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Reasons for performing study: Medial meniscal injuries and subchondral cystic lesions (SCL) are known to occur independently within the medial femorotibial (MFT) joint in horses. However, there are no reports of a potential clinical relationship between these 2 types of lesions. Objectives: To: 1) document the concurrent presence or sequential development of medial meniscal and SCL of the medial femoral condyle within the MFT joint; and 2) determine the prognosis with both types of lesions. Methods: Retrospective case series of horses with both a medial meniscal and SCL of the medial femoral condyle identified concurrently or sequentially by radiography, arthroscopy or post mortem examination. Case records and radiographs were reviewed, and a telephone survey of referring veterinarians, owners and trainers was conducted. Results: Twenty-one horses (9.1% of all horses undergoing MFT joint arthroscopy) were identified to have both a medial meniscal injury and SCL of the medial femoral condyle. Thirteen horses had both abnormalities identified concurrently, 6 developed a meniscal lesion subsequent to SCL debridement, and 2 developed a SCL subsequent to a medial meniscal injury. Only 4/19 horses were classified as successful and returned to their intended use. The severity of the meniscal injury was significantly associated with the severity of lameness but not with outcome. Conclusions: A low percentage of horses may develop both a meniscal injury and SCL of the medial femoral condyle within the MFT joint and have a poor prognosis. Potential relevance: Trauma to the MFT joint may lead to both meniscal and subchondral bone damage of the medial femoral condyle that may be recognised concurrently or sequentially. [ABSTRACT FROM AUTHOR]

Background/purpose: This work was performed to optimize extraction conditions for D-Squame® tape skin samples for use in the skin multiple analyte profile (SkinMAP) method, a Linco Research Corporation bead-based assay for skin analytes. The experiments were designed to help identify sources of variability during extraction that may be amenable to further control. Methods: Two experimental designs were used to study factors influencing the extraction of skin samples from D-Squame® tapes. Visually healthy skin samples were obtained from both female and male adult volar forearms. Factors studied in two experiments included: four surfactant (SDS) levels (0.02–0.2%), two buffer types [Citrate-phosphate buffered saline at pH 5.5, phosphate-buffered saline (PBS) at pH 7.4], two buffer volumes (1.0, 1.5 mL), two propylene glycol (PG) levels (0.1%, 1.0%), two extraction temperatures (7–10°C, 22–30+°C), two extraction times (30, 60 min), and location in sonication bath (two vectors). The response biomarkers were cortisol, fibronectin, human serum albumin, involucrin, keratin-6 and keratins 1, 10. Skin sampling sites were also evaluated as sources of variation. Results: There was no single set of extraction conditions in our experiments that maximized recovery of all the biomarkers. SDS level had the most consistently significant ( P<0.05) and directional effects on biomarker recoveries. In general, higher SDS resulted in higher recovery of all biomarkers. There was less consistency and fewer significant results for the other extraction factors. Conclusions: These data enable us to better manage SkinMAP studies and interpret their results. The use of 1.5 mL PBS containing 0.2% SDS and 0.5% PG with 30 min sonication at low (near 4°C) temperature is optimal for the quantitation of a range of SkinMAP analytes. In order to protect researchers from obtaining inflated false positive rates, it is crucial to design such studies and analyze the data using appropriate statistical methodology, especially for those studies involving only a small number of subjects. [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to determine the clinical effectiveness and cost-effectiveness of three antibiotic regimens for the treatment of pelvic inflammatory disease and tuboovarian abscess.Study Design: A review of all patients' hospitalized at Hutzel Hospital, Detroit, Michigan, for treatment of pelvic inflammatory disease and tuboovarian abscess between Jan. 1, 1993, and April 30, 1997, was performed. Demographic data, antibiotic choices, changes in therapy, operative interventions, and cost of therapy were assessed.Results: Two hundred three patients were admitted for treatment of pelvic inflammatory disease during the study period. We were able to evaluate the clinical efficacy of antibiotic treatment in 179 patients, including 105 patients with pelvic inflammatory disease alone (uncomplicated pelvic inflammatory disease) and 74 women whose infection was complicated by tuboovarian abscess. The three antibiotic regimens evaluated were cefotetan plus doxycycline, clindamycin plus gentamicin, and ampicillin plus clindamycin plus gentamicin. All regimens demonstrated comparable efficacy in treating uncomplicated genital tract infections. Ampicillin plus clindamycin plus gentamicin was significantly better than clindamycin plus gentamicin and cefotetan plus doxycycline in treatment of tuboovarian abscess (p = 0.001). Fifteen women with tuboovarian abscess responded to a change to ampicillin plus gentamicin plus clindamycin antibiotic therapy alone. The hospital stay was prolonged by approximately 3 days in women failing to respond to initial antibiotic therapy, and operative interventions were common in this group of patients.Conclusions: Cefotetan plus oral doxycycline is the most cost-effective regimen for treating uncomplicated pelvic inflammatory disease, whereas triple-antibiotic therapy is the treatment of choice in women with tuboovarian abscess. [ABSTRACT FROM AUTHOR]

