Diagnostic Value of the CSF α-Synuclein Real-Time Quaking-Induced Conversion Assay at the Prodromal MCI Stage of Dementia With Lewy Bodies

被引:57
作者
Rossi, Marcello [1 ]
Baiardi, Simone [1 ,2 ]
Teunissen, Charlotte E. [4 ]
Quadalti, Corinne [1 ]
van de Beek, Marleen [5 ]
Mammana, Angela [1 ]
Stanzani-Maserati, Michelangelo [1 ]
van der Flier, Wiesje M. [5 ]
Sambati, Luisa [3 ]
Zenesini, Corrado [1 ]
Caughey, Byron [6 ,7 ]
Capellari, Sabina [1 ,3 ]
Lemstra, Afina W. [5 ]
Parchi, Piero [1 ,2 ]
机构
[1] Univ Bologna, IRCCS, Ist Sci Neurologiche Bologna, Bologna, Italy
[2] Univ Bologna, Dept Expt Diagnost & Specialty Med, Bologna, Italy
[3] Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy
[4] Vrije Univ Amsterdam, Neurochem Lab, Dept Clin Chem, Amsterdam, Netherlands
[5] Vrije Univ Amsterdam, Amsterdam UMC, Alzheimer Ctr Amsterdam, Amsterdam Neurosci,Dept Neurol, Amsterdam, Netherlands
[6] Vrije Univ Amsterdam, LPVD, Amsterdam, Netherlands
[7] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA
关键词
ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; CRITERIA; PROTEIN;
D O I
10.1212/WNL.0000000000012438
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective To investigate whether the CSF alpha-synuclein (alpha-syn) real-time quaking-induced conversion (RT-QuIC) assay accurately identifies patients with mild cognitive impairment (MCI) due to probable Lewy body (LB) disease. Methods We applied alpha-syn RT-QuIC to 289 CSF samples obtained from 2 independent cohorts, including 81 patients with probable MCI-LB (age 70.7 +/- 6.6 years, 13.6% female, Mini-Mental State Examination [MMSE] score 26.1 +/- 2.4), 120 with probable MCI due to Alzheimer disease (AD) (age 68.6 +/- 7.4 years, 45.8% female, MMSE score 25.5 +/- 2.8), and 30 with unspecified MCI (age 65.4 +/- 9.3 years, 30.0% female, MMSE score 27.0 +/- 3.0). Fifty-eight individuals with no cognitive decline or evidence of neurodegenerative disease and 121 individuals lacking brain alpha-syn deposits at the neuropathologic examination were used as controls. Results RT-QuIC identified patients with MCI-LB against cognitively unimpaired controls with 95% sensitivity, 97% specificity, and 96% accuracy and showed 98% specificity in neuropathologic controls. The accuracy of the test for MCI-LB was consistent between the 2 cohorts (97.3% vs 93.7%). Thirteen percent of patients with MCI-AD also had a positive test; of note, 44% of them developed 1 core or supportive clinical feature of dementia with Lewy bodies (DLB) at follow-up, suggesting an underlying LB copathology. Conclusions These findings indicate that CSF alpha-syn RT-QuIC is a robust biomarker for prodromal DLB. Further studies are needed to fully explore the added value of the assay to the current research criteria for MCI-LB. Classification of Evidence This study provides Class III evidence that CSF alpha-syn RT-QuIC accurately identifies patients with MCI-LB.
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收藏
页码:E930 / E940
页数:11
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