Amyloid-β

…Recently, Amyloid-β (Aβ) plaques (APs) and phosphorylated tau (ptau) changes in neurons and neuropil were observed in different mammal species, with very few descriptions in cetaceans. This study describes Aβ deposition in the brain tissue of a female striped dolphin (Stenella coeruleoalba) stranded in the Ligurian coast of the

…(PS) 1 and 2, which are pivotal in amyloid-β (Aβ) production and amyloid pathology. PS functions, associated with inherited AD (FAD), extend beyond Aβ production. PS2 in particular is critical in mitochondrial function and cell bioenergetics. Here, we aim to explore Presenilins' role in cellular lipid metabolism.Brain samples were collected from WT, PS2 +/-, PS2 -/- and PS2N141I mice, carrying the FAD N141I mutation. We evaluated LPL and nSMase 2 levels based on preliminary data indicating their upregula

Alzheimer's disease (AD) is one of the most significant neurodegenerative diseases, and its effective treatment remains a challenge. Dehydroepiandrosterone (DHEA) is an androgen molecule, which in vitro protects against amyloid-ß (Aß) toxicity, and so might potentially improve cognitive functions. As steroid might influence wide range of processes both short (via membrane receptors) and long term (via intracellular receptors) we can expect beneficial effect already after one injection.Six months old male 3xTg-AD mice were treated intraperitoneally with DHEAS (a water-soluble sulphate salt of D

…of extracellular plaques of aggregated amyloid-β (Aβ) peptide, neurofibrillary tangles composed of truncated and hyperphosphorylated Tau protein, both leading to synaptic loss, and neuronal death. To ensure cerebral homeostasis, several elimination mechanisms exist for these toxic proteins. Recently, a complex mechanism based on exchanges between different extracellular space has been identified in the brain: the glymphatic system. Our aim is to study how the brain-gut axis participates

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by Amyloid β (Aβ)-driven synaptic dysfunction in the early phases of pathogenesis. However, cytoskeletal abnormalities, such as cofilin-actin rods, have been described in AD patients. In addition, we demonstrated that the actin-binding protein Cyclase-associated protein 2 (CAP2) is a master regulator of cofilin synaptic localization through the Cys32-dependent CAP2 dimerization. The CAP2 dimer-mediated cofilin translocation is required for synaptic plasticity-driven spine remodelling.This mechanism is altered in AD since CA

Alzheimer's disease is the most prevalent form of dementia in elderly, presenting a significant global public health challenge. Its pathological hallmarks include extracellular amyloid β (Aβ) aggregates or senile plaques, intracellular neurofibrillary tangles, and inflammatory processes. Despite recent therapeutic approvals targeting Aβ, controversies persist regarding their efficacy. Our goal is to determine the biological impact of molecules that inhibit various steps of Alzheimer's development, which could potentially be integrated into complex treatment regimens in the future. To this end,

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder associated with memory and cognitive deficits. Both amyloid β (Aβ) deposition and inflammatory response occur in the early course of AD, but the progression of cognitive impairment and its relationship with Aβ and neuroinflammation have not been fully understood. Dieckol is a phenolic compound from brown algae and has been reported to possess several health benefits. In particular, our previous studies have shown that the compound exerts the neuroprotective effects by inhibiting amyloidogenesis, oxidative stress and inflamma

…Aims: to explore the impact of amyloid-β (Aβ) pathology on the nanoscale compartmentalization of CaV2.1-GABAB in the hippocampus.Methods: We used histoblot and SDS-digested freeze-fracture replica labelling (SDS-FRL) techniques in the CA1 field of the hippocampus

A growing body of evidence indicates a substantial role of the immune system and inflammation in the pathogenesis of Alzheimer’s disease (AD). In the current study, we investigated the effect of maternal immune activation (MIA) on AD-resembling pathological alterations in 12-month-old offspring. We also aimed to analyze whether inhibition of bromodomain and extraterminal domain (BET) proteins, the readers of the histone acetylation code, might impact these changes. In our study, we injected a viral mimetic polyinosinic-polycytidylic acid (PIC) at gestation day 17 to evoke MIA in wild-type mice

…in Alzheimer’s disease (AD), and amyloid-β (Aβ) can activate AMPK

…anoxia [1] and express high levels of amyloid-β without developing amyloid plaques [2]. Our aim is to understand if altered lipid metabolism through regulation of lipid droplets (LDs) in brain cells is one of the NMRs intrinsic adaptations, giving them their long-lived phenotype and resistance to neurological damage. Immunohistochemistry was performed on bra

Background: Ginseng is a representative functional food for brain health. However, its active ingredient is not well defined. Gintonin is a novel material isolated from white/red ginseng and its lysophosphatidic acid (LPA) plays as an exogenous G protein-coupled LPA receptor (LPAR) agonist. Korean red ginseng marc (KRGM) is a by-product after KRG extractions. Purpose: In previous study, we demonstrated that KRGM-derived gintonin (KRGM-G) contains LPA C18:2, which is a major functional component, as much as white and/or red ginseng has. Methods: In present study, we further studied KRGM-G-media

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) and tau neuropathology, neuroinflammation, lipid dysregulation, and progressive loss of cognitive functioning. We have evidence that early dietary interventions with ω6/ω3 polyunsaturated fatty acids (PUFAs) can protect against cognitive decline and lastingly alter microglia and brain lipid profile in the context of early-life stress​. PUFAs can directly modulate microglia. In the context of AD, it is unknown if lipid and PUFA derivatives (oxylipins) are dysregulated in the brain, how these rel

