Current technological advancements in clinical and research settings have permitted a more intensive and comprehensive understanding of Alzheimer’s disease (AD). This development in knowledge regarding AD pathogenesis has been implemented to produce disease-modifying drugs. The potential for accessible and effective therapeutic methods has generated a need for detecting this neurodegenerative disorder during early stages of progression because such remedial effects are more profound when implemented during the initial, prolonged prodromal stages of pathogenesis. The aggregation of amyloid-β (Aβ) and tau isoforms are characteristic of AD; thus, they are considered core candidate biomarkers. However, research attempting to establish the reliability of Aβ and tau as biomarkers has culminated in an amalgamation of contradictory results and theories regarding the biomarker concentrations necessary for an accurate diagnosis. In this review, we consider the capabilities and limitations of fluid biomarkers collected from cerebrospinal fluid, blood, and oral, ocular, and olfactory secretions as diagnostic tools for AD, along with the impact of the integration of these biomarkers in clinical settings. Furthermore, the evolution of diagnostic criteria and novel research findings are discussed. This review is a summary and reflection of the ongoing concerted efforts to establish fluid biomarkers as a diagnostic tool and implement them in diagnostic procedures.
Amyloid‐β (Aβ) oligomers are implicated in Alzheimer disease (AD). However, their unstable nature and heterogeneous state disrupts elucidation of their explicit role in AD progression, impeding the development of tools targeting soluble Aβ oligomers. Herein parallel and anti‐parallel variants of Aβ(1–40) dimers were designed and synthesized, and their pathogenic properties in AD models characterized. Anti‐parallel dimers induced cognitive impairments with increased amyloidogenesis and cytotoxicity, and this dimer was then used in a screening platform. Through screening, two FDA‐approved drugs, Oxytetracycline and Sunitinib, were identified to dissociate Aβ oligomers and plaques to monomers in 5XFAD transgenic mice. In addition, fluorescent Astrophloxine was shown to detect aggregated Aβ in brain tissue and cerebrospinal fluid samples of AD mice. This screening platform provides a stable and homogeneous environment for observing Aβ interactions with dimer‐specific molecules.
Detection of amyloid-β (Aβ) aggregates contributes to the diagnosis of Alzheimer disease (AD). Plasma Aβ is deemed a less invasive and more accessible hallmark of AD, as Aβ can penetrate blood-brain barriers. However, correlations between biofluidic Aβ concentrations and AD progression has been tenuous. Here, we introduce a diagnostic technique that compares the heterogeneous and the monomerized states of Aβ in plasma. We used a small molecule, EPPS [4-(2-hydroxyethyl)-1-piperazinepropanesulfonic acid], to dissociate aggregated Aβ into monomers to enhance quantification accuracy. Subsequently, Aβ levels of EPPS-treated plasma were compared to those of untreated samples to minimize inter- and intraindividual variations. The interdigitated microelectrode sensor system was used to measure plasma Aβ levels on a scale of 0.1 pg/ml. The implementation of this self-standard blood test resulted in substantial distinctions between patients with AD and individuals with normal cognition (NC), with selectivity and sensitivity over 90%.
Methamphetamine can be peripherally sequestered through immunopharmacotherapy, in which advancements have been made regarding hapten chemistry, carrier proteins, and adjuvants.
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