Red blood cell α‐synuclein heteroaggregates can discriminate healthy controls from cognitively impaired subjects of the AD‐LBD spectrum: Biomarkers (non‐neuroimaging) / Novel biomarkers. (7th December 2020)

• Record Type: Journal Article
• Authors: Giampietri, Linda; Daniele, Simona; Piccarducci, Rebecca; Palermo, Giovanni; Manca, Maria Laura; Nicoletti, Valentina; Giorgi, Filippo Sean; Frosini, Daniela; Petrozzi, Lucia; Gerfo, Annalisa Lo; Pietrobono, Deborah; Cavallini, Chiara; Franzoni, Ferdinando; Trincavelli, Maria Letizia; Bonuccelli, Ubaldo; Siciliano, Gabriele; Tognoni, Gloria; Ceravolo, Roberto; Baldacci, Filippo; Martini, Claudia
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.040618
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: α‐synuclein's (α‐syn) pathological accumulation is involved in the development of Lewy body dementias (LBDs), namely Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). Several autoptic series have nonetheless documented pathologic α‐syn deposits up to 30% cases of otherwise confirmed Alzheimers's disease (AD) brains. A considerable body of evidence supports the mutual pathological interaction between α‐syn and AD's hallmark altered proteins, namely beta‐amyloid and tau, both in AD and LBDs. Aim of this study was to explore the diagnostic potential of red blood cells (RBCs) levels of α‐syn, beta‐amyloid 1‐42 (Aβ1‐42 ), total‐tau (t‐tau), and their heteromers in subjects with LBDs, AD, and healthy controls (HCs). Method: Total α‐syn, Aβ1‐42, t‐tau, α‐syn/Aβ1‐42, α‐syn/tau concentrations in RBCs were determined by means of an "in‐house" immunoenzimatic assay, and confronted in AD subjects (either AD Dementia or Prodromal‐AD, N=51), LDB subjects (either DLB or PDD, N=27), and HCs (N=60). Then, the diagnostic potential of each significant biomarker was examined calculating the area under the receiver operating characteristic curve (AUROC). Result: Compared to HCs, both AD and LBD subjects had significantly lower levels of t‐tau (4.25±4.99 and 3.19±5.13 ng/mg respectively, vs 8.43±11.52 ng/mg of HC) and α‐syn (16.46±15.85 and 15.31±18.30 ng/mg respectively, vs 39.62±57.19 ng/mg of HC) concentrations, as well α‐syn/tau heterodimers (1.04±1.54 and 0.86±0.10 ng/mg respectively, vs 2.36±1.87 ng/mg of HC), while only AD subjects showed significantly reduced levels of α‐syn/Aβ1‐42 (1.91±1.91 ng/mg vs 3.80±3.32 ng/mg in HC). Regarding t‐tau diagnostic accuracy, it turned out to be fair in differentiating LBD patients from HCs, and just poor in discriminating AD from HCs. Notably, RBCs α‐syn/tau heterodimers were able to discriminate LBD and AD subjects from HC with good and fair accuracy respectively. Similarly, α‐syn/Aβ1‐42 heterodimers concentrations were found to have fair accuracy in discriminating between AD and HCs (Table 1). Conclusion: RBC α‐syn heteromers concentrations were able to discriminate HCs from AD and LBD patients, though provided no help in the differential diagnosis of LBD vs AD. The interest for these data goes beyond eventual clinical implications, supporting new perspectives on the interaction of the different pathologies in these neurodegenerative diseases.