Lipocalin-2 (LCN2) is an inflammatory protein with diverse functions in the brain. Although many studies have investigated the mechanism of LCN2 in brain injuries, the effect of LCN2 on amyloid-toxicity-related memory deficits in a mouse model of Alzheimer’s disease (AD) has been less studied. We investigated the role of LCN2 in human AD patients using a mouse model of AD. We created an AD mouse model by injecting amyloid-beta oligomer (AβO) into the hippocampus. In this model, animals exhibited impaired learning and memory. We found LCN2 upregulation in the human brain frontal lobe, as well as a positive correlation between white matter ischemic changes and serum LCN2. We also found increased astrocytic LCN2, microglia activation, iron accumulation, and blood–brain barrier disruption in AβO-treated hippocampi. These findings suggest that LCN2 is involved in a variety of amyloid toxicity mechanisms, especially neuroinflammation and oxidative stress.

Background/Aims: Disease-modifying therapy for Alzheimer’s disease (AD) has led to a need for biomarkers to identify prodromal AD and very early stage of AD dementia. We aimed to identify the cutoff values of cerebrospinal fluid (CSF) biomarkers for detecting prodromal AD. Methods: We assessed 56 patients with amnestic mild cognitive impairment (aMCI) who underwent lumbar puncture. Additionally, 87 healthy elderly individuals and 34 patients with AD dementia served as controls. Positron emission tomography was performed using florbetaben as a probe. We analyzed the concentration of Aβ_1–42, total tau protein (t-Tau), and tau protein phosphorylated at threonine 181 (p-Tau¹⁸¹) in CSF with INNOTEST enzyme-linked immunosorbent assay. Results: For the detection of prodromal AD in patients with aMCI, the cutoff values of CSF Aβ_1–42, t-Tau, and p-Tau¹⁸¹ were 749.5 pg/mL, 225.6 pg/mL, and 43.5 pg/mL, respectively. To discriminate prodromal AD in patients with aMCI, the t-Tau/Aβ_1–42 and ­p-Tau¹⁸¹/Aβ_1–42 ratios defined cutoff values at 0.298 and 0.059, respectively. Conclusions: CSF biomarkers are very useful tools for the differential diagnosis of prodromal AD in aMCI patients. The concentration of CSF biomarkers is well correlated with the stages of the AD spectrum.

Alzheimer’s disease (AD) is the most common form of dementia in the elderly population, but its underlying cause has not been fully elucidated. Recent studies have shown that microRNAs (miRNAs) play important roles in regulating the expression levels of genes associated with AD development. In this study, we analyzed miRNAs in plasma and cerebrospinal fluid (CSF) from AD patients and cognitively normal (including amyloid positive) individuals. miR-1273g-3p was identified as an AD-associated miRNA and found to be elevated in the CSF of early-stage AD patients. The overexpression of miR-1273g-3p enhanced amyloid beta (Aβ) production by inducing oxidative stress and mitochondrial impairments in AD model cell lines. A biotin-streptavidin pull-down assay demonstrated that miR-1273g-3p primarily interacts with mitochondrial genes, and that their expression is downregulated by miR-1273g-3p. In particular, the miR-1273g-3p-target gene TIMM13 showed reduced expression in brain tissues from human AD patients. These results suggest that miR-1273g-3p expression in an early stage of AD notably contributes to Aβ production and mitochondrial impairments. Thus, miR-1273g-3p might be a biomarker for early diagnosis of AD and a potential therapeutic target to prevent AD progression.

Food Science of Animal Resources (Food Sci. Anim. Resour.) is an international, peer-reviewed bimonthly journal publishing original research and reviews on basic and applied aspects of the use of animal resources including the meat, egg, dairy, and edible insect/worm products. Food Sci. Anim. Resour. is published and distributed by the Korean Society for Food Science of Animal Resources.

The gut–brain axis (GBA) plays a significant role in various neurodegenerative disorders, such as Alzheimer’s disease (AD), and the gut microbiome (GM) can bidirectionally communicate with the brain through the GBA. Thus, recent evidence indicates that the GM may affect the pathological features and the progression of AD in humans. The aim of our study was to elucidate the impact of probiotics on the pathological features of AD in a 5xFAD model. Probiotics (Bifidobacterium lactis, Levilactobacillus brevis, and Limosilactobacillus fermentum) were orally administered in 5xFAD mice to modify the GM composition. Additionally, freeze-dried food containing phosphatidylserine was used as the positive control. Behavioral pathogenesis was assessed through the cross maze and Morris water maze tests. Our findings revealed that probiotic administration resulted in significant improvements in spatial and recognition memories. Furthermore, the neuroprotective effects of probiotics were substantiated by a reduction in amyloid-β accumulation in critical brain regions. Microglial activation in 5xFAD mice was also attenuated by probiotics in the hippocampus and cerebral cortex. Moreover, elevated tau phosphorylation in 5xFAD mice was ameliorated in the probiotics-treated group. The results highlight the potential use of probiotics as a neuroprotective intervention in AD.

Background: Alzheimer’s disease (AD) is the most common cause of dementia and most of AD patients suffer from vascular abnormalities and neuroinflammation. There is an urgent need to develop novel blood biomarkers capable of diagnosing Alzheimer’s disease (AD) at very early stage. This study was performed to find out new accurate plasma diagnostic biomarkers for AD by investigating a direct relationship between plasma contact system and AD. Methods: A total 101 of human CSF and plasma samples from normal and AD patients were analyzed. The contact factor activities in plasma were measured with the corresponding specific peptide substrates. Results: The activities of contact factors (FXIIa, FXIa, plasma kallikrein) and FXa clearly increased and statistically correlated as AD progresses. We present here, for the first time, the FXIIa cut-off scores to as: > 26.3 U/ml for prodromal AD [area under the curve (AUC) = 0.783, p < 0.001] and > 27.2 U/ml for AD dementia (AUC = 0.906, p < 0.001). We also describe the cut-off scores from the ratios of CSF Aβ_1–42 versus the contact factors. Of these, the representative ratio cut-off scores of Aβ_1–42/FXIIa were to be: < 33.8 for prodromal AD (AUC = 0.965, p < 0.001) and < 27.44 for AD dementia (AUC = 1.0, p < 0.001). Conclusion: The activation of plasma contact system is closely associated with clinical stage of AD, and FXIIa activity as well as the cut-off scores of CSF Aβ_1–42/FXIIa can be used as novel accurate diagnostic AD biomarkers.