Intravenous chaperone treatment of late-stage Alzheimer´s disease (AD) mouse model affects amyloid plaque load, reactive gliosis and AD-related genes.

Treatment strategies that are efficient against established Alzheimer's disease (AD) are needed. BRICHOS is a molecular chaperone domain that prevents amyloid fibril formation and associated cellular toxicity. In this study, we treated an AD mouse model seven months after pathology onset, using intravenous administration of recombinant human (rh) Bri2 BRICHOS R221E.

Pro-resolving lipid mediator reduces amyloid-β42-induced gene expression in human monocyte-derived microglia.

JOURNAL/nrgr/04.03/01300535-202503000-00031/figure1/v/2024-06-17T092413Z/r/image-tiff Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β.

Cerebrospinal Fluid Profile of Lipid Mediators in Alzheimer's Disease.

Alzheimer's disease (AD) develops into dementia over a period of several years, during which subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) can be used as intermediary diagnoses of increasing severity. Chronic neuroinflammation resulting from insufficient resolution is involved in the pathogenesis of AD and is associated with cognitive impairment. Specialized pro-resolving lipid mediators (LMs) that promote the resolution of inflammation may be valuable markers in AD diagnosis and as therapeutic targets.

Intranasal delivery of pro-resolving lipid mediators rescues memory and gamma oscillation impairment in App mice.

Sustained microglial activation and increased pro-inflammatory signalling cause chronic inflammation and neuronal damage in Alzheimer's disease (AD). Resolution of inflammation follows neutralization of pathogens and is a response to limit damage and promote healing, mediated by pro-resolving lipid mediators (LMs). Since resolution is impaired in AD brains, we decided to test if intranasal administration of pro-resolving LMs in the App mouse model for AD could resolve inflammation and ameliorate pathology in the brain.

CSF and Plasma Cholinergic Markers in Patients With Cognitive Impairment.

Introduction: Alzheimer's disease (AD) is the most prevalent form of dementia with symptoms of deteriorating cognitive functions and memory loss, partially as a result of a decrease in cholinergic neurotransmission. The disease is incurable and treatment with cholinesterase inhibitors (ChEIs) is symptomatic. Choline acetyltransferase (ChAT), the enzyme that synthesizes acetylcholine (ACh), has been proven recently to be present in both cerebrospinal fluid (CSF) and plasma.

Effects of Peroral Omega-3 Fatty Acid Supplementation on Cerebrospinal Fluid Biomarkers in Patients with Alzheimer's Disease: A Randomized Controlled Trial-The OmegAD Study.

Background: Studies have suggested a connection between a decrease in the levels of polyunsaturated fatty acids (PUFAs) and Alzheimer's disease (AD). We aimed to assess the effect of supplementation with omega-3 fatty acids (n-3 FAs) on biomarkers analyzed in the cerebrospinal fluid (CSF) of patients diagnosed with AD.

Objective: To investigate the effects of daily supplementation with 2.

Age-related changes in brain phospholipids and bioactive lipids in the APP knock-in mouse model of Alzheimer's disease.

Sustained brain chronic inflammation in Alzheimer's disease (AD) includes glial cell activation, an increase in cytokines and chemokines, and lipid mediators (LMs), concomitant with decreased pro-homeostatic mediators. The inflammatory response at the onset of pathology engages activation of pro-resolving, pro-homeostatic LMs followed by a gradual decrease. We used an APP knock-in (App KI) AD mouse that accumulates β-amyloid (Aβ) and presents cognitive deficits (at 2 and 6 months of age, respectively) to investigate LMs, their precursors, biosynthetic enzymes and receptors, glial activation, and inflammatory proteins in the cerebral cortex and hippocampus at 2-, 4-, 8- and 18-month-old in comparison with wild-type (WT) mice.

Cerebrospinal Fluid Inflammatory Markers in Alzheimer's Disease: Influence of Comorbidities.

Background: Alzheimer's disease (AD) develops into dementia after several years, and subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are used as intermediary diagnoses of increasing severity. Inflammation is an important part of AD pathology and provides potential novel biomarkers and treatment targets.

