Differential levels of plasma biomarkers of neurodegeneration in Lewy body dementia, Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy
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Differential levels of plasma biomarkers of neurodegeneration in Lewy body dementia, Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy. / Chouliaras, Leonidas; Thomas, Alan; Malpetti, Maura; Donaghy, Paul; Kane, Joseph; Mak, Elijah; Savulich, George; Prats-Sedano, Maria A.; Heslegrave, Amanda J.; Zetterberg, Henrik; Su, Li; Rowe, James Benedict; O'Brien, John Tiernan.
I: Journal of neurology, neurosurgery, and psychiatry, Bind 93, Nr. 6, 2022, s. 651-658.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Differential levels of plasma biomarkers of neurodegeneration in Lewy body dementia, Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy
AU - Chouliaras, Leonidas
AU - Thomas, Alan
AU - Malpetti, Maura
AU - Donaghy, Paul
AU - Kane, Joseph
AU - Mak, Elijah
AU - Savulich, George
AU - Prats-Sedano, Maria A.
AU - Heslegrave, Amanda J.
AU - Zetterberg, Henrik
AU - Su, Li
AU - Rowe, James Benedict
AU - O'Brien, John Tiernan
N1 - Publisher Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
PY - 2022
Y1 - 2022
N2 - OBJECTIVES: This longitudinal study compared emerging plasma biomarkers for neurodegenerative disease between controls, patients with Alzheimer's disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP). METHODS: Plasma phosphorylated tau at threonine-181 (p-tau181), amyloid beta (Αβ)42, Aβ40, neurofilament light (NfL) and glial fibrillar acidic protein (GFAP) were measured using highly sensitive single molecule immunoassays (Simoa) in a multicentre cohort of 300 participants (controls=73, amyloid positive mild cognitive impairment (MCI+) and AD dementia=63, LBD=117, FTD=28, PSP=19). LBD participants had known positron emission tomography (PET)-Aβ status. RESULTS: P-tau181 was elevated in MCI+AD compared with all other groups. Aβ42/40 was lower in MCI+AD compared with controls and FTD. NfL was elevated in all dementias compared with controls while GFAP was elevated in MCI+AD and LBD. Plasma biomarkers could classify between MCI+AD and controls, FTD and PSP with high accuracy but showed limited ability in differentiating MCI+AD from LBD. No differences were detected in the levels of plasma biomarkers when comparing PET-Aβ positive and negative LBD. P-tau181, NfL and GFAP were associated with baseline and longitudinal cognitive decline in a disease specific pattern. CONCLUSION: This large study shows the role of plasma biomarkers in differentiating patients with different dementias, and at monitoring longitudinal change. We confirm that p-tau181 is elevated in MCI+AD, versus controls, FTD and PSP, but is less accurate in the classification between MCI+AD and LBD or detecting amyloid brain pathology in LBD. NfL was elevated in all dementia groups, while GFAP was elevated in MCI+AD and LBD.
AB - OBJECTIVES: This longitudinal study compared emerging plasma biomarkers for neurodegenerative disease between controls, patients with Alzheimer's disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP). METHODS: Plasma phosphorylated tau at threonine-181 (p-tau181), amyloid beta (Αβ)42, Aβ40, neurofilament light (NfL) and glial fibrillar acidic protein (GFAP) were measured using highly sensitive single molecule immunoassays (Simoa) in a multicentre cohort of 300 participants (controls=73, amyloid positive mild cognitive impairment (MCI+) and AD dementia=63, LBD=117, FTD=28, PSP=19). LBD participants had known positron emission tomography (PET)-Aβ status. RESULTS: P-tau181 was elevated in MCI+AD compared with all other groups. Aβ42/40 was lower in MCI+AD compared with controls and FTD. NfL was elevated in all dementias compared with controls while GFAP was elevated in MCI+AD and LBD. Plasma biomarkers could classify between MCI+AD and controls, FTD and PSP with high accuracy but showed limited ability in differentiating MCI+AD from LBD. No differences were detected in the levels of plasma biomarkers when comparing PET-Aβ positive and negative LBD. P-tau181, NfL and GFAP were associated with baseline and longitudinal cognitive decline in a disease specific pattern. CONCLUSION: This large study shows the role of plasma biomarkers in differentiating patients with different dementias, and at monitoring longitudinal change. We confirm that p-tau181 is elevated in MCI+AD, versus controls, FTD and PSP, but is less accurate in the classification between MCI+AD and LBD or detecting amyloid brain pathology in LBD. NfL was elevated in all dementia groups, while GFAP was elevated in MCI+AD and LBD.
KW - alzheimer's disease
KW - dementia
KW - frontotemporal dementia
KW - lewy body dementia
KW - movement disorders
U2 - 10.1136/jnnp-2021-327788
DO - 10.1136/jnnp-2021-327788
M3 - Journal article
C2 - 35078917
AN - SCOPUS:85124301289
VL - 93
SP - 651
EP - 658
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
SN - 0022-3050
IS - 6
ER -
ID: 320677174