The results of analyses of the major chemical constituents of Lobatostoma ringens are as follows: water, 71.6% fresh weight; ash, 4.6% dry weight; protein, 64.3% dry weight; glycogen, 4.7% ethanol-extracted dry weight; lipid, 6.4% fresh weight. Histochemical staining revealed glycogen mainly in the parenchyma and musculature, with smaller deposits in the vitelline cells and spermatozoa; neutral lipid was localized in the gastrodermis and excretory system; and the surfaces of the tegument and gastrodermis were reactive for acidic mucopolysaccharides. Protein synthesis was evident in the tegumental cells, gastrodermis, and vitellaria. [ABSTRACT FROM AUTHOR]

BACKGROUND Sodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. The efficacy and safety of a combination of the two compounds in persons with amyotrophic lateral sclerosis (ALS) are not known. METHODS In this multicenter, randomized, double-blind trial, we enrolled participants with definite ALS who had had an onset of symptoms within the previous 18 months. Participants were randomly assigned in a 2:1 ratio to receive sodium phenylbutyratetaurursodiol (3 g of sodium phenylbutyrate and 1 g of taurursodiol, administered once a day for 3 weeks and then twice a day) or placebo. The primary outcome was the rate of decline in the total score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) through 24 weeks. Secondary outcomes were the rates of decline in isometric muscle strength, plasma phosphorylated axonal neurofilament H subunit levels, and the slow vital capacity; the time to death, tracheostomy, or permanent ventilation; and the time to death, tracheostomy, permanent ventilation, or hospitalization. RESULTS A total of 177 persons with ALS were screened for eligibility, and 137 were randomly assigned to receive sodium phenylbutyrate-taurursodiol (89 participants) or placebo (48 participants). In a modified intention-to-treat analysis, the mean rate of change in the ALSFRS-R score was -1.24 points per month with the active drug and -1.66 points per month with placebo (difference, 0.42 points per month; 95% confidence interval, 0.03 to 0.81; P=0.03). Secondary outcomes did not differ significantly between the two groups. Adverse events with the active drug were mainly gastrointestinal. CONCLUSIONS Sodium phenylbutyrate-taurursodiol resulted in slower functional decline than placebo as measured by the ALSFRS-R score over a period of 24 weeks. Secondary outcomes were not significantly different between the two groups. Longer and larger trials are necessary to evaluate the efficacy and safety of sodium phenylbutyrate-taurursodiol in persons with ALS. (Funded by Amylyx Pharmaceuticals and others; CENTAUR ClinicaITrials.gov number, NCT03127514.) [ABSTRACT FROM AUTHOR]

The article focuses on the findings of a study that looks into the role of estrogen in treating women with urinary inconctinence (Ul). For years, estrogen has been used to treat women with Ul, but a recent study has found that hormone therapy may actuaily increase a women's risk of developing Ul, and worsen symptoms among those with the condition. Researchers randomly assigned about 27,000 postmenopausal women ages 50-79 to receive conjugated equine estrogen (0.625 mg/day) alone, estrogen (0.625 mg/day) plus the progestin medroxyprogesterone acetate (2.5 mg/day), or placebo.

