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The present note describes a historical occurrence and distribution extension of the species Trachelyopteruslucenai in coastal basins, state of Rio Grande do Sul, Brazil.

Aims: Parkinson's disease and related disorders are devastating neurodegenerative pathologies. Since α‐synuclein was identified as a main component of Lewy bodies and neurites, efforts have been made to clarify the pathogenic mechanisms of α‐synuclein's detrimental effects. α‐synuclein oligomers are the most harmful species and may recruit and activate glial cells. Inflammation is emerging as a bridge between genetic susceptibility and environmental factors co‐fostering Parkinson's disease. However, direct evidence linking inflammation to the harmful activities of α‐synuclein oligomers or to the Parkinson's disease behavioural phenotype is lacking. Methods: To clarify whether neuroinflammation influences Parkinson's disease pathogenesis, we developed: (i) a 'double‐hit' approach in C57BL/6 naive mice where peripherally administered lipopolysaccharides were followed by intracerebroventricular injection of an inactive oligomer dose; (ii) a transgenic 'double‐hit' model where lipopolysaccharides were given to A53T α‐synuclein transgenic Parkinson's disease mice. Results: Lipopolysaccharides induced a long‐lasting neuroinflammatory response which facilitated the detrimental cognitive activities of oligomers. LPS‐activated microglia and astrocytes responded differently to the oligomers with microglia activating further and acquiring a pro‐inflammatory M1 phenotype, while astrocytes atrophied. In the transgenic 'double‐hit' A53T mouse model, lipopolysaccharides aggravated cognitive deficits and increased microgliosis. Again, astrocytes responded differently to the double challenge. These findings indicate that peripherally induced neuroinflammation potentiates the α‐synuclein oligomer's actions and aggravates cognitive deficits in A53T mice. Conclusions: The fine management of both peripheral and central inflammation may offer a promising therapeutic approach to prevent or slow down some behavioural aspects in α‐synucleinopathies. [ABSTRACT FROM AUTHOR]

We evaluated the effects of timing of estrogenic implant insertion, relative to weaning, on growth performance and measurements of innate and humoral immunity of beef calves. On d -14, Angus ? Simmental crossbred steers (n = 48; BW = 217 ± 5 kg; age = 191 ± 3 d) were stratified by BW, age, and cow parity and randomly assigned to receive no implant (NOIP) or 36 mg of zeranol on d -14, 0, or 14, relative to weaning (IP-14, IP0, and IP+14, respectively; 12 steers/treatment). From d -14 to 0, cow-calf pairs remained on a single, tall-fescue pasture with no access to concentrate supplementation. Steers were weaned on d 0, stratified by treatment and BW, and then allocated into 1 of 16 drylot pens to receive daily freechoice access to a corn silage-based diet during the preconditioning phase (d 0 to 56). Steers were vaccinated against infectious bovine rhinotracheitis (IBRV), bovine viral diarrhea virus (BVDV), and Clostridium on d -27 and 0. From d 56 to 252 (postpreconditioning phase), steers remained in their respective feedlot pens and were provided free-choice access to corn silage- based growing (d 56 to 167) and finishing total mixed rations (d 168 to 252). Body weight on d 0 did not differ among treatments (P ≥ 0.29) but was greater for IP-14 and IP0 than NOIP and IP+14 steers on d 14, 42, and 56 (P ≤ 0.05). Treatment effects were not detected for G:F and DMI from d 0 to 56 (P ≥ 0.34), but ADG from d -14 to 56 was greater for IP-14 compared to NOIP (P ≤ 0.05) and intermediate for IP0 and IP+14 steers. Plasma IGF-1 concentrations were greater for IP-14 than NOIP (P ≤ 0.05) and intermediate for IP0 and IP+14 steers on d -7, 0, 14, and 21. Plasma concentrations of cortisol and haptoglobin and serum titers against BVDV types 1a and 2 did not differ among treatments from d 0 to 56 (P ≥ 0.37). However, serum IBRV titers were greater for IP+14 than NOIP, IP-14, and IP0 steers (P ≤ 0.02). On d 252, BW was greater for IP-14 and IP0 than NOIP steers (P ≤ 0.05) and intermediate for IP+14 steers, but ADG and G:F from d 57 to 252 and carcass characteristics at slaughter did not differ among treatments (P ≥ 0.16). Thus, the 36-mg zeranol implant did not elicit an inflammatory response or affect the overall vaccine response of steers (except for IBRV titers). However, growth of steers during a 56-d preconditioning period was enhanced by administering 36-mg zeranol implant 14 d before weaning, without affecting subsequent postpreconditioning growth and carcass characteristics at slaughter. [ABSTRACT FROM AUTHOR]

