Plasma and neuroimaging biomarkers of small vessel disease and Alzheimer's disease in a diverse cohort: MESA.

Introduction: Little is known about how Alzheimer's disease (AD) plasma biomarkers relate to cerebral small vessel disease (cSVD) neuroimaging biomarkers.

Methods: The study involved 251 Wake Forest Multi-Ethnic Study of Atherosclerosis (MESA) Exam 6 participants with plasma AD biomarkers, MRI, amyloid PET, and adjudicated cognitive status. Multivariable models examined cross-sectional relationships between plasma and neuroimaging biomarkers, considering comorbidities.

Evaluation of plasma p-tau217 for detecting amyloid pathology in a diverse and heterogeneous community-based cohort.

Introduction: Studies suggest excellent performance of plasma p-tau217 for detecting amyloid pathology, though studies in more diverse populations are needed to validate previously determined cutpoints.

Methods: Plasma p-tau217 utility for detecting amyloid pathology (Aβ) via amyloid PET (=598) and/or cerebrospinal fluid (CSF; =154) was assessed in a heterogeneous, community-based cohort in the Wake Forest Alzheimer's Disease Research Center (WFADRC). Participants (=598) were 21% Black; 313 cognitive unimpaired (CU), 214 mild cognitive impairment (MCI), and 64 dementia (DEM); 49% prediabetic, 44% hypertensive; 29% overweight/obese; and 64% with mild-to-moderate kidney disease.

Associations among plasma, MRI, and amyloid PET biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities in a community-dwelling cohort.

Introduction: We evaluated associations between plasma and neuroimaging-derived biomarkers of Alzheimer's disease and related dementias and the impact of health-related comorbidities.

Methods: We examined plasma biomarkers (neurofilament light chain, glial fibrillary acidic protein, amyloid beta [Aβ] 42/40, phosphorylated tau 181) and neuroimaging measures of amyloid deposition (Aβ-positron emission tomography [PET]), total brain volume, white matter hyperintensity volume, diffusion-weighted fractional anisotropy, and neurite orientation dispersion and density imaging free water. Participants were adjudicated as cognitively unimpaired (CU; N = 299), mild cognitive impairment (MCI; N = 192), or dementia (DEM; N = 65).

The interactive effects of psychosocial stress and diet composition on health in primates.

Social disadvantage and diet composition independently impact myriad dimensions of health. They are closely entwined, as social disadvantage often yields poor diet quality, and may interact to fuel differential health outcomes. This paper reviews effects of psychosocial stress and diet composition on health in nonhuman primates and their implications for aging and human health.

Plasma Neurofilament Light Chain Levels Are Elevated in Children and Young Adults With Wolfram Syndrome.

Wolfram syndrome is a rare disease caused by pathogenic variants in the gene with progressive neurodegeneration. As an easily accessible biomarker of progression of neurodegeneration has not yet been found, accurate tracking of the neurodegenerative process over time requires assessment by costly and time-consuming clinical measures and brain magnetic resonance imaging (MRI). A blood-based measure of neurodegeneration, neurofilament light chain (NfL), is relatively inexpensive and can be repeatedly measured at remote sites, standardized, and measured in individuals with MRI contraindications.

Cognitively normal APOE ε4 carriers have specific elevation of CSF SNAP-25.

Cerebrospinal fluid (CSF) synaptosomal-associated protein 25 (SNAP-25) and neurogranin (Ng) are recently described biomarkers for pre- and postsynaptic integrity known to be elevated in symptomatic Alzheimer disease (AD). Their relationship with Apolipoprotein E (APOE) ε4 carrier status, the major genetic risk factor for AD, remains unclear. In this study, CSF SNAP-25 and Ng were compared in cognitively normal APOE ε4 carriers and noncarriers (n = 274, mean age 65 ± 9.

Quantification of white matter cellularity and damage in preclinical and early symptomatic Alzheimer's disease.

Interest in understanding the roles of white matter (WM) inflammation and damage in the pathophysiology of Alzheimer disease (AD) has been growing significantly in recent years. However, in vivo magnetic resonance imaging (MRI) techniques for imaging inflammation are still lacking. An advanced diffusion-based MRI method, neuro-inflammation imaging (NII), has been developed to clinically image and quantify WM inflammation and damage in AD.

Longitudinal decreases in multiple cerebrospinal fluid biomarkers of neuronal injury in symptomatic late onset Alzheimer's disease.

Introduction: Individuals in early stages of Alzheimer's disease are a targeted population for secondary prevention trials aimed at preserving normal cognition. Understanding within-person biomarker(s) change over time is critical for trial enrollment and design.

Methods: Longitudinal cerebrospinal fluid samples from the Alzheimer's Disease Neuroimaging Initiative were assayed for novel markers of neuronal/synaptic injury (visinin-like protein 1, Ng, and SNAP-25) and neuroinflammation (YKL-40) and compared with β amyloid 42, tau, and phospho-tau181.