The article focuses on a study concerning estrogen plus progestin which increased the risk of stroke and probable dementia in postmenopausal women in postmenopausal women. Respondents are 50 to 79 years old that underwent hormone replacement therapy (HRT). It mentions the Women's Health Initiative (WHI) hormone therapy study of estrogen plus progestin. Moreover, it notes the placebo controlled trial with a specific mean follow up period.

Abstract Precise crosstalk between the nervous and immune systems is important for neuroprotection and axon plasticity after injury. Recently, we demonstrated that IL-1β acts as a potent inducer of neurite outgrowth from organotypic brain slices in vitro, suggesting a potential function of IL-1β in axonal plasticity. Here, we have investigated the effects of IL-1β on axon plasticity during glial scar formation and on functional recovery in a mouse model of spinal cord compression injury (SCI). We used an IL-1β deficiency model (IL-1βKO mice) and administered recombinant IL-1β. In contrast to our hypothesis, the histological analysis revealed a significantly increased lesion width and a reduced number of corticospinal tract fibers caudal to the lesion center after local application of recombinant IL-1β. Consistently, the treatment significantly worsened the neurological outcome after SCI in mice compared with PBS controls. In contrast, the absence of IL-1β in IL-1βKO mice significantly improved recovery from SCI compared with wildtype mice. Histological analysis revealed a smaller lesion size, reduced lesion width and greatly decreased astrogliosis in the white matter, while the number of corticospinal tract fibers increased significantly 5 mm caudal to the lesion in IL-1βKO mice relative to controls. Our study for the first time characterizes the detrimental effects of IL-1β not only on lesion development (in terms of size and glia activation), but also on the plasticity of central nervous system axons after injury.

Abstract Pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) are considered to exert detrimental effects during brain trauma and in neurodegenerative disorders. Consistently, it has been demonstrated that IL-1β suppresses neurotrophin-mediated neuronal cell survival rendering neurons vulnerable to degeneration. Since neurotrophins are also well known to strongly influence axonal plasticity, we investigated here whether IL-1β has a similar negative impact on neurite growth. We analyzed neurite density and length of organotypic brain and spinal cord slice cultures under the influence of the neurotrophins NGF, BDNF, NT-3 and NT-4. In brain slices, only NT-3 significantly promoted neurite density and length. Surprisingly, a similar increase of neurite growth was induced by IL-1β. Additionally, both factors increased the number of brain slices displaying maximal neurite growth. Furthermore, the co-administration of IL-1β and NT-3 significantly increased the number of brain slices displaying maximal neurite growth compared to single treatments. These data indicate that these two factors synergistically stimulate two distinct aspects of neurite outgrowth, namely neurite density and neurite length from acute organotypic brain slices.

The article presents a study that examined cases of medial meniscal and subchondral cystic lesions of the medial femoral condyle in horses.

The article presents a study analyzing that hormone therapy increases incidence and severity of urinary incontinence in healthy postmenopausal women. Participants of the study included women who were 50-79 years of age and postmenopausal. Exclusion criteria of the study was breast cancer, other invasive cancer in past 10 years, venous thromboembolism, hypertriglyceridaemia, or condition with poor prognosis. Researchers concluded that in healthy postmenopausal women, hormone therapy is helpful in increasing the incidence and severity of urinary incontinence.

The article focuses on the study concerning the relationship among estrogen plus progestin use, breast cancer characteristics, and mammography recommendations. It notes the role of oestrogen plus progestogen hormone therapy (HT) in the increase of the risk of abnormal mammographic results and diagnoses of breast cancer. Details of the setting, participants, intervention, and main outcome measures of the study are presented.

