Biomarkers.

Background: Phosphorylated tau (p-tau) 181 was isolated in aqueous humor and was correlated with other measures that might be consistent with Alzheimer's disease (AD) including higher plasma p-tau181 concentrations and lower Montreal Cognitive Assessment (MoCA blind version 7.1) scores.

Method: Blood samples, aqueous humor samples, and MoCA scores were collected from patients at the time of cataract surgery.

Biomarkers.

Background: Older adults with dual cognitive and mobility impairments have higher financial costs and poorer quality of life than adults with either impairment alone. Blood biomarkers of Alzheimer Disease (AD) pathology (Aβ42, Aβ40 and p-tau181) and neurodegeneration (neurofilament light (NFL) and glial fibrillary acidic protein (GFAP)) may identify individuals at risk for both mobility and cognitive impairment and provide novel insights into mechanistic underpinnings.

Method: Blood biomarkers (SiMoA Quanterix N4PE, p-tau181 single-plex) were available in a subsample of 1751 ARIC study participants at Visit 5 (V5, 2011-13, mean age 76.

Biomarkers.

Background: Subjective cognitive decline (SCD), or a person's perception of changes in their cognitive abilities, has been identified as a possible early marker of preclinical Alzheimer's disease (AD) in non-Hispanic Whites; however, research is lacking about the clinical utility of SCD in diverse populations. This study investigated the associations of self and informant reports of SCD, plasma biomarker profiles of AD, and objective cognitive performance in Hispanic older adults living in Miami.

Method: Hispanic participants enrolled in the 1Florida Alzheimer's Disease Research Center who completed neuropsychological testing and blood draws for biomarker analysis were eligible.

Biomarkers.

Background: Dys-connectivity has been repeatedly shown in Alzheimer's Disease (AD) but the change of connectivity gradient across the brain is under-studied. In this study, we used resting state fMRI (rsfMRI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to build a whole brain functional connectivity matrix. We then compared the major connectivity gradients decomposed from the connectivity matrix from normal controls (NC), mild cognitive impairment (MCI), and AD patients.

Biomarkers.

Background: Aging is the strongest risk factor for Alzheimer's disease (AD). Accordingly, identifying biomarkers of accelerated aging is a major focus of AD prevention research. Current MRI-based "aging clocks" (i.

Biomarkers.

Background: The Parkinson's disease (PD) cognition-related covariance pattern (PDCP) was derived from network analysis of metabolic positron emission tomography (PET). The expression score is a feasible imaging biomarker that correlates with neuropsychological test performance. Graph analysis within specific networks characterizes brain function, particularly in terms of assortativity, which reflects the tendency to connect to nodes with similar degree values.

Biomarkers.

Background: Cognitively unimpaired (CU) older adults with abnormal levels of β-amyloid (Aβ) deposition are considered in the preclinical stage of Alzheimer's disease (AD) and, when combined with the subjective cognitive decline (SCD), are proposed as the stage 2 AD in the NIA-AA framework. Here, we aim to investigate whether neuropathologic deterioration increases in early stages, particularly in stage 2 AD.

Method: We included 341 CU participants over 50 years of age from the Sino Longitudinal Study on Cognitive Decline (SILCODE) study.

Biomarkers.

Background: Amyloid-b deposition and tau tangle formation are the key pathologies of Alzheimer's disease (AD). The presence of these pathologies in cerebrospinal fluid (CSF) biomarkers is used for a biological diagnosis of AD. It remains unclear how the prevalence of AT biomarker profiles depends on apolipoprotein E (APOE) genotype.

Biomarkers.

Background: Worse sleep is associated with a greater risk of Alzheimer's disease (AD). However, few studies have linked objective sleep with neuroimaging outcomes, limiting our understanding of how poor sleep impacts the brain. The U.

Biomarkers.

Background: Since 2012, many groups have been using immunomagnetic reduction (IMR) for assaying plasma amyloid β 1-40 (Aβ) peptide, Aβ peptide and total tau protein (T-Tau) in cognitively normal controls (NC) and patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease dementia (ADD). Tremendous results have been independently reported. In this work, we summarize the reported levels of plasma Aβ, Aβ and T-Tau to investigate the consistence among studies.

Biomarkers.

Background: Metabolomics captures net influences of exposome, diet, gut microbiome, and genome, informing about individuality and how we respond to interventions. Applications of metabolomics in pharmacology are starting to enable a Systems Pharmacology approach, where the outcome of a treatment is considered to evolve from effects on complex molecular networks, enabling insights into response variations. We bring the power of these approaches to the study of the MIND, a Mediterranean DASH diet for prevention of cognitive decline.

Biomarkers.

Background: The G protein-coupled receptor GPR39 is heavily associated with the pathogenesis of neurologic disorders, including Alzheimer's disease (AD) and related dementia (ADRD). Its dysregulation of zinc 2+ (Zn) processes triggers metallic dyshomeostasis, oxidative stress, neuroinflammation, microtubule destabilization, synaptic dysfunction, and tau phosphorylation-all hallmarks of neurodegeneration. Hence, pharmacologic modulation of GPR39 could offer an effective treatment against AD and ADRD.

Biomarkers.

Background: Detecting functional performance decline from normal aging to dementia is critical for early detection and intervention. The informant-based A-IADL-Q-SV has been demonstrated with good psychometric properties. The aims of this study were to: (1) translate, culturally adapt, and validate the Traditional Chinese version of the A-IADL-Q-SV-TC for Taiwanese; (2) evaluate the psychometric properties.

Biomarkers.

Background: The aim of this study was to identify a gut microbial signature associated with patterns of gray matter volume in AD, and to validate the microbial signature by testing it against measures of AD pathology and cognitive performance. Prior literature suggests that microbial species involved in bile acid production and inflammation may be implicated in the microbial signature.

