Background: With the introduction of disease-modifying treatments for Alzheimer’s disease (AD), less invasive and widely accessible screening tests are urgently needed. We assessed eight blood-based biomarkers in a well-defined cohort of preclinical AD, including participants with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Methods: Amyloid beta (Aβ) oligomerization tendency, Aβ42, Aβ40, Aβ42/Aβ40 ratio, phosphorylated tau (p-tau)181, p-tau217, glial fibrillary acidic protein (GFAP), and neurofilament light (Nf-L) were assessed for distinguishing between SCD and MCI, for correlations, and for predicting Aβ positron emission tomography (PET) positivity. Results: Plasma p-tau181, p-tau217, and GFAP levels were significantly higher in participants with MCI than in those with SCD (P < 0.05) and in Aβ PET-positive versus Aβ PET-negative participants (P < 0.0001), whereas plasma Aβ42 and Aβ42/40 ratio levels were significantly lower in Aβ PET-positive than in Aβ PET-negative participants (P < 0.001). Logistic regression analysis revealed that plasma Aβ42 and p-tau217 levels predicted Aβ PET positivity with an area under the ROC curve (AUC) of 0.930 (95% confidence interval [CI], 0.848–0.976) in the entire cohort, and p-tau217 alone predicted Aβ PET-positivity with an AUC of 0.887 (95% CI, 0.779–0.954) in the MCI subgroup. Conclusions Plasma p-tau217 levels outperform plasma p-tau181 levels in predicting Aβ PET-positivity in participants with preclinical AD. Plasma GFAP levels, along with different ptau isoforms (p-tau181 and p-tau217), effectively differentiate MCI from SCD. The predictive accuracy of blood-based biomarkers for Aβ PET-positivity strongly supports their clinical implementation, particularly with the introduction of disease-modifying therapies.

Objective: This study evaluated the pharmacokinetics and bioequivalence of eight oral IVM formulations (B–I) compared with the innovator product (A) in dogs. Methods: Forty-five healthy dogs (mean body weight: 14.3 kg) were divided into nine groups (n = 5). Each received 6.2 µg/kg of IVM orally. Blood samples were collected up to 72 h post-dosing, and plasma IVM concentrations were quantified by liquid chromatography– mass spectrometry. Pharmacokinetic parameters were analyzed using a one-compartment model. Bioequivalence was assessed non-compartmentally using 90% confidence intervals for maximum concentration (Cmax ) and area under the plasma concentration–time curve (AUC72h ), with acceptance limits of 80–125%. Results: Absorption (Ka = 0.09–0.16 h −1 ), elimination half-life (T1/2 = 4.89–14.97 h), and systemic exposure (Cmax = 6.07–7.59 ng/mL) varied among formulations. Formulation C showed prolonged elimination (14.97 h) and higher exposure (AUC72h = 214.16 ng·h/ mL), whereas formulation H exhibited faster absorption but lower exposure (AUC72h = 114.36 ng·h/mL). Simulated dosing indicated that most formulations maintained plasma levels above the minimum effective concentration (0.2 ng/mL), except formulation E. Only formulation G met full bioequivalence with the reference product. Conclusions and Relevance: All formulations achieved plasma concentrations sufficient for prophylaxis, but only B, C, and G satisfied bioequivalence criteria. Larger sample sizes and standardized evaluation guidelines are recommended for multi-formulation bioequivalence studies.