Aims In a large ethnically diverse nationwide sample of post-menopausal women we explored the relationship between fasting insulin levels, ethnicity, and a wide range of anthropometric, socio-economic, and lifestyle factors. Methods Subjects were post-menopausal women aged 50–79 years without diagnosed diabetes mellitus comprising a subsample ( n = 3500) of the Women's Health Initiative (WHI) Clinical Trial and Observational Study. In a cross-sectional survey at baseline, we analysed the association between ethnicity and fasting insulin using analysis of covariance procedures and identified independent correlates of hyperinsulinaemia, defined by the 75th percentile cut point for each ethnic group. Results Fasting insulin levels were higher among African-American and Hispanic women than among non-Hispanic White or Asian women. These differences persisted after adjustment for age, educational attainment, total and central body obesity, adult weight change, family history of diabetes, smoking status, alcohol consumption, use of menopausal hormone therapy and physical activity. Higher levels of body mass index, waist–hip ratio, adult weight gain, and lower levels of total and moderate or strenuous recreational activity were independent correlates of fasting hyperinsulinaemia. Habitual walking was also inversely associated with fasting insulin. Conclusions In this cross-sectional analysis, fasting insulin levels were higher among African-American and Hispanic post-menopausal women as compared with non-Hispanic White and Asian women. In addition, obesity, adult weight gain, and low levels of moderate or strenuous physical activity were independently associated with hyperinsulinaemia. [ABSTRACT FROM AUTHOR]

The hair follicle continually undergoes dynamic remodelling in a cyclical manner involving tightly coordinated patterns of cell proliferation, differentiation and apoptosis. The oncoprotein c-Myc is a key regulator of these events in epidermal keratinocytes, but its importance in the hair growth cycle has not previously been determined.To determine the role of c-Myc in the hair growth cycle.We characterized the hair follicle phenotype of transgenic mice that permit expression of a switchable form of c-Myc (c-Myc-ER™) in the suprabasal epithelial layers of the epidermis and hair follicle.c-Myc activation increased epithelial cell proliferation in the outer root sheath and distal hair follicle, without any substantial alteration in levels of apoptosis. Moreover, chronic c-Myc activation resulted in marked desynchronization of the murine hair growth cycle, uncoupling of hair cycle-related skin thickness and enlargement of the sebaceous gland.These data implicate c-Myc in the control of hair growth cycling and hair cycle-related epidermal and sebaceous gland homeostasis. We suggest that c-Myc may be activating follicular stem cells either directly or indirectly and that this has important implications for control of the‘hair cycle clock’, hair growth and epidermal maintenance. [ABSTRACT FROM AUTHOR]

The effects of increasing aflatoxin Bi con-centration (0, 0.75, 1.5 mg/kg) on broilers with or with-out necrotic enteritis or virginiamycin were determined. In the 23-d study, 22 male Cobb 500 chicks per pen were allotted to 12 treatments (3×2×2 factorial ar-rangement) with 8 replications. Intestines of 5 birds per pen were examined for lesions on d 21. Birds were al-lowed to consume feed and water ad libitum. Aflatoxin was included in the diets from d 0. All birds received a 10x dose of coccidiosis vaccine on d 10. Pens of birds where necrotic enteritis was being induced were on Clostridium perfringens pathogen (CPP) contaminated litter from d 0. Aflatoxin decreased gain and feed intake and resulted in poorer feed:gain, increased mortality, and higher lesion scores. Inducing necrotic enteritis in-creased lesion scores and decreased feed intake and gain. Adding virginiamycin to the diets improved gain, feed intake, feed conversion, and decreased mortality. There was a 3-way interaction (aflatoxin x virginiamycin x CPP) on gain; increasing aflatoxin decreased gain and the effects of CPP and virginiamycin were dependent on aflatoxin concentration. In the absence of aflatoxin virginiamycin increased gain but was unable to prevent the growth suppression caused by CPP. At 0.75 nig/kg of aflatoxin virginiamycin no longer increased growth in non-CPP challenged birds but was able to increase growth in CPP-challenged birds. At the 1.5 mg/kg of aflatoxin concentration, virginiamycin increased gain in non-CPP-challenged birds but challenging birds with CPP had no effect on gain. Virginiamycin improved overall feed conversion with the greatest improvement at 1.5 mg/kg (aflatoxin x virginiamycin, P < 0.05). Af-latoxin increased lesion scores in unchallenged birds but not in challenged birds (aflatoxin x CPP, P < 0.001). Aflatoxin and necrotic enteritis decrease broiler perfor-mance and interact to decrease weight gain, virginia-mycin helps improve gain in challenged birds at 0.75 mg/kg of aflatoxin, but, not at 1.5 mg/kg of aflatoxin. [ABSTRACT FROM AUTHOR]