This study evaluated growth and measurements of innate and humoral immunity of preconditioning beef heifers supplemented with wet brewers grains (WBG) at 2 supplementation rates and frequencies. At 14 d after weaning (d 0), Angus heifers (n = 36; 213 ± 2 kg BW and 254 ± 7 d of age) were stratified by BW and age and randomly assigned to 1 of 12 drylot pens (3 heifers/pen). Treatments were randomly assigned to pens, in a 2 × 2 factorial design, and consisted of heifers provided ground tall fescue hay ad libitum (55% TDN and 12% CP of DM) and supplemented with WBG (75% TDN and 36% CP of DM) either daily (7X) or 3 times weekly (3X; Monday, Wednesday, and Friday) at 0.5 or 1.0% of BW (DM basis) for 42 d. Heifers were vaccinated against infectious bovine rhinotracheitis (IBR), bovine viral diarrhea virus (BVDV), Mannheimia haemolytica, and Clostridium on d 14 and 28. Individual BW was measured before feeding on d 0 and 42 following 12 h of feed and water withdrawal. Blood samples were collected via jugular venipuncture 4 h after WBG supplementation on d 14, 15, 16, 17, 21, 28, 29, 30, 31, 35, and 42. Heifers fed WBG 3X had less hay DMI (2.6 ± 0.16 vs. 3.2 ± 0.16 kg/d; P < 0.0001) but greater total DMI (5.6 ± 0.16 vs. 3.8 ± 0.16 kg/d; P < 0.0001) than 7X heifers on days that all heifers received WBG supplementation. However, overall hay and total DMI was not affected (P = 0.40) by supplementation frequency. Therefore, ADG, BW, and G:F from d 0 to 42 did not differ among treatments (P ≥ 0.29). Plasma concentrations of haptoglobin on d 15 and cortisol on d 14 were greater for 3X heifers vs. 7X heifers (P ≤ 0.04). Heifers fed WBG at 0.5% of BW tended to have greater plasma cortisol concentrations on d 15, 17, and 35 (P ≤ 0.09) than heifers fed at 1.0% of BW. Serum BVDV-1a titers were greater (P = 0.04) for 7X heifers vs. 3X heifers on d 42 (4.2 ± 0.28 vs. 3.3 ± 0.28 log2), whereas serum titers against BVDV- 2 and IBR were greater for heifers fed WBG at 1.0% of BW vs. heifers fed WBG at 0.5% of BW (7.6 vs. 6.7 and 3.3 vs. 2.8 ± 0.19 log2, respectively). In summary, decreasing WBG supplementation frequency (7 vs. 3 times weekly) or rate (1.0 vs. 0.5% of BW) for recently weaned beef heifers did not affect growth but decreased vaccine-induced antibody production against pathogens associated with bovine respiratory disease during a 42-d preconditioning period. [ABSTRACT FROM AUTHOR]

Our objectives were to evaluate postnatal growth and measurements of innate and humoral immunity of beef calves born to dams fed wet brewers grains (WBG) daily or 3 times weekly during late gestation. On d 0 (approximately 60 d before calving), 28 multiparous, spring-calving Angus cows (BW = 578 ± 19 kg; age = 4.7 ± 0.65 yr; BCS = 7.0 ± 0.18) were stratified by sire, age, BW, and BCS and then randomly allocated into 1 of 14 drylot pens (2 cows/pen; 18 by 3 m; 27 m2/cow). Cows were offered ground tall fescue hay ad libitum and received similar weekly WBG supplementation (DMI = 0.5% of BW multiplied by 7 d). Treatments were randomly assigned to pens (7 pens/treatment) and consisted of cows receiving WBG supplementation daily (S7; weekly DMI of WBG divided by 7 d) or 3 times weekly (S3; weekly DMI of WBG divided by 3 d; Mondays, Wednesdays, and Fridays) from d 0 until calving. Cow-calf pairs were managed as a single group on tall fescue pastures from calving to weaning (d 226). Calves were immediately submitted to a preconditioning period from d 226 to 266 and vaccinated against infectious bovine rhinotracheitis, bovine viral diarrhea virus, Mannheimia haemolytica, and Clostridium on d 231 and 245. Decreasing the frequency of WBG supplementation did not impact (P ≥ 0.21) precalving intake of total DM, CP, and TDN; BW and BCS change; overall plasma cortisol concentrations; and postcalving growth and pregnancy rate of cows. Overall plasma concentrations of glucose and insulin did not differ (P ≥ 0.28) between S3 and S7 cows, whereas S3 cows had greater (P = 0.002) plasma glucose concentrations and tended (P = 0.06) to have greater plasma insulin concentrations on days they were not fed WBG vs. days of WBG supplementation. Calf plasma concentrations of haptoglobin and cortisol at birth but not serum IgG (P = 0.63) tended (P = 0.10) to be greater for S3 vs. S7 calves. However, additional calf growth and immunity variables obtained during preand postweaning phases did not differ between S3 and S7 calves (P ≥ 0.21). Hence, decreasing the frequency of WBG supplementation during late gestation caused oscillations on precalving plasma glucose and insulin concentrations but did not affect plasma cortisol concentrations, growth, and pregnancy rate of cows. Also, reduced frequency of WBG supplementation during late gestation did not have carryover effects on postnatal calf growth and immunity. [ABSTRACT FROM AUTHOR]

