Physiological Roles of Monomeric Amyloid-β and Implications for Alzheimer’s Disease Therapeutics

Alzheimer’s disease (AD) progressively inflicts impairment of synaptic functions with notable deposition of amyloid-β (Aβ) as senile plaques within the extracellular space of the brain. Accordingly, therapeutic directions for AD have focused on clearing Aβ plaques or preventing amyloidogenesis based on the amyloid cascade hypothesis. However, the emerging evidence suggests that Aβ serves biological roles, which include suppressing microbial infections, regulating synaptic plasticity, promoting recovery after brain injury, sealing leaks in the blood-brain barrier, and possibly inhibiting the proliferation of cancer cells. More importantly, these functions were found in in vitro and in vivo investigations in a hormetic manner, that is to be neuroprotective at low concentrations and pathological at high concentrations. We herein summarize the physiological roles of monomeric Aβ and current Aβ-directed therapies in clinical trials. Based on the evidence, we propose that novel therapeutics targeting Aβ should selectively target Aβ in neurotoxic forms such as oligomers while retaining monomeric Aβ in order to preserve the physiological functions of Aβ monomers.

Alzheimer's Disease Diagnosis Using Misfolding Proteins in Blood

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.

A Case of Recurrent Meningitis Caused by Rhodococcus species Successfully Treated with Antibiotic Treatment and Intrathecal Injection of Vancomycin through an Ommaya Reservoir

Human infection by Rhodococcus species is rare and mostly limited to immunocompromised hosts such as patients infected with the human immunodeficiency virus (HIV) or organ transplant recipients. The most common strain is R. equi, and the most common clinical presentation is pulmonary infection, reported in 80% of Rhodococcus spp. infections. The central nervous system is an uncommon infection site. We report a case of a patient with pneumonia, brain abscess, and recurrent meningitis caused by Rhodococcus spp. He initially presented with pneumonia with necrosis, which progressed to brain abscess and recurrent meningitis. Rhodococcus spp. was identified from the cerobrospinal fluid (CSF) collected during his fourth hospital admission. Despite prolonged treatment with appropriate antibiotics, meningitis recurred three times. Finally, in order to administer antibiotics directly into the CSF and bypass the blood-brain barrier, an Ommaya reservoir was inserted for administration of 90 days of intrathecal vancomycin and amikacin in conjunction with intravenous and oral antibiotics; the patient was finally cured with this treatment regimen.