Amyloid is associated with accelerated atrophy in cognitively unimpaired individuals.

Introduction: This study examined the association of longitudinal atrophy with baseline cerebrospinal fluid (CSF) amyloid beta (Aβ, A) and phosphorylated tau (p-tau, T) biomarkers (Aβ42/40, p-tau181) in 406 cognitively unimpaired (CU) individuals (6.670 years of follow-up on average, up to 13 imaging visits) to assess whether A+ is associated with Alzheimer's disease-like atrophy and whether this depends on p-tau181 levels.

Methods: An A-T- CU group free from abnormal neurodegeneration (N) was identified using a robust normative approach and used to model normal age-related atrophy via -scoring.

Comparison of sample characteristics of Wisconsin Alzheimer's Disease Research Center participants with the Wisconsin state population-An evaluation of the recruitment effort.

Introduction: Understanding how a research sample compares to the population from which it is drawn can help inform future recruitment planning. We compared the Wisconsin Alzheimer's Disease Research Center (WADRC) participant sample to the Wisconsin state population (WI-pop) on key demographic, social exposome, and vascular risk measures.

Methods: The WADRC sample included 930 participants.

Delayed primacy recall in AVLT is associated with medial temporal tau PET burden in cognitively unimpaired adults.

Background: Alzheimer's disease (AD) can be diagnosed by in vivo abnormalities of amyloid-β plaques (A) and tau accumulation (T) biomarkers. Previous studies have shown that analyses of serial position performance in episodic memory tests, and especially, delayed primacy, are associated with AD pathology even in individuals who are cognitively unimpaired. The earliest signs of cortical tau pathology are observed in medial temporal lobe (MTL) regions, yet it is unknown if serial position markers are also associated with early tau load in these regions.

Targeted Proteomic Biomarker Profiling Using NULISA in a cohort enriched with risk for Alzheimer's Disease and Related Dementias.

Introduction: Targeted proteomic assays may be useful for diagnosing and staging Alzheimer's disease and related dementias (ADRD). We evaluated the performance of a 120-marker central nervous system (CNS) NUcleic acid-Linked Immuno-Sandwich Assay (NULISA) panel in samples spanning the AD spectrum.

Methods: Cross-sectional plasma samples (n=252) were analyzed using Alamar's NULISAseq CNS panel.

Visual read of [F-18]florquinitau PET that includes and extends beyond the mesial temporal lobe is associated with increased plasma pTau217 and cognitive decline in a cohort that is enriched with risk for Alzheimer's disease.

Introduction: Patterns of signal from tau positron emission tomography (tau-PET) confined to the medial temporal lobe (MTL) or extended into the neocortex may be relevant for Alzheimer's disease (AD) research if they are linked to differential biomarker levels and cognitive decline.

Methods: Visual assessment of Tau-PET [F-18]florquinitau (FQT) exams from 728 initially non-demented older adults yielded four uptake groups: tau-negative (T-), MTL-only (T+), neocortex-only (T+), or both (T+). Mixed effects models assessed group differences in retrospective cognitive and plasma pTau217 trajectories.

Misfolded alpha synuclein co-occurrence with Alzheimer's disease proteinopathy.

Introduction: Multi-etiology dementia necessitates in-vivo markers of copathologies including misfolded -synuclein (syn). We measured misfolded syn aggregates (syn-seeds) via qualitative seed amplifcation assays (synSAA) and examined relationships with markers of Alzheimer's disease (AD).

Methods: Cerebrospinal fluid (CSF) was obtained from 420 participants in two Wisconsin AD risk cohorts (35% male; 91% cognitively unimpaired; mean (SD) age, 65.

Story recall performance and AT classification via positron emission tomography: A comparison of logical memory and Craft Story 21.