Objective: To identify novel potential biomarkers of AD in cerebrospinal fluid (CSF) and create a molecular pattern of inflammatory factors providing differentiation between AD and SCI.

Plasma Resolvin D2 to Leukotriene B Ratio Is Reduced in Diabetic Patients with Ischemic Stroke and Related to Prognosis.

Background: Diabetes mellitus (DM) aggravates symptoms and prognosis of acute ischemic stroke (AIS), and inflammation plays an important role therein. Resolvin D2 (RvD2) is one of the specialized pro-resolving mediators (SPMs), while leukotriene B (LTB) is a classic proinflammatory mediator. The ratio of RvD2 to LTB is an index of pro-resolving/proinflammatory balance.

Subgingival microbiota in a population with and without cognitive dysfunction.

: The aim of this study was to compare the subgingival microbiota of people with Alzheimer´s disease (AD), mild cognitive impairment (MCI), subjective cognitive decline (SCD) and cognitively healthy individuals. : The study population was recruited from 2013 to 2017 and comprised 132 cases recently diagnosed with AD (n = 46), MCI (n = 40) or SCD (n = 46), and 63 cognitively healthy controls. Subgingival samples were collected, and the microbiotas were characterized by gene sequencing.

Role of polyunsaturated fatty acids in ischemic stroke - A perspective of specialized pro-resolving mediators.

Polyunsaturated fatty acids (PUFAs) have been proposed as beneficial for cardiovascular health. However, results from both epidemiological studies and clinical trials have been inconsistent, whereas most of the animal studies showed promising benefits of PUFAs in the prevention and treatment of ischemic stroke. In recent years, it has become clear that PUFAs are metabolized into various types of bioactive derivatives, including the specialized pro-resolving mediators (SPMs).

Reduced Levels of Plasma Lipoxin A4 Are Associated with Post-Stroke Cognitive Impairment.

Background: Specialized pro-resolving mediators (SPMs) are bioactive lipids derived from n-3 and n-6 polyunsaturated fatty acids. SPMs promote resolution of inflammation and are reduced in Alzheimer's disease. It is unknown whether SPMs are associated with post-stroke cognitive impairment (PSCI).

Maresin 1 attenuates pro-inflammatory activation induced by β-amyloid and stimulates its uptake.

Alzheimer's disease (AD) is the most common dementia, characterized by pathological accumulation of β-amyloid (Aβ) and hyperphosphorylation of tau protein, together with a damaging chronic inflammation. The lack of effective treatments urgently warrants new therapeutic strategies. Resolution of inflammation, associated with beneficial and regenerative activities, is mediated by specialized pro-resolving lipid mediators (SPMs) including maresin 1 (MaR1).

Chronic Airway Allergy Induces Pro-Inflammatory Responses in the Brain of Wildtype Mice but Not 3xTgAD Mice.

The effects of systemic inflammation on the pathogenesis of Alzheimer's disease (AD) are not clarified, both beneficial and deleterious effects being reported. Allergy is accompanied by a systemic inflammatory response and some epidemiological studies have reported a positive association between a history of allergy/asthma and dementia. To investigate whether chronic airway allergy influences the inflammatory status in the brain, AD-like pathology, and behaviour in relation to AD, we induced chronic airway allergy in triple transgenic AD (3xTgAD) and wildtype (WT) mice by repeated exposure to ovalbumin (OVA) as allergen.

RvE1 treatment prevents memory loss and neuroinflammation in the Ts65Dn mouse model of Down syndrome.

Inflammation can be resolved by pro-homeostatic lipids called specialized pro-resolving mediators (SPMs) upon activation of their receptors. Dysfunctional inflammatory resolution is now considered as a driver of chronic neuroinflammation and Alzheimer's disease (AD) pathogenesis. We have previously shown that SPM levels were reduced and also that SPM-binding receptors were increased in patients with AD compared to age-matched controls.

Receptors for pro-resolving mediators are increased in Alzheimer's disease brain.