Obesity and excessive consumption of saturated fats represent important predisposing factors to the development of neurodegenerative disorders such as Alzheimer's disease (AD) and its neuropsychiatric comorbidities. Alteration of amyloid β (Aβ) homeostasis is considered the main neuropathological feature of AD and increased levels of the oligomeric forms of this peptide have been associated with increased risk of depressive states. The exposure to obesogenic environment, such as high fat diet (HFD), seems to impair Aβ catabolic function leading to the production of its neurotoxic species. In t

…neurodegenerative disorder marked by amyloid-β accumulation, tauopathy, neuroinflammation, and cognitive decline. Parallel to this cognitive decline, the number of memory-related neurons (engram cells) is reduced in the APPswe/PSEN1dE9 mouse model for slow-progressing AD, crossed with a genetically modified mouse line that allows us to visualize engram neurons (Arc::dVenus mice). We hypothesize that aberrant microglial modulation of engram cells might contribute to the AD-related changes in engram and co

Lewy body diseases (LBD) are complex neurodegenerative conditions that originate from an accumulation of misfolded alpha-synuclein (α-syn) often association with other proteins such as Amyloid β (Aβ), Tau, and TAR-DNA-binding protein. However, the nature of this association is poorly understood. To investigate the complex pathology of LBD, we constructed 2 novel transgenic overexpressing C. elegans models using human genes (α-synA53T;Taupro-agg and α-synA53T;Aβ1-42;Taupro-agg ). We then investigated the molecular, physiologic, and behavioral alterations of these and previously produced models.

The deposition of amyloid-β (Aβ) peptides has been implicated as a one of pathological hallmark of Alzheimer's disease (AD). Increasing evidence indicates that Aβ initiates oxidative stress and a vicious cycle of mitochondrial damage, leading to apoptotic neuronal death. Pinocembrin (5,7-dihydroxyflavone), a major flavonoid found in honey and propolis, has shown significant neuroprotective property by suppressing Aβ cleaving enzyme in our previous study. The present study investigated a novel anti-AD effect of pinocembrin on mitochondrial dysfunction and apoptosis against Aβ injury. Neurotoxic

…Ensheathing Cells (OECs) exposed to amyloid-β (Aβ). In addition, we investigated on tissue tr

Aging is the main risk factor for Alzheimer’s disease (AD), a prevalent and devastating neurodegenerative pathology with no effective cure. Research efforts aimed at understanding the link between pathological aging (senescence) and AD are crucial for developing pharmacological therapeutic strategies. Mitochondrial dysfunction and mitophagy defects are observed during senescence and AD, and studies suggest that they might lead to Aβ accumulation. Our goal in this project was to explore if a reduced removal of dysfunctional mitochondria during aging is a key contributor to amyloid pathology and

Alzheimer’s disease (AD) and type 2 diabetes (T2D) share common features, including insulin resistance. Brain insulin resistance has been implicated as a key factor in the pathogenesis of AD. Recent studies have demonstrated that sodium–glucose cotransporter-2 inhibitor (SGLT2-i) and dipeptidyl peptidase-4 inhibitor (DPP4-i) improve insulin sensitivity and provide neuroprotection. However, the effects of these two inhibitors on the brain metabolism and insulin resistance remain uninvestigated.We developed a T2D–AD mouse model using a high-fat diet (HFD) for 19 weeks along with a single dose of

…of two proteins within the brain- amyloid-β which deposits in extracellular plaques and the tau protein which forms neurofibrillary tangles. However, it is tau spreading that best correlates with clinical symptoms in AD, whilst the mechanisms that potentially drive tau spreading remain still unknown. More recently a study has demonstrated that binding of tau fibrils to the extracellular region of the Amyloid Precursor Protein (APP) led to the uptake of tau into cells, suggesting that APP may function as a tau fibril receptor

…also have varying degrees of tau and amyloid-β co-pathology. Identifying and tracking the pathologic heterogeneity of DLB with multi-modal biomarkers is critical for the design of clinical trials that target each pathology early in the disease at a time when prevention or delaying the transition to dementia is possible. Furthermore, longitudinal evaluation of multi-modal biomarkers contributes to our understanding of the type and extent of the pathologic progression and serves to characterize the temp

Glymphatic perivascular exchange is supported by the astroglial water channel aquaporin-4 (AQP4), which localizes to perivascular astrocytic endfeet surrounding the cerebral vasculature. In aging mice, impairment of glymphatic function is associated with reduced perivascular AQP4 localization, yet whether these changes contribute to the development of neurodegenerative disease, such as Alzheimer’s disease (AD), remains unknown. Using post mortem human tissue, we evaluated perivascular AQP4 localization in the frontal cortical gray matter, white matter, and hippocampus of cognitively normal sub

…the accumulation of a toxic form of amyloid-β (Aβ) peptides are linked to mitochondrial impairment. The coenzyme nicotinamide adenine dinucleotide (NAD+) is essential for both mitochondrial bioenergetics and nuclear DNA repair through NAD+-consuming poly (ADP-ribose) polymerases (PARPs). Here, we analysed the metabolomic changes in flies over-expressing Aβ and showed a decrease of metabolites associated with nicotinate and nicotinamide metabolism, which is critic