Biomarkers.

Background: Stronger default mode (DMN) and bilateral frontoparietal control network (FPCN) resting-state functional connectivity are associated with reduced β-amyloid (Aβ)-related cognitive decline in cognitively unimpaired older adults, who were predominantly Aβ negative. This suggests that these networks might support cognitive resilience in the face of early AD pathology but it remains unclear whether these effects are apparent in preclinical AD. We investigated whether left-FPCN, right-FPCN, and DMN connectivity moderated the effect of Aβ on cognitive decline using a large multi-site dataset from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study.

Biomarkers.

Background: Individuals from diverse racial and ethnic groups are severely underrepresented in AD trials in part due to disproportionate biomarker ineligibility. Evidence from recent studies support plasma phosphorylated tau (P-tau217) as an early marker for brain Aβ pathology and a reliable marker in predicting elevated brain amyloid PET in cognitively unimpaired adults. We examined the relationship between P-tau217 and florbetapir PET standard uptake value ratios (SUVR) by self-reported racial and ethnic groups in preclinical AD studies.

Biomarkers.

Background: Data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial (NCT02008357), including cognitively unimpaired participants with brain amyloid pathology on florbetapir F 18, demonstrates that levels of plasma P-tau217, as detected by an electrochemiluminescence (ECL) immunoassay, is strong predictor of elevated cerebral amyloid on florbetapir PET in cognitively unimpaired individuals. Here we compare plasma P-tau217 measures over 12 weeks using a P-tau217 ECL immunoassay.

Method: A4 trial placebo-group participants who had their first baseline and first post-baseline plasma P-tau217 samples collected within 175 days of each other were included in these analyses.

Biomarkers.

Background: Estimating the time course of locus coeruleus integrity changes is important for a better understanding of the pathophysiological cascade and for identifying the optimal window of opportunity for prevention trials. We used samples iterative local approximation (SILA) to determine the individual estimated time of onset of low LC integrity and related this to early cortical tau deposition and cognitive decline.

Methods: 101 individuals from the Harvard Aging Brain Study+ with longitudinal 3T MRI-LC imaging, 18F-Flortaucipir (FTP)-PET imaging (n=92 with longitudinal data), longitudinal cognitive assessments and baseline PiB-PET imaging were included (mean age: 69.

Biomarkers.

Background: Tau-PET imaging allows in-vivo detection of neurofibrillary tangles. One tau-PET tracer (i.e.