Plasma p-tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease
Por:
Kac, PR, Alcolea, D, Montoliu-Gaya, L, Fernández, S, Rodriguez, JL, Maure, L, González-Ortiz, F, Benejam, B, Turton, M, Barroeta, I, Harrison, P, Videla, L, Ashton, NJ, Lleó, A, Zetterberg, H, Carmona-Iragui, M, Karikari, TK, Fortea, J, Blennow, K
Publicada:
1 abr 2025
Resumen:
BACKGROUNDAll individuals with Down syndrome (DS) will develop full-blown Alzheimers disease (AD) pathology by age 40. Several genes encoded in chromosome 21, including dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), have been proven to contribute to the pathology. Phosphorylation of tau at threonine-212 (p-tau212) is very sensitive to DYRK1A phosphorylation and is increased in DSAD brain lysates. Here, we assessed the potential of this biomarker in DSAD and sporadic AD.METHODSUsing single molecule array (Simoa) technology, we tested p-tau212 and p-tau181 (n = 245 for plasma, n = 114 matching cerebrospinal fluid [CSF] samples).RESULTSWe have confirmed that the levels of plasma p-tau212 are increased in the DS population and sporadic AD cases, including prodromal and mild cognitive impairment states. Plasma p-tau212 started increasing approximately when people became amyloid positron emission tomography positive.DISCUSSIONPlasma p-tau212 might have utility for theragnostics, monitoring therapy efficacy, and as a target engagement biomarker in clinical trials both in sporadic and DSAD.Highlights Plasma p-tau212 is increased in the Down syndrome (DS) population. Plasma p-tau212 increases approximate to 15 years before the disease onset in DSAD. Plasma p-tau212 accurately differentiates between control and disease groups. Plasma p-tau212 accurately differentiates amyloid beta (A beta)+ and A beta- participants.
Filiaciones:
Kac, PR:
Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Dept Psychiat & Neurochem, Goteborgsvagen31, S-43130 Molndal, Sweden
Alcolea, D:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBER, Ave Monforte de Lemos, Madrid, Spain
Montoliu-Gaya, L:
Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Dept Psychiat & Neurochem, Goteborgsvagen31, S-43130 Molndal, Sweden
Fernández, S:
Fundacio Catalana Sindrome, Barcelona Med Ctr, Carrer Comte Borrell, Barcelona, Spain
Rodriguez, JL:
Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Dept Psychiat & Neurochem, Goteborgsvagen31, S-43130 Molndal, Sweden
Maure, L:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBER, Ave Monforte de Lemos, Madrid, Spain
Fundacio Catalana Sindrome, Barcelona Med Ctr, Carrer Comte Borrell, Barcelona, Spain
González-Ortiz, F:
Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Dept Psychiat & Neurochem, Goteborgsvagen31, S-43130 Molndal, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Benejam, B:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit, Barcelona, Spain
Fundacio Catalana Sindrome, Barcelona Med Ctr, Carrer Comte Borrell, Barcelona, Spain
Turton, M:
Bioventix Plc, Farnham, England
Barroeta, I:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBER, Ave Monforte de Lemos, Madrid, Spain
Fundacio Catalana Sindrome, Barcelona Med Ctr, Carrer Comte Borrell, Barcelona, Spain
Harrison, P:
Bioventix Plc, Farnham, England
Videla, L:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBER, Ave Monforte de Lemos, Madrid, Spain
Fundacio Catalana Sindrome, Barcelona Med Ctr, Carrer Comte Borrell, Barcelona, Spain
Ashton, NJ:
Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Dept Psychiat & Neurochem, Goteborgsvagen31, S-43130 Molndal, Sweden
Stavanger Univ Hosp, Ctr Age Related Med, Stavanger, Norway
South London & Maudsley NHS Fdn, NIHR Biomed Res Ctr Mental Hlth, London, England
South London & Maudsley NHS Fdn, Biomed Res Unit Dementia, London, England
Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Old Age Psychiat, London, England
Lleó, A:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBER, Ave Monforte de Lemos, Madrid, Spain
Zetterberg, H:
Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Dept Psychiat & Neurochem, Goteborgsvagen31, S-43130 Molndal, Sweden
Fundacio Catalana Sindrome, Barcelona Med Ctr, Carrer Comte Borrell, Barcelona, Spain
Univ Wisconsin, Wisconsin Alzheimers Dis Res Ctr, Sch Med & Publ Hlth, Madison, WI USA
Hong Kong Ctr Neurodegenerat Dis, Clear Water Bay, Hong Kong, Peoples R China
UCL, UCL Queen Sq Inst Neurol, Dept Neurodegenerat Dis, London, England
UCL, UK Dementia Res Inst, London, England
Carmona-Iragui, M:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBER, Ave Monforte de Lemos, Madrid, Spain
Fundacio Catalana Sindrome, Barcelona Med Ctr, Carrer Comte Borrell, Barcelona, Spain
Karikari, TK:
Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Dept Psychiat & Neurochem, Goteborgsvagen31, S-43130 Molndal, Sweden
Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA
Fortea, J:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Biomed Res Inst St Pau, St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBER, Ave Monforte de Lemos, Madrid, Spain
Fundacio Catalana Sindrome, Barcelona Med Ctr, Carrer Comte Borrell, Barcelona, Spain
Blennow, K:
Univ Gothenburg, Inst Neurosci & Physiol, Sahlgrenska Acad, Dept Psychiat & Neurochem, Goteborgsvagen31, S-43130 Molndal, Sweden
Fundacio Catalana Sindrome, Barcelona Med Ctr, Carrer Comte Borrell, Barcelona, Spain
Sorbonne Univ, Pitie Salpetriere Hosp, Paris Brain Inst, ICM, Paris, France
Univ Sci & Technol China, Inst Aging & Brain Disorders, Neurodegenerat Disorder Res Ctr, Div Life Sci & Med, Hefei, Peoples R China
Univ Sci & Technol China, Inst Aging & Brain Disorders, Dept Neurol, Hefei, Peoples R China
USTC, Affiliated Hosp 1, Hefei, Peoples R China
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