Upward drift in cerebrospinal fluid amyloid β 42 assay values for more than 10 years.

Introduction: The best-established cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease are levels of amyloid β 42 (Aβ42), total tau (tau), and phosphorylated tau 181 (ptau). We examined whether a widely used commercial immunoassay for CSF Aβ42, tau, and ptau provided stable measurements for more than ∼10 years.

Methods: INNOTEST assay values for CSF Aβ42, tau, and ptau from Washington University in St.

Chitinase-3-like 1 protein (CHI3L1) locus influences cerebrospinal fluid levels of YKL-40.

Background: Alzheimer's disease (AD) pathology appears several years before clinical symptoms, so identifying ways to detect individuals in the preclinical stage is imperative. The cerebrospinal fluid (CSF) Tau/Aβ ratio is currently the best known predictor of AD status and cognitive decline, and the ratio of CSF levels of chitinase-3-like 1 protein (CHI3L1, YKL-40) and amyloid beta (Aβ) were reported as predictive, but individual variability and group overlap inhibits their utility for individual diagnosis making it necessary to find ways to improve sensitivity of these biomarkers.

Methods: We used linear regression to identify genetic loci associated with CSF YKL-40 levels in 379 individuals (80 cognitively impaired and 299 cognitively normal) from the Charles F and Joanne Knight Alzheimer's Disease Research Center.

Obstructive sleep apnea decreases central nervous system-derived proteins in the cerebrospinal fluid.

We hypothesized that one mechanism underlying the association between obstructive sleep apnea (OSA) and Alzheimer's disease is OSA leading to decreased slow wave activity (SWA), increased synaptic activity, decreased glymphatic clearance, and increased amyloid-β. Polysomnography and lumbar puncture were performed in OSA and control groups. SWA negatively correlated with cerebrospinal fluid (CSF) amyloid-β-40 among controls and was decreased in the OSA group.

Longitudinal relationships among biomarkers for Alzheimer disease in the Adult Children Study.

Objective: To determine whether and how longitudinal rates of change in MRI volumetrics, CSF concentrations of Alzheimer-related proteins, molecular imaging of cerebral fibrillar amyloid with PET using the [(11)C] benzothiazole tracer, Pittsburgh compound B (PiB), and cognition were associated among asymptomatic middle-aged to older individuals.

Methods: Multivariate mixed models for repeated measures were used to assess the correlations on the rates of changes across markers.

Results: Among 209 asymptomatic middle-aged to older individuals longitudinally followed for up to 11 years (mean 6.

Longitudinal Cerebrospinal Fluid Biomarker Changes in Preclinical Alzheimer Disease During Middle Age.

Importance: Individuals in the presymptomatic stage of Alzheimer disease (AD) are increasingly being targeted for AD secondary prevention trials. How early during the normal life span underlying AD pathologies begin to develop, their patterns of change over time, and their relationship with future cognitive decline remain to be determined.

Objective: To characterize the within-person trajectories of cerebrospinal fluid (CSF) biomarkers of AD over time and their association with changes in brain amyloid deposition and cognitive decline in cognitively normal middle-aged individuals.

Hyperglycemia modulates extracellular amyloid-β concentrations and neuronal activity in vivo.

Epidemiological studies show that patients with type 2 diabetes (T2DM) and individuals with a diabetes-independent elevation in blood glucose have an increased risk for developing dementia, specifically dementia due to Alzheimer's disease (AD). These observations suggest that abnormal glucose metabolism likely plays a role in some aspects of AD pathogenesis, leading us to investigate the link between aberrant glucose metabolism, T2DM, and AD in murine models. Here, we combined two techniques – glucose clamps and in vivo microdialysis – as a means to dynamically modulate blood glucose levels in awake, freely moving mice while measuring real-time changes in amyloid-β (Aβ), glucose, and lactate within the hippocampal interstitial fluid (ISF).

Progress update: fluid and imaging biomarkers in Alzheimer's disease.

Alzheimer's disease (AD) is a growing health crisis around the world. Although significant progress has been made in our understanding of AD pathogenesis, there is currently no effective treatment to delay onset or prevent the disease. The focus has now shifted to the identification and treatment of AD in the early clinical stages as well as before cognitive symptoms emerge-during the long preclinical stage.

Amyloid imaging and CSF biomarkers in predicting cognitive impairment up to 7.5 years later.

Objectives: We compared the ability of molecular biomarkers for Alzheimer disease (AD), including amyloid imaging and CSF biomarkers (Aβ42, tau, ptau181, tau/Aβ42, ptau181/Aβ42), to predict time to incident cognitive impairment among cognitively normal adults aged 45 to 88 years and followed for up to 7.5 years.

Methods: Longitudinal data from Knight Alzheimer's Disease Research Center participants (N = 201) followed for a mean of 3.