Clinical management and therapeutics development for Alzheimer's disease (AD) have entered a new era, with recent approvals of monoclonal antibody therapies targeting the underlying pathophysiology of the disease and modifying its trajectory. Imaging and fluid biomarkers are becoming increasingly important in the clinical development of AD therapeutics. This review focuses on the evidence of fluid biomarkers from recent amyloid-β-targeting clinical trials, summarizing biomarker data across 12 trials. It further proposes a simple framework to put biomarker guidance in the context of amyloid-pathway-targeted disease modification, delineates factors that impact biomarker data in clinical trials, and highlights knowledge gaps and future directions. Increased knowledge and data on biomarkers in the context of disease progression and disease modification will help to better design future AD trials and guide the clinical management of patients on AD-modifying therapies, bringing us closer to the implementation of precision medicine in AD., Competing Interests: Declaration of interests J.D. is an inventor on patents or patent applications of Eli Lilly and Company relating to the assays, methods, reagents and/or compositions of matter for p-tau assays and Aβ-targeting therapeutics. J.D. has served as a consultant or on advisory boards for Prevail Therapeutics, Eisai, Abbvie, Genotix Biotechnologies Inc., Gates Ventures, Karuna Therapeutics, AlzPath Inc., and Cognito Therapeutics, Inc. and received research support from Lilly, ADx Neurosciences, Fujirebio, AlzPath Inc., Roche Diagnostics, and Eli Lilly and Company in the past 2 years. J.D. has received speaker fees from LabCorp and Eli Lilly and Company. J.D. is a founder and advisor for Monument Biosciences. J.D. has stock or stock options in Eli Lilly and Company, Genotix Biotechnologies, AlzPath Inc., and Monument Biosciences. H.H. is an employee of Eisai and serves as reviewing editor for the Journal Alzheimer’s & Dementia. H.H. is inventor of 11 patents and has received no royalties for “In Vitro Multiparameter Determination Method for The Diagnosis and Early Diagnosis of Neurodegenerative Disorders,” patent no. 8916388; “In Vitro Procedure for Diagnosis and Early Diagnosis of Neurodegenerative Diseases,” patent no. 8298784; “Neurodegenerative Markers for Psychiatric Conditions,” publication no. 20120196300; “In Vitro Multiparameter Determination Method for The Diagnosis and Early Diagnosis of Neurodegenerative Disorders,” publication no. 20100062463; “In Vitro Method for The Diagnosis and Early Diagnosis of Neurodegenerative Disorders,” publication no. 20100035286; “In Vitro Procedure for Diagnosis and Early Diagnosis of Neurodegenerative Diseases,” publication no. 20090263822; “In Vitro Method for The Diagnosis of Neurodegenerative Diseases,” patent no. 7547553; “CSF Diagnostic in Vitro Method for Diagnosis of Dementias and Neuroinflammatory Diseases,” publication no. 20080206797; “In Vitro Method for The Diagnosis of Neurodegenerative Diseases,” publication no. 20080199966; “Neurodegenerative Markers for Psychiatric Conditions,” publication no. 20080131921; “Method for Diagnosis of Dementias and Neuroinflammatory Diseases Based on an Increased Level of Procalcitonin in Cerebrospinal Fluid,” US patent no. 10921330. O.H. has acquired research support (for the institution) from AVID Radiopharmaceuticals, Biogen, C2N Diagnostics, Eli Lilly, Eisai, Fujirebio, GE Healthcare, and Roche. In the past 2 years, he has received consultancy/speaker fees from AC Immune, Alzpath, BioArctic, Biogen, Bristol Meyer Squibb, Cerveau, Eisai, Eli Lilly, Fujirebio, Merck, Novartis, Novo Nordisk, Roche, Sanofi, and Siemens. S.H. is an owner and employee of Pentara Corporation, a company that consults with dozens of companies in the Alzheimer’s space, including Biogen. No consulting fees were paid for work on this publication. Y.H., M.C., and P.S. are employees of