Our objectives were to evaluate the pre- and postweaning growth and measurements of innate and humoral immune response of beef calves born to cows fed 70 or 100% of NEm requirements during the last 40 d of gestation. On d 0 (approximately 40 d before calving), 30 multiparous Angus cows pregnant to embryo transfer (BW = 631 ± 15 kg; age = 5.2 ± 0.98 yr; BCS = 6.3 ± 0.12) were randomly allocated into 1 of 10 drylot pens (3 cows/ pen). Treatments were randomly assigned to pens (5 pens/treatment) and consisted of cows limit-fed (d 0 to calving) isonitrogenous, total-mixed diets formulated to provide 100 (CTRL) or 70% (REST) of daily NEm requirements of a 630-kg beef cow at 8 mo of gestation. Immediately after calving, all cow-calf pairs were combined into a single management group and rotationally grazed on tall fescue pastures (6 pastures; 22 ha/pasture) until weaning (d 266). All calves were assigned to a 40-d preconditioning period in a drylot from d 266 to 306 and vaccinated against infectious bovine rhinotracheitis, bovine viral diarrhea virus (BVDV), Mannheimia haemolytica, and Clostridium spp. on d 273 and 287. Blood samples from jugular vein were collected from cows on d 0, 17, and 35 and from calves within 12 h of birth and on d 266, 273, 274, 276, 279, and 287. By design, REST cows consumed less (P ≤ 0.002) total DMI, TDN, and NEm but had similar CP intake (P = 0.67), which tended (P = 0.06) to increase BW loss from d 0 to calving, than CTRL cows (-1.09 vs. -0.70 ± 0.14 kg/d, respectively). However, gestational NEm intake did not affect (P ≥ 0.30) plasma concentrations of cortisol, insulin, and glucose during gestation and BCS at calving as well as postcalving pregnancy rate, BW, and BCS change of cows. Calf serum IgG concentrations and plasma concentrations of haptoglobin and cortisol at birth as well as calf pre- and postweaning BW and ADG did not differ (P ≥ 0.15) between calves born to REST and CTRL cows. However, calf postweaning overall plasma concentrations of cortisol; plasma haptoglobin concentrations on d 274, 276, and 279; and serum BVDV-1a titers on d 306 were less for REST calves than for CTRL calves (P ≤ 0.05). Hence, a NEm restriction to 70% of daily requirements during the last 40 d of gestation had minimal effects on cow precalving growth and did not affect postcalving cow growth and reproductive performance. However, it decreased postweaning vaccination-induced humoral immunity, inflammatory, and physiological stress responses of calves. [ABSTRACT FROM AUTHOR]

