Establishing tau-PET cut-points for cognitive diagnosis with F-PI-2620 in a multi-ethnoracial cohort.

F-PI-2620 is a newer tau-PET tracer with minimal off-target binding in thechoroid plexus. Defining tau cut-points to differentiate between cognitively unimpaired andimpaired individuals is crucial for both biomarker validation and clinical use, but researchusingF-PI-2620 is limited. In 675 participants (mean age: 64, 64% Female, 186Hispanic, 209 non-Hispanic Black, and 280 non-Hispanic White) from the Health and Aging BrainStudy-Health Disparities, we used the area under the receiver operating characteristic curve toidentify a region of interest and corresponding cut-point at whichF-PI-2620standardized uptake value ratio best distinguished between amyloid negative cognitivelyunimpaired and amyloid-positive cognitively-impaired individuals.

Plasma brain-derived tau: analytical and clinical validation of the first commercial immunoassay.

Background: Brain-derived tau (BD-tau) is a promising blood-based biomarker for neurodegeneration/brain injury in neurodegenerative and acute neurological disorders. However, widespread use is hampered by lack of commercial assays. We evaluated the analytical and clinical validity of the first commercial research use only BD-tau assay - the Quanterix BD-tau Advantage PLUS.

Comparison of visual and analytic methods of Alzheimer's disease pathologic staging.

Introduction: Methods for standardizing positron emission tomography (PET) indices of β-amyloid (Aβ) (Centiloid [CL]) and tau (CenTauRz, CTRz) burden facilitates direct comparisons across radiotracers and supports in vivo biologic staging per the AT(N) (Aβ [A], tau [T], and neurodegeneration [N]) framework. In lieu of post mortem examination, visual interpretation is the most sensitive indicator of these pathologies. Here, we compared the performance of analytic and visual methods of AT(N) staging.

Plasma biomarkers identify brain ATN abnormalities in a dementia-free population-based cohort.

Introduction: Using the ATN framework, we evaluated the potential of plasma biomarkers to identify abnormal brain amyloid-beta (Aβ) positron emission tomography (PET), tau-PET and neurodegeneration in a socioeconomically disadvantaged population-based cohort.

Methods: Community-dwelling dementia-free (n = 113, including 102 (91%) cognitively normal) participants underwent ATN neuroimaging and plasma biomarker assessments.

Results: Plasma Aβ42/Aβ40, p-tau181, and p-tau217 showed significant associations with Aβ-PET status, (adjusted odds ratio [AOR] of 1.

Plasma biomarkers, brain amyloid pathology, and cortical thickness in a diverse middle-aged community cohort: the HCP-CoBRA study.

Introduction: We evaluated plasma biomarker association with, and classification accuracies for, Aβ-PET and cortical thickness in the biracial HCP-CoBRA cohort (53% B/AA and 47% NHW).

Methods: In n=218 participants (age 62 [range: 57-71] years, 65% female and 15% Aβ PET-positive), plasma biomarkers (p-tau181, p-tau217, p-tau231, GFAP, NfL, Aβ42/Aβ40) were compared to Aβ-PET and MRI neuroimaging indicators.

Results: P-tau217 (Janssen and ALZpath [AUCs=0.

Pittsburgh plasma p-tau217: Classification accuracies for autosomal dominant and sporadic Alzheimer's disease in the community.

Introduction: Most available phosphorylated tau (p-tau)217 immunoassays have similar performance. It is unclear if this is due to the use of the same antibody (the "ALZpath antibody"). We established and evaluated a novel p-tau217 assay that uses an alternative antibody and benchmarked the results against ALZpath-p-tau217.

Impact of racialization on neuroimaging and plasma biomarkers of Alzheimer's disease.

Introduction: Given the predominance of imaging and plasma biomarkers in Alzheimer's disease observational studies and clinical trials, it is critical to understand the differences between these biomarkers across racialized groups.

Methods: A total of 260 older adults without dementia racialized as Black and/or African American (AA) and non-Hispanic white (NHW), ranging in age from 50 to 90 years (68.8 ± 9.

Equivalence of Plasma and Serum for Clinical Measurement of p-tau217: Comparative Analyses of Four Blood-Based Assays.

