Disentangling relationships between Alzheimer's disease plasma biomarkers and established biomarkers in patients of tertiary memory clinics.

Background: Several plasma biomarkers for Alzheimer's disease (AD) have demonstrated diagnostic and analytical robustness. Yet, contradictory results have been obtained regarding their association with standard diagnostic markers of AD. This study aims to investigate the specific relationship between the AD biomarkers currently used in clinical practice and the plasma biomarkers.

Neuroinflammation, cerebrovascular dysfunction and diurnal cortisol biomarkers in a memory clinic cohort: Findings from the Co-STAR study.

Cortisol dysregulation, neuroinflammation, and cerebrovascular dysfunction are biological processes that have been separately shown to be affected in Alzheimer's disease (AD). Here, we aimed to identify biomarker signatures reflecting these pathways in 108 memory clinic patients with subjective cognitive decline (SCD, N = 40), mild cognitive impairment (MCI, N = 39), and AD (N = 29). Participants were from the well-characterized Cortisol and Stress in Alzheimer's Disease (Co-STAR) cohort, recruited at Karolinska University Hospital.

Brain amyloid load, subjective memory complaints, and cognitive trajectories in older individuals at risk for dementia.

Background And Purpose: This study evaluated associations of brain amyloid with 2-year objective and subjective cognitive measures in a trial-ready older general population at risk for dementia.

Methods: Forty-eight participants in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability underwent C-Pittsburgh compound B (PiB) positron emission tomography (PET) scans and assessment of cognition (modified Neuropsychological Test Battery [NTB]) and subjective memory complaints (Prospective and Retrospective Memory Questionnaire).

Results: Mean age was 71.

Assessment of brain-derived extracellular vesicle enrichment for blood biomarker analysis in age-related neurodegenerative diseases: An international overview.

Introduction: Brain-derived extracellular vesicles (BEVs) in blood allows for minimally-invasive investigations of central nervous system (CNS) -specific markers of age-related neurodegenerative diseases (NDDs). Polymer-based EV- and immunoprecipitation (IP)-based BEV-enrichment protocols from blood have gained popularity. We systematically investigated protocol consistency across studies, and determined CNS-specificity of proteins associated with these protocols.

DEAD Box Helicase 24 Is Increased in the Brain in Alzheimer's Disease and Mice and Influences Presymptomatic Pathology.

At the time of diagnosis, Alzheimer's disease (AD) patients already suffer from significant neuronal loss. The identification of proteins that influence disease progression before the onset of symptoms is thus an essential part of the development of new effective drugs and biomarkers. Here, we used an unbiased O labelling proteomics approach to identify proteins showing altered levels in the AD brain.

Diurnal cortisol, neuroinflammation, and neuroimaging visual rating scales in memory clinic patients.

Background: Neuroinflammation is a hallmark of the Alzheimer's disease (AD) pathogenic process. Cortisol dysregulation may increase AD risk and is related to brain atrophy. This cross-sectional study aims to examine interactions of cortisol patterns and neuroinflammation markers in their association with neuroimaging correlates.

CSF protein ratios with enhanced potential to reflect Alzheimer's disease pathology and neurodegeneration.

Background: Amyloid and tau aggregates are considered to cause neurodegeneration and consequently cognitive decline in individuals with Alzheimer's disease (AD). Here, we explore the potential of cerebrospinal fluid (CSF) proteins to reflect AD pathology and cognitive decline, aiming to identify potential biomarkers for monitoring outcomes of disease-modifying therapies targeting these aggregates.

Method: We used a multiplex antibody-based suspension bead array to measure the levels of 49 proteins in CSF from the Swedish GEDOC memory clinic cohort at the Karolinska University Hospital.

CYP46A1-mediated cholesterol turnover induces sex-specific changes in cognition and counteracts memory loss in ovariectomized mice.

The brain-specific enzyme CYP46A1 controls cholesterol turnover by converting cholesterol into 24-hydroxycholesterol (24OH). Dysregulation of brain cholesterol turnover and reduced levels are observed in Alzheimer's disease (AD). In this study, we report that overexpression in aged female mice leads to enhanced estrogen signaling in the hippocampus and improved cognitive functions.

Assessment of brain-derived extracellular vesicle enrichment for blood biomarker analysis in age-related neurodegenerative diseases: An international overview.

Introduction: Brain-derived extracellular vesicles (BEVs) in blood allows for minimally- invasive investigations of CNS-specific markers of age-related neurodegenerative diseases (NDDs). Polymer-based EV- and immunoprecipitation (IP)-based BEV-enrichment protocols from blood have gained popularity. We systematically investigated protocol consistency across studies, and determined CNS-specificity of proteins associated with these protocols.

APOE-Genotype and Insulin Modulate Estimated Effect of Dietary Macronutrients on Cognitive Performance: Panel Analyses in Nondiabetic Older Adults at Risk of Dementia.

Background: The apolipoprotein E gene (APOE ε-2/3/4, combined as 6 different genotypes: ε-22/23/24/33/34/44) and insulin status modulate dementia risk and play a role in the metabolism of macronutrients.

Objectives: We aimed to examine APOE-genotype and fasting insulin as effect modifiers of the slopes between dietary macronutrients and cognitive performance among older adults at risk of dementia.

Methods: Panel analyses-with diet and cognition measured at baseline and follow-up at years 1 and 2-were performed in a sub-sample from the FINGER (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) trial (n = 676, 60-77 y, 46% females, all nondiabetics).

SIRT2 Inhibition Rescues Neurodegenerative Pathology but Increases Systemic Inflammation in a Transgenic Mouse Model of Alzheimer's Disease.

Sirtuin 2 (SIRT2) has been proposed to have a central role on aging, inflammation, cancer and neurodegenerative diseases; however, its specific function remains controversial. Recent studies propose SIRT2 pharmacological inhibition as a therapeutic strategy for several neurodegenerative diseases including Alzheimer's disease (AD). Surprisingly, none of these published studies regarding the potential interest of SIRT2 inhibition has assessed the peripheral adverse side consequences of this treatment.

Alzheimer's disease biomarker profiling in a memory clinic cohort without common comorbidities.

Alzheimer's disease is a multifactorial disorder with large heterogeneity. Comorbidities such as hypertension, hypercholesterolaemia and diabetes are known contributors to disease progression. However, less is known about their mechanistic contribution to Alzheimer's pathology and neurodegeneration.

Profiling of plasma biomarkers in the context of memory assessment in a tertiary memory clinic.

Plasma biomarkers have shown promising performance in research cohorts in discriminating between different stages of Alzheimer's disease (AD). Studies in clinical populations are necessary to provide insights on the clinical utility of plasma biomarkers before their implementation in real-world settings. Here we investigated plasma biomarkers (glial fibrillary acidic protein (GFAP), tau phosphorylated at 181 and 231 (pTau181, pTau231), amyloid β (Aβ) 42/40 ratio, neurofilament light) in 126 patients (age = 65 ± 8) who were admitted to the Clinic for Cognitive Disorders, at Karolinska University Hospital.