We evaluated the effects of frequency of energy supplementation on growth and measurements of innate and humoral immune responses of preconditioning beef steers following vaccination. Angus steers (n = 24; 221 ± 6.3 kg; 177 ± 4 d of age) were weaned on d -7 and kept in a single drylot pen with free access to tall fescue hay and concentrate DMI at 0.5% of BW (50:50 mix of soyhulls and corn gluten pellets; DM basis) from d -7 to 0. On d 0, steers were stratified by BW and age and randomly assigned to 1 of 8 feedlot pens (3 steers/pen). Treatments were randomly assigned to pens (4 pens/treatment) and consisted of steers provided daily free access to ground tall fescue hay and similar weekly concentrate DMI (1% of BW times 7 d), which was divided and offered either daily (S7) or 3 times weekly (S3; Monday, Wednesday, and Friday) from d 0 to 42. Individual BW was measured before feeding on d 0 and 42, after 12 h of feed and water withdrawal. Steers were vaccinated against infectious bovine rhinotracheitis, bovine viral diarrhea virus (BVDV), Mannheimia haemolytica, and clostridium on d 7 and 21. Blood samples were collected from the jugular vein on d -7 and 4 h after concentrate supplementation on d 0, 7, 8, 9, 10, 14, 21, 22, 23, 24, 28, 35, and 42. Steers offered concentrate daily had greater (P = 0.02) BW on d 42, overall ADG, and total DMI, but similar (P = 0.14) G:F, than S3 steers. On days that S7 and S3 steers were offered concentrate, total DMI was greater and hay DMI was less for S3 vs. S7 steers (P = 0.05). On days that only S7 steers were supplemented, hay DMI was greater, but total DMI was less for S3 vs. S7 steers (P = 0.05). Mean CP and NEg intake were greater (P = 0.03) for S7 vs. S3 steers. Plasma cortisol concentrations on d 7 and 28, and mean plasma haptoglobin concentrations, but not liver mRNA expression of haptoglobin (P = 0.75), were greater for S3 vs. S7 steers (P = 0.03). Plasma IGF-1 concentrations on d 0 and urea nitrogen on d 1 and 3, relative to vaccination, were greater for S7 vs. S3 steers (P = 0.008). Positive seroconversion to BVDV-1b on d 42 and mean serum BVDV-1b titers were greater for S7 vs. S3 steers (P = 0.05). In summary, decreasing the frequency of concentrate supplementation from daily to three times weekly, during a 42-d preconditioning period, decreased growth performance, increased plasma concentrations of haptoglobin and cortisol, and decreased vaccine-induced antibody production against BVDV-1b of beef steers. [ABSTRACT FROM AUTHOR]

We evaluated the effects of MP supply on growth performance before and after preconditioning and measurements of innate and humoral immune response of beef steers following vaccination. Angus steers (n = 36; BW = 231 ± 21 kg; age = 184 ± 18 d) were weaned on d -6, stratified by BW and age on d 0, and randomly assigned to 1 of 18 drylot pens (2 steers/pen). Treatments were assigned to pens (6 pens/ treatment) and consisted of corn silage-based diets formulated to provide 85%, 100%, or 115% of the daily MP requirements of a beef steer gaining 1.1 kg/d from d 0 to 42. Steers were vaccinated against infectious bovine rhinotracheitis virus, bovine viral diarrhea (BVDV) types 1 and 2 viruses, Mannheimia haemolytica, and clostridium on d 14 and 28. Blood samples were collected on d 0, 14, 15, 17, 21, 28, 29, 30, 35, and 42. Body weight did not differ (P = 0.17) among treatments from d 0 to 28. On d 42, 115% MP steers were heaviest, 100% MP steers were intermediate, and 85% MP steers were lightest (P = 0.05; 297, 290, and 278 ± 7 kg, respectively). Overall, ADG and G:F did not differ (P = 0.13) between 100% and 115% MP steers and were least (P < 0.01) for 85% MP steers (1.2, 1.4, and 0.8 ± 0.07 kg/d and 0.23, 0.24, and 0.19 ± 0.008, respectively). Plasma haptoglobin (Hp) concentrations did not differ among treatments (P = 0.46), whereas plasma ceruloplasmin (Cp) concentrations were greatest (P = 0.04) for 85% MP steers, intermediate for 100% MP steers, and least for 115% MP steers on d 30, 35, and 42. Plasma cortisol concentrations were greater (P = 0.03) for 85% vs. 100% and 115% MP steers on d 14 and 28. Liver mRNA expression of Cp and Hp and muscle mRNA expression of m-calpain, mammalian target of rapamycin, and ubiquitin did not differ among treatments (P = 0.17). Serum neutralization titers to BVDV-1b titers were greater (P = 0.02) for 115% vs. 85% and 100% MP steers on d 42 (5.8, 3.0, and 3.7 ± 0.60 log2, respectively), whereas mean serum M. haemolytica leukotoxin titers were greater for 85% vs. 100% and 115% MP steers (3.1, 2.4, and 2.5 ± 0.21 log2, respectively). Preconditioning MP supply did not affect (P = 0.26) subsequent finishing growth performance and carcass characteristics. Thus, increasing MP supply from 85% to 115% of daily requirement of preconditioning beef steers had variable results on innate and humoral immune response and enhanced growth performance during a 42-d preconditioning period without affecting carcass characteristics at slaughter. [ABSTRACT FROM AUTHOR]

