzheimer disease with (n=28) and without (n=15) LTS in the brain. Results: Submandibular gland LTS was found in 16/23 (69%) of these DLB subjects. No control had LTS. Of the AD cases with brain LTS, 4/28 (14%) had LTS in the submandibular gland while none of the other AD cases had LTS. None of the 7 ILBD subjects had LTS in the submandibular gland. The DLB cases without submandibular gland LTS tended to have lower total brain LTS loads (mean LTS load 30.7 vs 23.0; p = 0.06). Conclusions: These results suggest that, analogously to what we have found for PD subjects, that in vivo needle biopsy of the submandibular gland may be a feasible means of diagnosing DLB with greatly improved diagnostic sensitivity. This would be particularly advantageous for identifying DLB subjects for clinical trials and for identifying, in AD clinical trials, those subjects with concurrent AD and DLB. Additionally, submandibular needle gland biopsy could potentially be used as a gold standard for other biomarker studies. Disclosure: Dr. Beach has received personal compensation for activities with GE Healthcare as a consultant. Dr. Beach has received research support from Avid Radiopharmaceuticals and GE Healthcare. Dr. Adler has received personal compensation for activities with Merz, Impax, Teva Neuroscience, and Novartis. Dr. Adler has received research support from Avid Radiopharmaceuticals. Dr. Shill has received research support from Schering-Plough/Merck, Avid Radiopharmaceuticals, UCB Biosciences, and Adamas Pharmaceuticals. Dr. Sue has nothing to disclose. Dr. Serrano has nothing to disclose. Dr. Dugger has nothing to disclose. Dr. Jacobson has received research support from Avid, Baxter, Bayer Pharmaceuticals Corporation, Bristol-Meyers Squibb Company, Celgene, Eisai Inc, Elan Corporation, Eli Lilly & Company, General Electric, Genentech Inc, Janssen Pharmaceutica, and Pfizer Inc. Dr. Sabbagh has received personal compensation for activities with Amerisciences, Pfizer Inc., Eisai Inc., Eli Lilly & Co., Avid Pharmaceuticals, Bristol-Myers Squibb Co., and Allon. Dr. Sabbagh has received royalty payments from Amerisciences and Wiley. Dr. Sabbagh has received research support from Avid, Baxter, Bayer Pharmaceuticals Inc., Bristol-Myers Squibb Co., Celgene, Eisai Inc., Elan Corp., Eli Lilly & Co., General Electric, Genentech Inc., Janssen/Wyeth Pharmaceuticals, and Pfizer Inc.