Method: The sample comprised 204 Microbiome in Alzheimer's Risk Study participants (22 AD, 10 MCI, and 172 CN; 129 Females, 78 APOE+) from the Wisconsin Alzheimer's Disease Research Center and Wisconsin Registry for Alzheimer's Prevention.

Biomarkers.

Background: Increasingly, research participants in Alzheimer's studies are seeking disclosure of research results. However, there are no guidelines for result disclosure and specifically, few studies report on their biomarker disclosure procedure. The Duke/UNC ADRC seeks to disclose research results to participants in a standardized fashion with high participant satisfaction.

Biomarkers.

Background: There is limited information on biomarker-defined Alzheimer's disease (AD) pathology in community-recruited individuals of diverse racial and ethnic groups. Here, we assessed the association of race/ethnicity with baseline biomarkers and cognitive measures and hypothesized a lower impact of AD pathology in non-Hispanic White (nHW) participants in the U.S.

Biomarkers.

Background: While we do not yet have the means to detect early Alzheimer's disease (AD), studying subjects at risk conferred by the presence of the APOE4 allele, can provide useful information before clinical onset. We show that using symmetric bilinear regression with L1 penalty (SBL) of individual (DTI, fMRI) and fused connectomes, we can identify vulnerable regions changing in association with hallmark AD biomarkers measured in cerebrospinal fluid: amyloid beta Aβ42/40, phosphorylated tau (PTAU), and neurofibrillary light (NfL) as a proxy for neurodegeneration.

Methods: We use structural connectomes derived from diffusion-weighted MRI (DTI) and functional connectomes (fMRI) from 57 subjects, 45 normal controls and 12 cognitively impaired to predict CSF Aβ42/40, PTAU, and NfL to reflect neurodegeneration.

Biomarkers.

Background: Alzheimer's disease neuropathologic change (AD-NC) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) are common in older adults and have been associated with brain atrophy, cognitive decline, and dementia. Since AD-NC and LATE-NC are often comorbid and due to the fact that LATE-NC can only be detected at autopsy, in this work, we combined deformation-based morphometry (DBM) on ex-vivo brain MRI and detailed neuropathological evaluation in a large number of community-based older adults to investigate the difference in brain atrophy patterns associated with AD-NC and LATE-NC.

Method: Cerebral hemispheres from 912 older adults participating in four longitudinal, clinical-pathologic cohort studies of aging were included in this work: MAP, ROS, MARS, and AA Core of the Rush Alzheimer's Disease Research Center (Rush ADRC) (Figure 1).

Biomarkers.

Background: Understanding the relationship between AβPET and AβCSF biomarkers will define their potential utility in Aβ treatment. Few longitudinal or neuropathological comparisons have been reported. We assessed the relationship of AβPET and AβCSF biomarkers in a large community cohort.

Biomarkers.

Background: Blood plasma metrics provide excellent biomarkers of the presence of Alzheimer's disease (AD) pathology in population cohorts. However, it is less clear whether plasma metrics correlate with PET measures of AD pathology in cohorts of patients with advanced AD disease, particularly in those with atypical clinical presentations of AD.

Method: Seventy-seven patients (visual variant=43, language variant=32, motor variant=1 and dysexecutive variant=1) with PET biomarker-confirmed atypical AD were recruited by the Neurodegenerative Research group at Mayo Clinic, Rochester, MN, underwent Aβ (Pittsburgh Compound-B) and tau (F-flortaucipir) PET and provided a blood sample.

Biomarkers.

Background: Residence in a disadvantaged neighborhood (e.g., high poverty rate, poor housing, etc.

Biomarkers.

Background: While Alzheimer disease (AD) is the most common cause of dementia, it has long been recognized that cardiovascular and cerebrovascular health plays a major role in cognitive function. As such, the development of accessible biomarkers to assess vascular cognitive impairment and dementia (VCID) is a key step towards identifying effective prevention and treatment strategies. While a set of blood-based VCID biomarkers has been under investigation, there is a critical paucity of data from genetically admixed individuals.

Biomarkers.

Background: Quantitative transport mapping (QTM) has been developed for estimation of blood flow velocity with 4D dynamic tracer concentration data (Zhou et. al., Magn.

Biomarkers.

Background: While we know dementia in Alzheimer's disease (AD) results from the accumulation of β-amyloid (Aβ), tau pathology, and hippocampus atrophy (HC), it is still unclear how these factors impose cognitive decline.

Method: We used Structural Equation Models (SEM; lavaan R package) to explore the complex relationships between the neurobiological factors in the early stages preceding AD dementia in the TRIAD cohort. Our sample comprised 333 timepoints of neuropsychological evaluation (MoCA), structural MRI, Aβ ([18F]AZD4694), and tau ([18F]MK6240) PET of cognitively healthy (NC) and mild cognitive impaired (MCI) participants.

Biomarkers.

Background: Our Alzheimer Disease Metabolomics Consortium (ADMC), part of the Accelerating Medicines Partnership for AD (AMP-AD) and in partnership with AD Neuroimaging Initiative (ADNI), applied state-of-the-art metabolomics and lipidomics technologies combined with genomic and imaging data to map metabolic failures across the trajectory of the disease. Our studies confirmed that peripheral metabolic changes influenced by the exposome inform about cognitive changes, brain imaging changes, and ATN markers for disease confirming that peripheral and central changes are connected, in part through the metabolome.

Methods: To map the biochemical changes in AD, we used various targeted and untargeted metabolic platforms to profile ∼800 postmortem brain tissue, and ∼ 5000 blood samples.