Frailty is a geriatric, multi-dimensional syndrome that reflects multisystem physiological change and is a transversal measure of reduced resilience to negative events. It is characterized by weakness, frequent falls, cognitive decline, increased hospitalization and dead and represents a risk factor for the development of Alzheimer's disease (AD). The fact that frailty is recognized as a reversible condition encourages the identification of earlier biomarkers to timely predict and prevent its occurrence. SAMP8 (Senescence-Accelerated Mouse Prone-8) mice represent the most appropriate preclinical model to this aim and were used in this study to carry transcriptional and metabolic analyses in the brain and plasma, respectively, upon a characterization at cognitive, motor, structural, and neuropathological level at 2.5, 6, and 9 months of age. At 2.5 months, SAMP8 mice started displaying memory deficits, muscle weakness, and motor impairment. Functional alterations were associated with a neurodevelopmental deficiency associated with reduced neuronal density and glial cell loss. Through transcriptomics, we identified specific genetic signatures well distinguishing SAMP8 mice at 6 months, whereas plasma metabolomics allowed to segregate SAMP8 mice from SAMR1 already at 2.5 months of age by detecting constitutively lower levels of acylcarnitines and lipids in SAMP8 at all ages investigated correlating with functional deficits and neuropathological signs. Our findings suggest that specific genetic alterations at central level, as well as metabolomic changes in plasma, might allow to early assess a frail condition leading to dementia development, which paves the foundation for future investigation in a clinical setting., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background and Purpose: Parkinson's disease remains orphan of valuable therapies capable to interfere with the disease pathogenesis despite the large number of symptomatic approaches adopted in clinical practice to manage this disease. Treatments simultaneously affecting α-synuclein (α-syn) oligomerization and neuroinflammation may counteract Parkinson's disease and related disorders. Recent data demonstrate that Doxycycline, a tetracycline antibiotic, can inhibit α-syn aggregation as well as neuroinflammation. We herein investigate, for the first time, the potential therapeutic properties of Doxy in a human α-syn A53T transgenic Parkinson's disease mouse model evaluating behavioural, biochemical and histopathological parameters., Experimental Approach: Human α-syn A53T transgenic mice were treated with Doxycycline (10 mg/kg daily ip) for 30 days. The effect of treatment on motor, cognitive and daily live activity performances were examined. Neuropathological and neurophysiological parameters were assessed through immunocytochemical, electrophysiological and biochemical analysis of cerebral tissue., Key Results: Doxy treatment abolished cognitive and daily life activity deficiencies in A53T mice. The effect on cognitive functions was associated with neuroprotection, inhibition of α-syn oligomerization and gliosis both in the cortex and hippocampus. Doxy treatment restored hippocampal long-term potentiation in association with the inhibition of pro-inflammatory cytokines expression. Moreover, Doxy ameliorated motor impairment and reduced striatal glial activation in A53T mice., Conclusions and Implications: Our findings promote Doxy as a valuable multi-target therapeutic approach counteracting both symptoms and neuropathology in the complex scenario of α-synucleinopathies., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: In chronic kidney disease (CKD), the high morbidity and mortality risk for cardiovascular disease (CVD) are not easily explained only on the basis of traditional factors. Among nontraditional ones involved in CKD, malnutrition, inflammation, and atherosclerosis/calcification have been described as the "MIA syndrome.", Methods: In this pilot study, we evaluated the association between the variation in serum levels of 27 uremic retention solutes plus 6 indexes related to the MIA syndrome processes in a population of dialysis patients., Results: As expected, we found a direct correlation between serum albumin and both phosphate and total cholesterol (r = 0.54 and 0.37, respectively; p < 0.05). Moreover, total cholesterol and phosphate directly correlate (r = 0.40, p < 0.05). The relationship between malnutrition and inflammation is highlighted by the correlation of serum cholesterol levels with serum alpha-1 acid glycoprotein and IL-6 levels (r = -0.56, r = -0.39, respectively; p < 0.05). Moreover, the relation between inflammation and atherosclerosis/calcification is supported by the correlation of IL-6 with VEGF levels and vascular smooth muscle cell high-Pi in vitro calcification (r = 0.81, r = 0.66, respectively; p < 0.01)., Conclusion: We found significant correlations between several uremic retention solutes and malnutrition, inflammation, and atherosclerosis/calcification. Our findings support the hypothesis of a central role of the uremic milieu in the MIA syndrome and ultimately in the pathogenesis of CKD-specific CVD risk factors., (© 2022 S. Karger AG, Basel.)

