Alzheimer's disease (AD) is pathologically characterized by a long progressive phase of neuronal changes, including accumulation of extracellular amyloid-β (Aβ) and intracellular neurofibrillary tangles, before the onset of observable symptoms. Many efforts have been made to develop a blood-based diagnostic method for AD by incorporating Aβ and tau as plasma biomarkers. As blood tests have the advantages of being highly accessible and low cost, clinical implementation of AD blood tests would provide preventative screening to presymptomatic individuals, facilitating early identification of AD patients and, thus, treatment development in clinical research. However, the low concentration of AD biomarkers in the plasma has posed difficulties for accurate detection, hindering the development of a reliable blood test. In this review, we introduce three AD blood test technologies emerging in South Korea, which have distinctive methods of heightening detection sensitivity of specific plasma biomarkers. We discuss in detail the multimer detection system, the self-standard analysis of Aβ biomarkers quantified by interdigitated microelectrodes, and a biomarker ratio analysis comprising Aβ and tau.

Pyroglutamate amyloid-β3-42 (AβpE3-42) is an N-terminally truncated and pyroglutamate-modified Aβ peptide retaining highly hydrophobic, amyloidogenic, and neurotoxic properties. In Alzheimer’s disease (AD) patients, AβpE3-42 peptides accumulate into oligomers and induce cellular toxicity and synaptic dysfunction. AβpE3-42 aggregates further seed the formation of amyloid plaques, which are the pathological hallmarks of AD. Given that AβpE3-42 peptides play critical roles in the development of neurodegeneration, a reliable and reproducible synthetic access to these peptides may support pathological and medicinal studies of AD. Here, we synthesized AβpE3-42 peptides through the microwave-assisted solid-phase peptide synthesis (SPPS). Utilizing thioflavin T fluorescence assay and dot blotting analysis with anti-amyloid oligomer antibody, the amyloidogenic activity of synthesized AβpE3-42 peptides was confirmed. We further observed the cytotoxicity of AβpE3-42 aggregates in cell viability test. To examine the cognitive deficits induced by synthetic AβpE3-42 peptides, AβpE3-42 oligomers were intracerebroventricularly injected into imprinting control region mice and Y-maze and Morris water maze tests were performed. We found that AβpE3-42 aggregates altered the expression level of postsynaptic density protein 95 in cortical lysates. Collectively, we produced AβpE3-42 peptides in the microwave-assisted SPPS and evaluated the amyloidogenic and pathological function of the synthesized peptides.

Amyloid-β (Aβ) in the form of neurotoxic aggregates is regarded as the main pathological initiator and key therapeutic target of Alzheimer's disease. However, anti-Aβ drug development has been impeded by the lack of a target needed for structure-based drug design and low permeability of the blood-brain barrier (BBB). An attractive therapeutic strategy is the development of amyloid-based anti-Aβ peptidomimetics that exploit the self-assembling nature of Aβ and penetrate the BBB. Herein, we designed a dimeric peptide drug candidate based on the N-terminal fragment of Aβ, DAB, found to cross the BBB and solubilize Aβ oligomers and fibrils. Administration of DAB reduced amyloid burden in 5XFAD mice, and downregulated neuroinflammation and prevented memory impairment in the Y-maze test. Peptide mapping assays and molecular docking studies were utilized to elucidate DAB-Aβ interaction. To further understand the active regions of DAB, we assessed the dissociative activity of DAB with sequence modifications.

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Amyloid-β (Aβ) in the form of neurotoxic aggregates is regarded as the main pathological initiator and key therapeutic target of Alzheimer's disease. However, anti-Aβ drug development has been impeded by the lack of a target needed for structure-based drug design and low permeability of the blood-brain barrier (BBB). An attractive therapeutic strategy is the development of amyloid-based anti-Aβ peptidomimetics that exploit the self-assembling nature of Aβ and penetrate the BBB. Herein, we designed a dimeric peptide drug candidate based on the N-terminal fragment of Aβ, DAB, found to cross the BBB and solubilize Aβ oligomers and fibrils. Administration of DAB reduced amyloid burden in 5XFAD mice, and downregulated neuroinflammation and prevented memory impairment in the Y-maze test. Peptide mapping assays and molecular docking studies were utilized to elucidate DAB-Aβ interaction. To further understand the active regions of DAB, we assessed the dissociative activity of DAB with sequence modifications.