Jordi A Matías-Guiu1, Ulises Gómez-Pinedo1, Lucía Forero2, Vanesa Pytel1, Fátima Cano3,4, Teresa Moreno-Ramos1, María Nieves Cabrera-Martín5, Jorge Matías-Guiu1, Javier J González-Rosa3,4. 1. Department of Neurology and Laboratory of Neurobiology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISCC), Universidad Complutense de Madrid, Madrid, Spain. 2. Department of Neurology, Puerta del Mar University Hospital, Cádiz, Spain. 3. Department of Psychology, Universidad de Cádiz, Cádiz, Spain. 4. Biomedical Research and Innovation Institute of Cádiz (INiBICA), Cádiz, Spain. 5. Department of Nuclear Medicine, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISCC), Universidad Complutense de Madrid, Madrid, Spain.
Abstract
BACKGROUND: Primary progressive aphasia (PPA) is a heterogeneous syndrome that is difficult to diagnose at early stages. Plasma neurofilament light chain (NFL) has been proposed as a potential biomarker for PPA. OBJECTIVE: To examine the diagnostic properties of plasma NFL in PPA and to evaluate its association with clinical stages of the disease and brain metabolism. METHODS: Our study included 80 participants (13 with non-fluent, 12 with semantic, and 16 with logopenic variant PPA; 13 with amnestic Alzheimer's disease [AD]; 13 with behavioral variant frontotemporal dementia; and 13 healthy controls). Plasma NFL concentration was measured using a high-sensitivity enzyme-linked immunosorbent assay (ELISA) kit. PET imaging was performed in a subgroup of patients. RESULTS: NFL discriminated patients from controls with an area under the curve of 0.914 (95% CI, 0.843-0.984; p < 0.001) (cut-off: 76.46 pg/mL; 94% sensitivity, 76.9% specificity). There were no significant differences between clinical syndromes (PPA subtypes), the main clinical forms of dementia (frontotemporal dementia and AD), or the expected pathological groups (frontotemporal lobar degeneration-tau [FTLD-tau], FTLD-TDP43, and AD). NFL levels showed weak to moderate correlations with age and functional scale score. We found no significant correlation with the extent of hypometabolism observed on FDG-PET images. CONCLUSION: Plasma NFL is a non-specific marker of neurodegeneration, and may be helpful in the diagnosis of PPA. However, NFL does not permit differential diagnosis between PPA subtypes and is not correlated with the extent of neurodegeneration.
BACKGROUND:Primary progressive aphasia (PPA) is a heterogeneous syndrome that is difficult to diagnose at early stages. Plasma neurofilament light chain (NFL) has been proposed as a potential biomarker for PPA. OBJECTIVE: To examine the diagnostic properties of plasma NFL in PPA and to evaluate its association with clinical stages of the disease and brain metabolism. METHODS: Our study included 80 participants (13 with non-fluent, 12 with semantic, and 16 with logopenic variant PPA; 13 with amnestic Alzheimer's disease [AD]; 13 with behavioral variant frontotemporal dementia; and 13 healthy controls). Plasma NFL concentration was measured using a high-sensitivity enzyme-linked immunosorbent assay (ELISA) kit. PET imaging was performed in a subgroup of patients. RESULTS:NFL discriminated patients from controls with an area under the curve of 0.914 (95% CI, 0.843-0.984; p < 0.001) (cut-off: 76.46 pg/mL; 94% sensitivity, 76.9% specificity). There were no significant differences between clinical syndromes (PPA subtypes), the main clinical forms of dementia (frontotemporal dementia and AD), or the expected pathological groups (frontotemporal lobar degeneration-tau [FTLD-tau], FTLD-TDP43, and AD). NFL levels showed weak to moderate correlations with age and functional scale score. We found no significant correlation with the extent of hypometabolism observed on FDG-PET images. CONCLUSION: Plasma NFL is a non-specific marker of neurodegeneration, and may be helpful in the diagnosis of PPA. However, NFL does not permit differential diagnosis between PPA subtypes and is not correlated with the extent of neurodegeneration.
Authors: Tania F Gendron; Michael G Heckman; Launia J White; Austin M Veire; Otto Pedraza; Alexander R Burch; Andrea C Bozoki; Bradford C Dickerson; Kimiko Domoto-Reilly; Tatiana Foroud; Leah K Forsberg; Douglas R Galasko; Nupur Ghoshal; Neill R Graff-Radford; Murray Grossman; Hilary W Heuer; Edward D Huey; Ging-Yuek R Hsiung; David J Irwin; Daniel I Kaufer; Gabriel C Leger; Irene Litvan; Joseph C Masdeu; Mario F Mendez; Chiadi U Onyike; Belen Pascual; Aaron Ritter; Erik D Roberson; Julio C Rojas; Maria Carmela Tartaglia; Zbigniew K Wszolek; Howard Rosen; Bradley F Boeve; Adam L Boxer; Leonard Petrucelli Journal: Cell Rep Med Date: 2022-04-19