A cytokine storm drives the pathogenesis of severe COVID-19 infection and several biomarkers have been linked to mortality. Chronic kidney disease (CKD) emerged as a risk factor for severe COVID-19. We investigated the association between selected biomarkers and mortality in 77 patients hospitalized for COVID-19, and whether they differ in patients with eGFR higher and lower than 45 mL/min. The association between patients’ characteristics, plasma biomarkers and mortality was conducted by univariate logistic regression models and independent predictors of mortality were then used to create a multivariate prediction model through Cox regression. Patients with lower eGFR had a significant increase of GDF-15, CD-25 and RAGE, with higher plasma levels in non-survivors and in patients who needed ventilation. At univariate analysis, low and mid-low GDF-15 quartiles (<4.45 ng/mL) were associated with lower mortality risk, while mid-high and high quartiles (>4.45 ng/mL) were associated with higher mortality risk. Independent association between GDF-15 quartiles and mortality risk was confirmed in the Cox model and adjusted for eGFR, age, fever and dyspnea (HR 2.28, CI 1.53−3.39, p < 0.0001). The strength of the association between GDF-15 quartiles and mortality risk increased in patients with lower compared to higher eGFR (HR 2.53, CI 1.34−4.79 versus HR 1.99, CI 1.17−3.39). Our findings may suggest a further investigation of the effect of GDF-15 signaling pathway inhibition in CKD.

Mechanisms of tissue damage in Huntington's disease involve excitotoxicity, mitochondrial damage, and inflammation, including microglia activation. Immunomodulatory and anti-protein aggregation properties of tetracyclines were demonstrated in several disease models. In the present study, the neuroprotective and anti-inflammatory effects of the tetracycline doxycycline were investigated in the mouse model of HD disease R6/2. Transgenic mice were daily treated with doxycycline 20 mg/kg, starting from 4 weeks of age. After sacrifice, histological and immunohistochemical studies were performed. We found that doxycycline-treated R6/2 mice survived longer and displayed less severe signs of neurological dysfunction than the saline-treated ones. Primary outcome measures such as striatal atrophy, neuronal intranuclear inclusions, and the negative modulation of microglial reaction revealed a neuroprotective effect of the compound. Doxycycline provided a significantly increase of activated CREB and BDNF in the striatal neurons, along with a down modulation of neuroinflammation, which, combined, might explain the beneficial effects observed in this model. Our findings show that doxycycline treatment could be considered as a valid therapeutic approach for HD.

Scope: Amyloid-β oligomers (AβO) are causally related to Alzheimer's disease (AD). Dietary natural compounds, especially flavonoids and flavan-3-ols, hold great promise as potential AD-preventive agents but their host and gut microbiota metabolism complicates identification of the most relevant bioactive species. This study aims to investigate the ability of a comprehensive set of phenyl-γ-valerolactones (PVL), the main circulating metabolites of flavan-3-ols and related dietary compounds in humans, to prevent AβO-mediated toxicity., Methods and Results: The anti-AβO activity of PVLs is examined in different cell model systems using a highly toxic β-oligomer-forming polypeptide (β23) as target toxicant. Multiple PVLs, and particularly the monohydroxylated 5-(4'-hydroxyphenyl)-γ-valerolactone metabolite [(4'-OH)-PVL], relieve β-oligomer-induced cytotoxicity in yeast and mammalian cells. As revealed by atomic force microscopy (AFM) and other in vitro assays, (4'-OH)-PVL interferes with AβO (but not fibril) assembly and actively remodels preformed AβOs into nontoxic amorphous aggregates. In keeping with the latter mode of action, treatment of AβOs with (4'-OH)-PVL prior to brain injection strongly reduces memory deterioration as well as neuroinflammation in a mouse model of AβO-induced memory impairment., Conclusion: PVLs, which have been validated as biomarkers of the dietary intake of flavan-3-ols, lend themselves as novel AβO-selective, candidate AD-preventing compounds., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)