Unravelling the plasma proteome: Pioneering biomarkers for differential dementia diagnosis
Creators
- 1. Istanbul Univ Cerrahpasa, Inst Neurol Sci, Dept Neurosci, Brain & Neurodegenerat Disorders Res Labs, Istanbul, Turkiye
- 2. Istanbul Univ, Istanbul Fac Med, Dept Neurol, Behav Neurol & Movement Disorders Unit, Istanbul, Turkiye
- 3. UCL, Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London, England
- 4. Istanbul Univ, Aziz Sancar Inst Expt Med, Dept Genet, Istanbul, Turkiye
Description
INTRODUCTIONDiagnosing Alzheimer's disease (AD) is challenging due to overlapping symptoms with other dementias and the invasiveness of current biomarkers. This study introduces the NULISA platform, a novel proteomics technology, to evaluate diagnostic accuracy of known biomarkers and uncover novel biomarkers underlying different dementias.METHODSWe analyzed plasma and cerebrospinal fluid (CSF) samples from 248 participants diagnosed with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and mild cognitive impairment (MCI). Plasma biomarkers were evaluated using regression models, receiver operating characteristics curve (ROC) analysis, and pathway enrichment.RESULTSPlasma phosphorylated Tau217 (pTau217) demonstrated the highest diagnostic accuracy for AD, DLB, and FTD (area under the curve [AUCs]: 0.9, 0.84, and 0.79, respectively). CXCL1 (fractalkine), synaptosomal-associated protein 25 (SNAP25), triggering receptor expressed on myeloid cells 1 (TREM1), beta-synuclein, and tyrosine kinase (TEK) are expressed differently in DLB and FTD than AD. Ingenuity pathway analyses revealed astrocytic, synaptic, and inflammatory pathways as shared and distinct mechanisms across these dementia types.CONCLUSIONOur findings establish plasma pTau217 as a robust diagnostic marker. This study provides new plasma biomarkers for differential diagnosis of dementias with a noninvasive method.Highlights Plasma pTau217 showed high diagnostic accuracy for AD, DLB, and FTD. CXCL1, SNAP25, TREM1, beta-synuclein, and TEK are novel markers distinguishing other dementias from AD. Noninvasive plasma biomarkers enable diagnosis and differentiation of dementias.
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