Eisai., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Sodium phenylbutyrate and taurursodiol (PB and TURSO) is hypothesized to mitigate endoplasmic reticulum stress and mitochondrial dysfunction, two of many mechanisms implicated in Alzheimer's disease (AD) pathophysiology., Methods: The first-in-indication phase 2a PEGASUS trial was designed to gain insight into PB and TURSO effects on mechanistic targets of engagement and disease biology in AD. The primary clinical efficacy outcome was a global statistical test combining three endpoints relevant to disease trajectory (cognition [Mild/Moderate Alzheimer's Disease Composite Score], function [Functional Activities Questionnaire], and total hippocampal volume on magnetic resonance imaging). Secondary clinical outcomes included various cognitive, functional, and neuropsychiatric assessments. Cerebrospinal fluid (CSF) biomarkers spanning multiple pathophysiological pathways in AD were evaluated in participants with both baseline and Week 24 samples (exploratory outcome)., Results: PEGASUS enrolled 95 participants (intent-to-treat [ITT] cohort); cognitive assessments indicated significantly greater baseline cognitive impairment in the PB and TURSO ( n  = 51) versus placebo ( n  = 44) group. Clinical efficacy outcomes did not significantly differ between treatment groups in the ITT cohort. CSF interleukin-15 increased from baseline to Week 24 within the placebo group ( n  = 34). In the PB and TURSO group ( n  = 33), reductions were observed in core AD biomarkers phosphorylated tau-181 (p-tau181) and total tau; synaptic and neuronal degeneration biomarkers neurogranin and fatty acid binding protein-3 (FABP3); and gliosis biomarker chitinase 3-like protein 1 (YKL-40), while the oxidative stress marker 8-hydroxy-2-deoxyguanosine (8-OHdG) increased. Between-group differences were observed for the Aβ42/40 ratio, p-tau181, total tau, neurogranin, FABP3, YKL-40, interleukin-15, and 8-OHdG. Additional neurodegeneration, inflammation, and metabolic biomarkers showed no differences between groups., Discussion: While between-group differences in clinical outcomes were not observed, most likely due to the small sample size and relatively short treatment duration, exploratory biomarker analyses suggested that PB and TURSO engages multiple pathophysiologic pathways in AD., Highlights: Proteostasis and mitochondrial stress play key roles in Alzheimer's disease (AD).Sodium phenylbutyrate and taurursodiol (PB and TURSO) targets these mechanisms.The PEGASUS trial was designed to assess PB and TURSO effects on biologic AD targets.PB and TURSO reduced exploratory biomarkers of AD and neurodegeneration.Supports further clinical development of PB and TURSO in neurodegenerative diseases., Competing Interests: S.E.A. was the principal investigator of the PEGASUS trial and contributed to its design, conduct, statistical analyses of the exploratory biomarker assessments, writing and revision of this manuscript. S.E.A. reported receiving institutional grant or sponsored research support from the Alzheimer's Association, Alzheimer Drug Discovery Foundation, Challenger Foundation, John Sperling Foundation, National Institutes of Health, Prion Alliance, AbbVie Inc, AC Immune SA, Amylyx, Athira Pharma Inc, ChromaDex Inc, Cyclerion Therapeutics Inc, EIP Pharma Inc, Janssen Pharmaceutical/Johnson & Johnson, Ionis Pharmaceuticals, Novartis AG, Seer Bioscience Inc, vTv Therapeutics; honoraria for lectures from AbbVie Inc, Biogen Inc, and Eisai Co Ltd; payments for participation on scientific advisory boards of Allyx Therapeutics Inc, Bob's Last Marathon, Quince Therapeutics/Cortexyme Inc, Jocasta Neuroscience, and Sage Therapeutics Inc; consulting fees from Cognito Therapeutics Inc, Cassava Sciences, EIP Pharma Inc, M3 Biotechnology Inc, Orthogonal Neuroscience Inc, Risen Pharmaceutical Technology. S.H. is an employee and owner of Pentara Corporation, which was contracted to perform statistical analyses for the PEGASUS trial, including the clinical efficacy outcomes analyses described in this manuscript; reports consulting fees paid to Pentara from multiple pharmaceutical companies developing therapies for neurodegenerative diseases; and reports data safety monitoring board or advisory board fees from Alzheon, Eisai, and Prothena Biosciences paid to Pentara. J.N.