Journal Article Ppublish
PubMed: 40613333 DOI: 10.1002/alz.70162
Unravelling the plasma proteome: Pioneering biomarkers for differential dementia diagnosis.
Alzheimers Dement 21(7):e70162
Authors: Haşim Gezegen, Merve Alaylıoğlu, Erdi Şahin, Owen Swann, Elena Veleva, Gamze Güven, Umran Yaman, Derviş A Salih, Başar Bilgiç, Haşmet Hanağası, Hakan Gürvit, Murat Emre, Duygu Gezen-Ak, Erdinç Dursun, Henrik Zetterberg, John Hardy, Amanda Heslegrave, Maryam Shoai, Bedia Samanci
Affiliations
- Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
- Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.
- Brain and Neurodegenerative Disorders Research Laboratories, Department of Neuroscience, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul, Turkey.
- Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.
- UK Dementia Research Institute at UCL, London, UK.
- Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK. UK Dementia Research Institute at UCL, London, UK. Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China. Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
- Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
Abstract
INTRODUCTION
Diagnosing 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.
METHODS
We 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.
RESULTS
Plasma 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), β-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.
CONCLUSION
Our 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, β-synuclein, and TEK are novel markers distinguishing other dementias from AD. Noninvasive plasma biomarkers enable diagnosis and differentiation of dementias.
MeSH
Dementia, Alzheimer Disease, Cognitive Dysfunction, Biomarkers, Diagnosis, Proteome, Synucleins, Roc Curve, Plasma
Cited by
- Unravelling the plasma proteome: Pioneering biomarkers for differential dementia diagnosis. Alzheimers Dement, 2025