Marcello Rossi1, Simone Baiardi1, Charlotte E Teunissen1, Corinne Quadalti1, Marleen van de Beek1, Angela Mammana1, Michelangelo Stanzani-Maserati1, Wiesje M Van der Flier1, Luisa Sambati1, Corrado Zenesini1, Byron Caughey1, Sabina Capellari1, Afina W Lemstra1, Piero Parchi2. 1. From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT. 2. From IRCCS (M.R., S.B., C.Q., A.M., M.S.-M., C.Z., S.C., P.P.), Istituto delle Scienze Neurologiche di Bologna; Department of Experimental, Diagnostic and Specialty Medicine (S.B., P.P.) and Department of Biomedical and Neuromotor Sciences (L.S., S.C.), University of Bologna, Italy; Neurochemistry Laboratory, Department of Clinical Chemistry (C.E.T.), and Department of Neurology (M.v.d.B., W.M.V.d.F., A.W.L.), Alzheimer Center Amsterdam, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and LPVD (B.C.), Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, MT. piero.parchi@unibo.it.
Abstract
OBJECTIVE: To investigate whether the CSF α-synuclein (α-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 α-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 α-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 α-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 α-syn RT-QuIC accurately identifies patients with MCI-LB. Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.
OBJECTIVE: To investigate whether the CSF α-synuclein (α-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 α-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 α-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 α-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 α-syn RT-QuIC accurately identifies patients with MCI-LB. Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.
Authors: Sara Hall; Christina D Orrù; Byron Caughey; Oskar Hansson; Geidy E Serrano; Douglas Galasko; Andrew G Hughson; Bradley R Groveman; Charles H Adler; Thomas G Beach Journal: Acta Neuropathol Commun Date: 2022-06-22 Impact factor: 7.578
Authors: Denis S Smirnov; Nicholas J Ashton; Kaj Blennow; Henrik Zetterberg; Joel Simrén; Juan Lantero-Rodriguez; Thomas K Karikari; Annie Hiniker; Robert A Rissman; David P Salmon; Douglas Galasko Journal: Acta Neuropathol Date: 2022-02-23 Impact factor: 15.887