‐J. and N.K. are employees of Pentara Corporation. V.J.W. reports consulting fees from Cognito Therapeutics, unrelated to the present manuscript, and an unpaid scientific advisory committee position in Division 40 of the American Psychological Association. J.M.B. reports clinical trial support from the National Institutes of Health, Eli Lilly, Biogen, AbbVie, AstraZeneca, and Roche, unrelated to the manuscript, and consulting fees from Amylyx Pharmaceuticals, Renew Research, Eisai, Eli Lilly, and Labcorp. M.C. reports grants from the American College of Radiology, the Alzheimer's Association, Novo Nordisk, Avanir Pharmaceuticals, Biogen, and the National Institutes of Health, all paid to the Tennessee Memory Disorders Foundation, and is an Alzheimer's Tennessee Board of Directors and Tennessee Memory Disorders Foundation volunteer. A.J.M. reports advisory board fees from Amylyx Pharmaceuticals and honoraria from the Alzheimer's Association Speaker's Bureau. S.N.V. reports grants to his affiliated institution from Biogen, Eisai, and Eli Lilly and participation on a data safety monitoring board or advisory board for Eli Lilly and Alector Therapeutics. Z.A. receives research support from the National Institutes of Health, Amylyx Pharmaceuticals, and Eli Lilly to her affiliated academic institution; lecture honoraria from Spire Learning and Summus; payment for expert testimony from the city of Naperville (government); support for attending professional society meetings from National Institutes of Health funds and academic institutions of higher learning; advisory board fees and consulting for non‐for‐profit (California Institute for Regenerative Medicine; international governmental funding agencies) and for‐profit organizations (including Eisai, Inc; Summus); and is a Specialty Chief Editor for Frontiers in Neurology. J.N. was the principal investigator for the Icahn School of Medicine at Mount Sinai (MSSM) PEGASUS trial site but was not compensated in this role; is a co‐director of the MSSM Alzheimer's Disease Research Center Outreach, Recruitment, and Engagement and Clinical Cores; and is editor of Focus on Healthy Aging. K.B. reports clinical trial support from Eisai and the Alzheimer's Clinical Trials Consortium, unrelated to this work, and fees for data monitoring committee participation from Eli Lilly. B.C.C. reports grants from the National Institutes of Health, Challenger Foundation, Bright Focus Foundation, Alzheimer's Research UK, and Ono Pharmaceutical to her affiliated institution; reports conference attendance support from Alzheimer's Research UK; and is an Academic Coordinator for the Alzheimer's Research UK Thames Valley Network. H.H.D. contributed to the statistical analyses in Table S4 of the exploratory biomarker assessments described in this manuscript and reports consulting fees from ALZpath and Biogen. R.E.T. is a paid consultant and shareholder in Amylyx Pharmaceuticals and was involved with the PEGASUS trial design and analyzing de‐identified trial results following the completion of the trial but not with the execution of the trial. P.D.Y. is the Chief Medical Officer and has stock and stock option ownership in Amylyx Pharmaceuticals. K.L. was an employee of Amylyx Pharmaceuticals from July 2015 through August 2021 and received stock options while employed with Amylyx Pharmaceuticals. B.A.T. and P.K. have no disclosures to report. Author disclosures are available in the Supporting Information., (© 2024 Amylyx Pharmaceuticals. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)