Beach Thomas G, Adler Charles H, Serrano Geidy, Sue Lucia I, Walker D G, Dugger Brittany N, Shill Holly A, Driver-Dunckley Erika, Caviness John N, Intorcia Anthony, Filon Jessica, Scott Sarah, Garcia Angelica, Hoffman Brittany, Belden Christine M, Davis Kathryn J, Sabbagh Marwan N
Banner Sun Health Research Institute, Sun City, AZ, USA.
Mayo Clinic, Scottsdale, AZ, USA.
J Parkinsons Dis. 2016;6(1):153-63. doi: 10.3233/JPD-150680.
Clinical misdiagnosis, particularly at early disease stages, is a roadblock to finding new therapies for Lewy body disorders. Biopsy of a peripheral site might provide improved diagnostic accuracy. Previously, we reported, from both autopsy and needle biopsy, a high prevalence of submandibular gland synucleinopathy in Parkinson's disease (PD). Here, we report on an extension of these studies to subjects with dementia with Lewy bodies (DLB) and other Lewy body disorders in 228 autopsied subjects from the Arizona Study of Aging and Neurodegenerative Disorders.
To provide an estimate of the prevalence of histological synucleinopathy in the submandibular glands of subjects with PD and other Lewy body disorders.
Submandibular gland sections from autopsied subjects were stained with an immunohistochemical method for α-synuclein phosphorylated at serine 129. Included were 146 cases with CNS Lewy-type synucleinopathy (LTS), composed of 46 PD, 28 DLB, 14 incidental Lewy body disease (ILBD), 33 Alzheimer's disease with Lewy bodies (ADLB) and 2 with progressive supranuclear palsy and Lewy bodies (PSPLB). Control subjects included 79 normal elderly, 15 AD, 12 PSP, 2 conticobasal degeneration (CBD) and 2 multiple system atrophy (MSA).
Submandibular gland LTS was found in 42/47 (89%) of the PD subjects, 20/28 (71%) DLB, 4/33 (12%) ADLB and 1/9 (11%) ILBD subjects but none of the 110 control subjects.
These results provide support for further clinical trials of in vivo submandibular gland diagnostic biopsy for PD and DLB. An accurate peripheral biopsy diagnosis would assist subject selection for clinical trials and could also be used to verify other biomarkers.
临床误诊,尤其是在疾病早期阶段,是为路易体疾病寻找新疗法的障碍。外周部位活检可能提高诊断准确性。此前,我们通过尸检和针吸活检报告了帕金森病(PD)患者下颌下腺突触核蛋白病的高患病率。在此,我们报告将这些研究扩展至来自亚利桑那衰老与神经退行性疾病研究的228例尸检受试者中的路易体痴呆(DLB)及其他路易体疾病患者。
估计PD及其他路易体疾病患者下颌下腺组织学突触核蛋白病的患病率。
对尸检受试者的下颌下腺切片进行免疫组织化学染色,检测丝氨酸129位点磷酸化的α-突触核蛋白。纳入146例中枢神经系统路易体样突触核蛋白病(LTS)患者,包括46例PD、28例DLB、14例路易体伴发疾病(ILBD)、33例路易体痴呆(ADLB)以及2例进行性核上性麻痹伴路易体(PSPLB)。对照受试者包括79例正常老年人、15例阿尔茨海默病(AD)、12例进行性核上性麻痹(PSP)、2例皮质基底节变性(CBD)和2例多系统萎缩(MSA)。
PD患者中42/47(89%)、DLB患者中20/28(71%)、ADLB患者中4/33(12%)以及ILBD患者中1/9(11%)存在下颌下腺LTS,而110例对照受试者均未发现。
这些结果为针对PD和DLB进行体内下颌下腺诊断性活检的进一步临床试验提供了支持。准确的外周活检诊断有助于临床试验的受试者选择,也可用于验证其他生物标志物。