Data_Sheet_1_Case report: Anti-ARHGAP26 autoantibodies in atypical dementia with Lewy bodies.pdf

BackgroundDementia with Lewy bodies (DLB) is the second most common type of neurodegenerative dementia. Here, we report a case of dementia associated with anti-Rho-GTPase-activating protein 26 (ARHGAP26) autoantibodies, which have never been previously linked to DLB.MethodsWe describe the case of a 78-year-old man who underwent cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), 18F-fluorodesoxyglucose positron emission tomography (FDG-PET), and a detailed neuropsychological evaluation.ResultsThe patient presented with mild dementia syndrome associated with extrapyramidal symptoms. Neuropsychological testing revealed impaired cognitive flexibility, figural memory, and verbal memory. Fluctuating cognitive abilities with deficits in attention-executive dysfunction and visuoconstruction also developed over time. A brain MRI showed reduced biparietal and cerebellar brain volume with generalized accentuation of the outer CSF spaces. The patient's CSF revealed anti-ARHGAP26 autoantibodies, which were also detectable in serum. In the differential complementary imaging diagnosis at 2 years, an FDG-PET revealed decreased occupancy of the posterior cingulum and precuneus. Although the FDG-PET, MRI, and clinical findings were potentially consistent with Alzheimer's disease, negative amyloid biomarkers in the CSF made an AD diagnosis highly unlikely. Single photon emission computed tomography (SPECT) with [(123)I] N-omega-fluoropropyl-2beta-carbomethoxy-3beta-{4-iodophenyl}nortropane ([(123)I]FP-CIT) showed right-sided predominance, reduced dopamine transporter uptake in the putamen, consistent with a positive indicative biomarker finding typical of DLB. Considering the clinically probable DLB associated with the two core features of Parkinsonism and fluctuating cognition with deficits in attention, supported by an abundant tracer uptake in the right putamen and lower uptake in the left putamen on 123I-FP-CIT-SPECT as an indicative biomarker, we started an antidementia drug using a cholinesterase inhibitor.ConclusionsOur report shows that atypical DLB may be associated with anti-ARHGAP26 autoantibodies, although their role and significance in the pathogenesis of DLB are unknown. However, it has to be mentioned that it is also possible that antibody-specific synthesis of anti-ARHGAP26 autoantibodies is a hallmark of a rare autoimmune disease that may cause the clinical and laboratory features involving altered dopamine transporter uptake on 123I-FP-CIT-SPECT, dementia, and mild Parkinson's symptoms rather than idiopathic DLB with only two core DLB features and inconsistent cognitive and imaging findings. Further research is needed to investigate the role of these autoantibodies in different dementias, particularly in DLB and mixed DLB-AD types.

背景莱维小体痴呆（DLB）是神经退行性痴呆的第二常见类型。本研究报告了一例与抗Rho-GTPase激活蛋白26（ARHGAP26）自身抗体相关的痴呆病例，该抗体此前从未与DLB相关联。方法：我们描述了一位78岁男性患者的病例，他接受了脑脊液（CSF）分析、磁共振成像（MRI）、18F-氟代脱氧葡萄糖正电子发射断层扫描（FDG-PET）以及详细的神经心理学评估。结果：患者表现出轻度痴呆综合征伴随锥体外系症状。神经心理学测试显示认知灵活性、图形记忆和言语记忆受损。随着时间的推移，认知能力波动，出现注意力-执行功能障碍和视觉构建能力下降。脑MRI显示双侧顶叶和脑干体积减少，脑脊液外空间普遍增大。患者的脑脊液检测到抗ARHGAP26自身抗体，这些抗体也可在血清中检测到。在2年时的鉴别诊断中，FDG-PET显示后扣带回和顶叶占位减少。尽管FDG-PET、MRI和临床发现与阿尔茨海默病（AD）相符，但脑脊液中的淀粉样蛋白生物标志物阴性，使得AD诊断极不可能。单光子发射计算机断层扫描（SPECT）[(123)I] N-omega-氟代丙基-2beta-羧甲基-3beta-{4-碘苯基}去甲托烷（[(123)I]FP-CIT）显示右侧优势，尾状核多巴胺转运蛋白摄取减少，这与DLB典型的阳性指示生物标志物发现一致。考虑到临床可能的DLB与帕金森病的两个核心特征以及注意力缺陷的认知波动相关，并且右尾状核的示踪剂摄取增加，左尾状核摄取减少，这些均支持123I-FP-CIT-SPECT作为指示生物标志物，我们开始使用胆碱酯酶抑制剂治疗痴呆。结论：我们的报告表明，非典型DLB可能与抗ARHGAP26自身抗体相关，尽管它们在DLB发病机制中的作用和意义尚不清楚。然而，必须指出的是，抗ARHGAP26自身抗体的抗体特异性合成也可能是罕见自身免疫病的特征，这种疾病可能导致涉及123I-FP-CIT-SPECT中多巴胺转运蛋白摄取改变、痴呆和轻度帕金森症状的临床和实验室特征，而不是仅具有两个核心DLB特征和认知及影像学发现不一致的特发性DLB。需要进一步研究这些自身抗体在痴呆不同类型中的作用，尤其是在DLB和DLB-AD混合类型中。