Phosphorylated tau (p-tau) 217 is a promising blood biomarker for Alzheimer's disease (AD). However, most p-tau217 assays have been validated solely in ethylenediaminetetraacetic acid (EDTA) plasma, leaving the clinical applicability of serum p-tau217 largely unexplored despite serum being a preferred matrix in many clinical laboratories. To address this gap, we compared p-tau217 concentrations and classification accuracies in matched plasma and serum samples in four research-use-only assays.

PET-measured amyloid beta accumulates at an accelerated rate in Down syndrome compared to neurotypical populations.

Introduction: Individuals with Down syndrome (DS) have a high prevalence of Alzheimer's disease (AD) and reveal an earlier age of amyloid beta (Aβ) onset compared to sporadic AD. Differences in amyloid accumulation rates between DS and sporadic AD populations have not been established.

Methods: Participants with ≥ 3 [C-11]PiB scans (spanning > 6 years) and transitioning to Aβ+ were included, resulting in 20 DS and 23 neurotypical (NT) participants.

A brief history of Aβ imaging.

β-Amyloid (Αβ) imaging revolutionized the in vivo assessment of Alzheimer's disease (AD) Αβ pathology and its changes over time, increasing our insights into Aβ deposition in the brain by providing highly accurate, reliable, and reproducible quantitative statements of regional and global Aβ burden in the brain, proving essential for the differential diagnosis, staging, and evaluation of disease-specific anti-Αβ therapeutic approaches. Longitudinal observations, coupled with different disease-specific biomarkers to assess potential downstream effects of Aβ, have confirmed that Αβ deposition in the brain starts decades before the onset of symptoms. Aβ imaging studies continue to refine our understanding of the role of Αβ deposition in AD, and its relation to other imaging and fluid biomarkers.

Pittsburgh plasma p-tau217: classification accuracies for autosomal dominant and sporadic Alzheimer's disease in the community.

Introduction: Most available p-tau217 immunoassays have similar performances. It is unclear if this is due to the use of the same antibody (the "ALZpath antibody"). We established and evaluated a novel p-tau217 assay that employs an alternative antibody, and benchmarked the results against ALZpath-p-tau217.

Plasma biomarkers identify brain ATN abnormalities in a dementia-free population-based cohort.

Introduction: Using the ATN framework, we evaluated the potential of plasma biomarkers to identify abnormal brain amyloid-beta (Aβ) positron emission tomography (PET), tau-PET and neurodegeneration in a socioeconomically disadvantaged population-based cohort.

Methods: Community-dwelling dementia-free (n=113, including 102 (91%) cognitively normal) participants underwent ATN neuroimaging and plasma biomarker assessments.

Results: Plasma Aβ42/Aβ40, p-tau181, and p-tau217 showed significant associations with Aβ-PET status (adjusted odds ratio [AOR] of 1.

Emotional distress following amyloid PET result disclosure: Heightened among those with cognitive symptoms.

Introduction: We examined differences in emotional distress following amyloid positron emission tomography (PET) results disclosure across the cognitive spectrum, including individuals who are cognitively unimpaired, with mild cognitive impairment (MCI), and dementia.

Methods: Seventy-five participants from the University of Pittsburgh Alzheimer's Disease Research Center who completed baseline PET and an initial follow-up call were included in the analysis. Multiple linear regression was employed to examine differences in distress among diagnostic groups, as measured by Impact of Genetic Testing for Alzheimer's Disease (IGT-AD) adapted for amyloid PET.

Brain Morphometrics Correlations With Age Among 350 Participants Imaged With Both 3T and 7T MRI: 7T Improves Statistical Power and Reduces Required Sample Size.

Magnetic resonance imaging (MRI) at 7T has a superior signal-to-noise ratio to 3T but also presents higher signal inhomogeneities and geometric distortions. A key knowledge gap is to robustly investigate the sensitivity and accuracy of 3T and 7T MRI in assessing brain morphometrics. This study aims to (a) aggregate a large number of paired 3T and 7T scans to evaluate their differences in quantitative brain morphological assessment using a widely available brain segmentation tool, FreeSurfer, as well as to (b) examine the impact of normalization methods for subject variability and smaller sample sizes on data analysis.