Neuroinflammation is a key element of AD pathology and conceivably a result of a disturbed resolution. Resolution of inflammation is an active process which is strictly orchestrated following the acute inflammatory response after removal of the inflammatory stimuli. Acute inflammation is actively terminated by specialized pro-resolving mediators (SPMs) thereby promoting healing and return to homeostasis.

Homocysteine Status Modifies the Treatment Effect of Omega-3 Fatty Acids on Cognition in a Randomized Clinical Trial in Mild to Moderate Alzheimer's Disease: The OmegAD Study.

Background: Trials of supplementation with omega-3 fatty acids (ω3-FAs) in patients with mild cognitive impairment or Alzheimer's disease (AD) have produced inconsistent effects on cognitive decline. There is evidence of an interaction between B vitamin status and ω3-FAs in relation to brain atrophy and cognitive decline.

Objective: We investigated whether baseline levels of plasma total homocysteine (tHcy), a marker of B vitamin status, modify the effects of ω3-FAs supplementation on cognitive performance in moderate AD.

Association between periodontitis and risk of Alzheimer's disease, mild cognitive impairment and subjective cognitive decline: A case-control study.

Aims: To test the hypothesis that periodontal disease contributes to increased risk of mild cognitive impairment (MCI), subjective cognitive decline (SCD) and Alzheimer's disease (AD).

Materials And Methods: This case-control study was conducted over a 3-year period in the municipality of Huddinge, Sweden. In total, 154 cases were consecutively enrolled from the Karolinska Memory Clinic at the Karolinska University Hospital and allotted to three diagnostic groups: AD, MCI and SCD, collectively referred to as "cases.

Can inflammation be resolved in Alzheimer's disease?

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and dementia. Accumulating evidence suggests that inflammation is involved in the pathogenesis of AD. Epidemiological studies suggest that use of anti-inflammatory drugs is associated with a lower incidence of AD.

Does Fatty Acid Composition in Subcutaneous Adipose Tissue Differ between Patients with Alzheimer's Disease and Cohabiting Proxies?

Low tissue levels of the major marine ω3 fatty acids (FAs) DHA and EPA are found in Alzheimer's disease (AD). We investigated if healthy proxies to AD patients have higher levels of these ω3 FAs. We observed lower levels of EPA and DHA in subcutaneous adipose tissue biopsies from 64 AD patients compared with 16 cognitively healthy proxies.

Synthesis and in Vitro Evaluation of Monodisperse Amino-Functional Polyester Dendrimers with Rapid Degradability and Antibacterial Properties.

Amine functional polymers, especially cationically charged, are interesting biomacromolecules for several reasons, including easy cell membrane entrance, their ability to escape endosomes through the proton sponge effect, spontaneous complexation and delivery of drugs and siRNA, and simple functionalization in aqueous solutions. Dendrimers, a subclass of precision polymers, are monodisperse and exhibit a large and exact number of peripheral end groups in relation to their size and have shown promise in drug delivery, biomedical imaging and as antiviral agents. In this work, hydroxyl functional dendrimers of generation 1 to 5 based on 2,2-bis(methylol)propionic acid (bis-MPA) were modified to bear 6 to 96 peripheral amino groups through esterification reactions with beta-alanine.

DHA-rich n-3 fatty acid supplementation decreases DNA methylation in blood leukocytes: the OmegAD study.

Dietary fish oils, rich in long-chain n-3 (ω-3) fatty acids (FAs) [e.g., docosahexaenoic acid (DHA, 22:6n-3) and eicosapentaenoic acid (EPA, 20:5n-3)], modulate inflammatory reactions through various mechanisms, including gene expression, which is measured as messenger RNA concentration.

Detrimental effects of a high fat/high cholesterol diet on memory and hippocampal markers in aged rats.

High fat diets have detrimental effects on cognitive performance, and can increase oxidative stress and inflammation in the brain. The aging brain provides a vulnerable environment to which a high fat diet could cause more damage. We investigated the effects of a high fat/high cholesterol (HFHC) diet on cognitive performance, neuroinflammation markers, and phosphorylated Tau (p-Tau) pathological markers in the hippocampus of Young (4-month old) versus Aged (14-month old) male rats.