Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer's disease
Por:
Ewers, M, Franzmeier, N, Suarez-Calvet, M, Morenas-Rodriguez, E, Caballero, MAA, Kleinberger, G, Piccio, L, Cruchaga, C, Deming, Y, Dichgans, M, Trojanowski, JQ, Shaw, LM, Weiner, MW, Haass, C, Alzheimers Dis Neuroimaging Initia
Publicada:
28 ago 2019
Resumen:
Loss of function of TREM2, a key receptor selectively expressed by microglia in the brain, contributes to the development of Alzheimer's disease (AD). We therefore examined whether soluble TREM2 (sTREM2) concentrations in cerebrospinal fluid (CSF) were associated with reduced rates of cognitive decline and clinical progression in subjects with AD or mild cognitive impairment (MCI). We measured sTREM2 in CSF samples from 385 elderly subjects, including cognitively normal controls, individuals with MCI, and subjects with AD dementia (follow-up period: mean, 4 years; range 1.5 to 11.5 years). In subjects with AD defined by evidence of CSF A beta(1-42) (amyloid beta-peptide 1 to 42; A+) and CSF p-tau(181) (tau phosphorylated on amino acid residue 181; T+), higher sTREM2 concentrations in CSF at baseline were associated with attenuated decline in memory and cognition. When analyzed in clinical subgroups, an association between higher CSF sTREM2 concentrations and subsequent reduced memory decline was consistently observed in individuals with MCI or AD dementia, who were positive for CSF A beta(1-42) and CSF p-tau(181) (A+T+). Regarding clinical progression, a higher ratio of CSF sTREM2 to CSF p-tau(181) concentrations predicted slower conversion from cognitively normal to symptomatic stages or from MCI to AD dementia in the subjects who were positive for CSF A beta(1-42) and CSF p-tau(181). These results suggest that sTREM2 is associated with attenuated cognitive and clinical decline, a finding with important implications for future clinical trials targeting the innate immune response in AD.
Filiaciones:
Ewers, M:
LMU, Univ Hosp Munich, Inst Stroke & Dementia Res, Munich, Germany
Franzmeier, N:
LMU, Univ Hosp Munich, Inst Stroke & Dementia Res, Munich, Germany
Suarez-Calvet, M:
Ludwig Maximilians Univ Munchen, Fac Med, Biomed Ctr BMC, Chair Metab Biochem, Munich, Germany
German Ctr Neurodegenerat Dis DZNE Munich, Munich, Germany
Pasqua Maragall Fdn, Barcelonabeta Brain Res Ctr, Barcelona, Catalonia, Spain
Hosp del Mar, Dept Neurol, Barcelona, Catalonia, Spain
Morenas-Rodriguez, E:
Ludwig Maximilians Univ Munchen, Fac Med, Biomed Ctr BMC, Chair Metab Biochem, Munich, Germany
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Inst Invest Biomed, Dept Neurol, Barcelona, Spain
Caballero, MAA:
LMU, Univ Hosp Munich, Inst Stroke & Dementia Res, Munich, Germany
Kleinberger, G:
Ludwig Maximilians Univ Munchen, Fac Med, Biomed Ctr BMC, Chair Metab Biochem, Munich, Germany
Munich Cluster Syst Neurol SyNergy, Munich, Germany
ISAR Biosci GmbH, D-82152 Planegg, Germany
Piccio, L:
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
Washington Univ, Hope Ctr Neurol Disorders, Sch Med, St Louis, MO USA
Univ Sydney, Brain & Mind Ctr, Sydney, NSW, Australia
Cruchaga, C:
Washington Univ, Hope Ctr Neurol Disorders, Sch Med, St Louis, MO USA
Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA
Deming, Y:
Washington Univ, Hope Ctr Neurol Disorders, Sch Med, St Louis, MO USA
Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA
Dichgans, M:
LMU, Univ Hosp Munich, Inst Stroke & Dementia Res, Munich, Germany
German Ctr Neurodegenerat Dis DZNE Munich, Munich, Germany
Munich Cluster Syst Neurol SyNergy, Munich, Germany
Trojanowski, JQ:
Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA
Shaw, LM:
Univ Penn, Perelman Sch Med, Inst Aging, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA
Weiner, MW:
Univ Calif San Francisco, San Francisco, CA 94143 USA
Haass, C:
Ludwig Maximilians Univ Munchen, Fac Med, Biomed Ctr BMC, Chair Metab Biochem, Munich, Germany
German Ctr Neurodegenerat Dis DZNE Munich, Munich, Germany
Munich Cluster Syst Neurol SyNergy, Munich, Germany
Green Accepted, Bronze
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