Impact of the polygenic risk scores for attention-deficit/hyperactivity disorder in Alzheimer's disease.

Introduction: Epidemiological studies indicate a link between attention-deficit/hyperactivity disorder (ADHD) and elevated risk of dementia. However, the impact of ADHD on cognition and Alzheimer's disease (AD) biomarkers in individuals with cognitive impairment remains unclear.

Methods: We computed weighted ADHD polygenic risk scores (ADHD-PRS) in 938 cognitively impaired participants (674 mild cognitive impairment [MCI] and 264 dementia; mean age 73.

Novel plasma biomarkers of amyloid plaque pathology and cortical thickness: Evaluation of the NULISA targeted proteomic platform in an ethnically diverse cohort.

Introduction: Proteomic evaluation of plasma samples could accelerate the identification of novel Alzheimer's disease (AD) biomarkers. We evaluated the novel NUcleic acid Linked Immuno-Sandwich Assay (NULISA) proteomic method in an ethnically diverse cohort.

Methods: Plasma biomarkers were measured with NULISA in the Human Connectome Project, a predominantly preclinical biracial community cohort in southwestern Pennsylvania.

Whole-genome sequencing reveals the impact of lipid pathway and APOE genotype on brain amyloidosis.

Amyloid-PET imaging tracks the accumulation of amyloid beta (Aβ) deposits in the brain. Amyloid plaques accumulation may begin 10 to 20 years before the individual experiences clinical symptoms associated with Alzheimer's diseases (ad). Recent large-scale genome-wide association studies reported common risk factors associated with brain amyloidosis, suggesting that this endophenotype is driven by genetic variants.

Rethinking the residual approach: leveraging statistical learning to operationalize cognitive resilience in Alzheimer's disease.

Cognitive resilience (CR) describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer's disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be directly observed. The residual approach has been widely applied to estimate CR, where the degree of resilience is estimated through a linear model's residuals.

Equivalence of plasma and serum for clinical measurement of p-tau217: comparative analyses of four blood-based assays.

Background: Phosphorylated tau (p-tau) 217 is a promising blood biomarker for Alzheimer's disease (AD). However, most p-tau217 assays have been validated solely in ethylenediaminetetraacetic acid (EDTA) plasma, leaving the clinical applicability of serum p-tau217 largely unexplored despite serum being a preferred matrix in many clinical laboratories. To address this gap, we compared p-tau217 concentrations and diagnostic performances in matched plasma and serum samples using four research-use-only assays, including three from commercial sources i.

Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer's disease.

Background: Blood-based biomarkers are gaining grounds for the detection of Alzheimer's disease (AD) and related disorders (ADRDs). However, two key obstacles remain: the lack of methods for multi-analyte assessments and the need for biomarkers for related pathophysiological processes like neuroinflammation, vascular, and synaptic dysfunction. A novel proteomic method for pre-selected analytes, based on proximity extension technology, was recently introduced.

Implementation and Assessment of Tau Thresholds in Non-Demented Individuals as Predictors of Cognitive Decline in Tau Imaging Studies.

Background: Tau accumulation in Alzheimer's disease is associated with short term clinical progression and faster rates of cognitive decline in individuals with high amyloid-β deposition. Defining an optimal threshold of tau accumulation predictive of cognitive decline remains a challenge.

Objective: We tested the ability of regional tau PET sensitivity and specificity thresholds to predict longitudinal cognitive decline.

Associations of endogenous estrogens, plasma Alzheimer's disease biomarkers, and carrier status on regional brain volumes in postmenopausal women.

Background: Women carrying the allele are at greater risk of developing Alzheimer's disease (AD) from ages 65-75 years compared to men. To better understand the elevated risk conferred by carrier status among midlife women, we investigated the separate and interactive associations of endogenous estrogens, plasma AD biomarkers, and carrier status on regional brain volumes in a sample of late midlife postmenopausal women.

Methods: Participants were enrolled in MsBrain, a cohort study of postmenopausal women ( = 171, mean age = 59.