Background: Early detection of Alzheimer's disease (AD) is one of the critical components of the global response to the growing dementia crisis. Analysis of serial position performance in story recall tests has yielded sensitive metrics for the prediction of AD at low cost. In this study, we examined whether serial position markers in two story recall tests (the logical memory test, LMT, and the Craft Story 21 test, CST) were sensitive to cross-sectional biomarker-based assessment of in vivo neuropathology.

Longitudinal plasma phosphorylated-tau217 and other related biomarkers in a non-demented Alzheimer's risk-enhanced sample.

Introduction: Understanding longitudinal change in key plasma biomarkers will aid in detecting presymptomatic Alzheimer's disease (AD).

Methods: Serial plasma samples from 424 Wisconsin Registry for Alzheimer's Prevention participants were analyzed for phosphorylated-tau217 (p-tau217; ALZpath) and other AD biomarkers, to study longitudinal trajectories in relation to disease, health factors, and cognitive decline. Of the participants, 18.

Communicating Alzheimer's biomarker results to cognitively unimpaired research participants: Satisfaction, utility, and impact on research attitudes.

Introduction: Recruitment and retention pose a significant challenge to Alzheimer's disease (AD) research. Returning AD biomarker results to participants has been proposed as a means to improve recruitment and retention. We present findings related to participant satisfaction, utility, and impact on research attitudes from the amyloid positron emission tomography (PET) disclosure sub-study within the Wisconsin Registry for Alzheimer's Prevention (WRAP).

CSF Biomarkers in Longitudinal Alzheimer Disease Cohorts: Pre-Analytic Challenges.

Background: The sensitivity of amyloid to pre-analytic factors complicates cerebrospinal fluid (CSF) diagnostics for Alzheimer disease. We report reliability and validity evidence for automated immunoassays from frozen and fresh CSF samples in an ongoing, single-site research program.

Methods: CSF samples were obtained from 2 Wisconsin cohorts (1256 measurements; 727 participants).

Associations between recall of proper names in story recall and CSF amyloid and tau in adults without cognitive impairment.

Neuropsychological measures sensitive to decline in the preclinical phase of Alzheimer's disease are needed. We previously demonstrated that higher amyloid-beta (Aβ) assessed by positron emission tomography in adults without cognitive impairment was associated with recall of fewer proper names in Logical Memory story recall. The current study investigated the association between proper names and cerebrospinal fluid biomarkers (Aβ, phosphorylated tau [pTau], neurofilament light) in 223 participants from the Wisconsin Registry for Alzheimer's Prevention.

Neuroimaging of tissue microstructure as a marker of neurodegeneration in the AT(N) framework: defining abnormal neurodegeneration and improving prediction of clinical status.

Background: Alzheimer's disease involves accumulating amyloid (A) and tau (T) pathology, and progressive neurodegeneration (N), leading to the development of the AD clinical syndrome. While several markers of N have been proposed, efforts to define normal vs. abnormal neurodegeneration based on neuroimaging have been limited.

Anticipated Psychological or Behavioral Reactions to Learning Alzheimer Biomarker Results: Associations With Contextual Factors.

Background: As Alzheimer disease (AD) biomarker testing becomes more widely available, adults may opt to learn results. Considering potential reactions to learning biomarker results can guide prebiomarker and postbiomarker testing education and counseling programs.

Methods: Cognitively healthy adults enrolled in observational Alzheimer research responded to a telephone survey about learning AD risk information (n=334; 44% Black or African American; mean age=64.

Informing Disclosure: Efficacy of a Brief Educational Intervention on Research Participants' Knowledge about Alzheimer's Disease Biomarkers.

Recommendations for communicating Alzheimer's disease (AD) biomarkers include pre-disclosure participant education and counseling, to allow individuals to make an informed decision. In a cohort of largely non-Hispanic White, cognitively unimpaired older adults from the Wisconsin Registry for Alzheimer's Prevention, we conducted a structured amyloid PET disclosure process that included knowledge assessment and education. Baseline participant knowledge about AD biomarkers and research was high, but information needs existed around dementia causes, early AD symptoms, genetic information, and psychosocial consequences of disclosure.