| Contributors: |
Brembati, V.; Crescenti, D.; Geviti, A.; Rossini, E.; Cazzaniga, F. A.; Moda, F.; Zanier, E. R.; Guerrera, G.; Battistini, L.; Baiardi, S.; Mandelli, A.; Furlan, R.; Verde, F.; Nacmias, B.; Elia, C. A.; Malosio, M. L.; Imarisio, A.; Guerini, F. R.; Fenoglio, C.; Di Fonzo, A.; Biscetti, L.; Squillario, M.; Berra, S.; Miraglia, F.; Rossini, P. M.; Marra, C.; Vanacore, N.; Redolfi, A.; Perani, D.; Spadin, P.; Cotelli, M.; Cappa, S.; Caraglia, N.; Vecchio, F.; Tiraboschi, P.; Piras, F.; Frisoni, G. B.; Muscio, C.; Lodi, R.; Parchi, P.; Tagliavini, F.; Valente, E. M.; Forloni, G.; Ghidoni, R.; Parnetti, L.; Sorbi, S.; Bonanni, L.; Gerace, C.; Tedeschi, G.; Costa, A.; Sinforiani, E.; Capellari, S.; Pelliccioni, G.; Pardini, M.; Nobili, F. M.; Marcon, M.; Zanetti, O.; Ferrarese, C.; Rainero, I.; Lauretani, F.; Luzzi, S.; Gabelli, C.; Barbagallo, M.; Cassetta, E.; Quaranta, D.; Di Fede, G.; Catania, M.; Maderna, E.; Rossi, G.; Belfiglio, M.; Linarello, S.; Fiorani, A.; D'Alessandro, R.; Chiti, S.; Ginestroni, A.; Fainardi, E.; Passeri, A.; De Cristofaro, M. T.; Berti, V.; Pupi, A.; Lombardi, G.; Bagnoli, S.; Polito, C.; Floridi, P.; Chiarini, P.; Chiappiniello, A.; Tarducci, R.; Tranfaglia, C.; Dottorini, M. E.; Russo, M.; Farotti, L.; Montanucci, C.; Chipi, E.; Paghera, B.; Mascaro, L.; Corbo, D.; Gasparotti, R.; Rozzini, L.; Turrone, R.; Pelizzari, S. |
| Description: |
Background: Timely and accurate diagnosis of Alzheimer’s disease (AD) in clinical practice is a great challenge, especially during early disease stages with subtle or mild symptoms of cognitive decline. Moreover, robust and more accessible blood-based screening tests for early diagnosis are needed. In this study, we investigated the core AD blood biomarkers — amyloid beta 42 (Aβ42) and 40 (Aβ40) peptides, phosphorylated tau 181 (p-Tau181), neurofilament light chain (NfL), and total tau (t-Tau) — and extracellular vesicle (EVs) size and concentration in individuals characterized by different stages of cognitive decline to identify biochemical markers of dementia for early diagnosis. Methods: A total of n = 800 human plasma samples were analyzed. Plasma levels of NfL, t-Tau, p-Tau181, Aβ42, Aβ40 and plasma EVs were evaluated in n = 217 elderly healthy subjects (CTRL), in individuals with subjective cognitive complaints (SCC, n = 48), pre-mild cognitive impairment (pre-MCI, n = 58) and mild cognitive impairment (MCI, n = 426), and in n = 51 probable AD dementia patients (AD-dem), using ultrasensitive Single Molecule Array technology (Simoa®) and nanoparticle tracking analysis (NTA). Logistic regression and Receiver Operating Characteristic (ROC) analyses were employed. Results: Plasma NfL displayed increased levels in AD-dem and MCI patients, while p-Tau181, Aβ42/Aβ40 ratio, Aβ42/p-Tau181 ratio, and EVs plasma levels were altered since the early stages of the pathology: in particular, p-Tau181 levels increased as cognitive symptoms worsened, already in the SCC and pre-MCI groups compared to CTRL, while the ratio of EVs concentration and size (EVs ratio) was decreased in all groups compared to CTRL. Plasma p-Tau181 best classified AD-dem patients from CTRL with an area under the curve (AUC) equal to 0.87, while EVs ratio best differentiated SCC from CTRL (AUC = 0.78). Combining p-Tau181 and EVs ratio with Aβ42/Aβ40 ratio and NfL, respectively, significantly improved the classification of pre-MCI and MCI from CTRL ... |