Biomarkers.

Background: The variability in the regional distribution of Aβ-PET signal and its relation to clinical features is debated. We used data-driven approaches to uncover heterogeneity in cortical Aβ-PET signal from a large representative sample collected through the IDEAS study.

Methods: We analysed cross-sectional Aβ-PET collected from 10,361 patients with MCI or mild dementia scanned in 295 PET facilities using one of the 3 FDA-approved tracers.

Biomarkers.

Background: Osteoarthritis (OA) is a degenerative disorder of bone aging and risk factor for cognitive decline. Bone morphogenetic proteins (BMPs) are growth factor proteins that regulate skeletal and neural development, and circulating BMPs may mediate molecular cross-talk between bone and brain. The present study examined plasma BMP levels in relation to OA and neurobehavioral outcomes in cognitively unimpaired (CU) older adults.

Biomarkers.

Background: The high prevalence of mixed-pathology dementias suggests that multi-drug treatments may improve clinical outcomes; thus, in-vivo biomarkers for co-pathologies are needed. We investigated a novel assay for detecting seeds of misfolded alpha synuclein (αSyn) and explored its relationship to outcomes including Alzheimer's disease (AD) biomarkers, clinical features, and cognitive trajectories, in two community-based cohorts enriched for AD risk.

Method: Cerebrospinal fluid (CSF) obtained from participants in the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center (N=418 participants; 515 LPs; Table 1) was assayed using a clinically validated, qualitative Syn seed amplification assay (SAA; Amprion).

Biomarkers.

Background: Alzheimer's disease (AD), Dementia with Lewy Bodies (DLB), and other neurodegenerative diseases (NDD) develop over an extended preclinical period, sharing common risk factors and underlying pathophysiological mechanisms. Plasma proteins, including Amyloid-beta peptides (Aβ) and Tau isoforms, facilitate differential diagnosis of NDD in their earliest stages, allowing for timely delivery of targeted interventions. Blood-based biomarkers may also serve as a reliable means of monitoring disease progression and evaluating the effectiveness of individualized interventions across the spectrum of disease.

Biomarkers.

Background: Cognitive Reserve (CR) refers to the brain's ability to maintain optimal cognitive function despite damage or pathology. The neural implementation of CR is a major research focus, and resting-state functional connectivity (RSFC) has emerged as a promising imaging correlate of CR. We assessed RSFC as a function of two different proxy measures of CR and further assessed the impact of these brain networks on longitudinal cognitive performance in a sample of cognitively unimpaired (CU) individuals at risk of Alzheimer's disease (AD).

Biomarkers.

Background: The HEAD study aims to collect a large dataset of multiple tau-PET tracers to provide robust anchor values for tau-PET harmonization. Here, we tested the hypothesis that anchoring two tau tracer uptake values using head-to-head measurements has the potential to generate an accurate universal tau-PET scale, named Uniτ(tau).

Methods: We assessed 200 individuals across the aging and AD spectrum (Training: HEAD data freeze 2.

Biomarkers.

Background: Physical activity (PA) is associated with lower dementia risk; however, underlying molecular pathways are poorly understood. We leveraged large-scale plasma proteomics to identify biological signatures of objectively-monitored PA in cognitively unimpaired (CU) older adults and cross-validated signatures in independent exercise intervention and Alzheimer's disease (AD) cohorts.

Method: Discovery cohort included 65 CU adults (mean = 76.

Biomarkers.

Background: With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. We evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles.

Method: Plasma %p-tau217 (ratio of phosporylated-tau217 to non-phosphorylated mid-region tau) was analyzed by mass spectrometry in the Swedish BioFINDER-2 cohort (n=1,422) and the US Knight ADRC cohort (n=337, Table 1).

Biomarkers.

Background: Early-onset Alzheimer's disease (EOAD), manifesting before age 65, demands nuanced diagnostic approaches. FDG18-PET unveils metabolic insights, the MRI scale captures structural changes, and ACE-R assesses cognitive impairment details. A holistic evaluation enhances diagnostic precision and enriches our understanding of cognitive decline in early-onset presentations.

Biomarkers.

Background: APOE-ɛ4 is a major risk factor for Alzheimer's disease (AD); its effects have been examined in late-onset AD (LOAD) but less so in early-onset AD (EOAD). In LOAD, APOE genotype has strong effects on episodic memory and medial temporal lobe (MTL) atrophy (Wolk & Dickerson, 2010). However, EOAD often presents with more cognitive impairments in executive function, language, and visuospatial abilities than memory.

Biomarkers.

Background: Individuals with Mild Cognitive Impairment (MCI) are at greater risk of developing Alzheimer's disease (AD). Previous studies have shown that physical exercise is a protective factor against the clinical evolution of dementia in MCI. Lower muscle strength levels are associated with a greater risk of AD incidence.

Biomarkers.

Background: Identification of useful fluid biomarkers is expected to advance frontotemporal dementia spectrum disorders (FTD) care and therapeutic development. The clinical utility of emerging plasma Amyloid, Tau, and Neurodegeneration (ATN) biomarkers in FTD remains unexplored. This study analyzed ATN patterns by sporadic FTD phenotype, based on amyloid beta (Aβ), amyloid beta (Aβ), phospho-tau217 (p-tau217), and neurofilament (NfL) plasma concentrations.

Biomarkers.

Background: Blood-based biomarkers offer a cost-effective and simple alternative for clinical use in the context of Alzheimer's disease (AD). It has already been shown that plasma phosphorylated tau at threonine 217 (p-tau217) is associated with amyloid (Aβ), neurofibrillary tau tangles, and cognitive decline. Longitudinal studies confirmed its ability to track AD progression.

Biomarkers.

Background: Neuropathological studies indicate that locus coeruleus(LC) volume decreases in Alzheimer's disease(AD) by 8% at each stage, (from Braak 0-1), whereas in normal aging, the LC remains unchanged. These changes make LC volumetry by neuroimaging a promising way to track AD progression even before symptoms appear. However, LC's small size and location make it prone to imaging artifacts.

Biomarkers.

Background: There is a significant need for biomarkers of neurodegenerative burden in Early-onset Alzheimer's disease (EOAD). Evidence suggests that levels of specific CSF biomarkers (e.g.

Biomarkers.

Background: Prior work has advanced our understanding of cortical atrophy in early-onset Alzheimer's disease (EOAD), but longitudinal data are sparse. Current longitudinal MRI studies point to progressive atrophy in cerebral cortex exhibiting a posterior-to-anterior gradient, but these studies include small samples with mostly amnestic EOAD. Here, we analyzed a large sample of sporadic EOAD patients from the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) to test the central hypothesis that areas in our recently described EOAD signature (Touroutoglou et al.

Biomarkers.

Background: Identifying individuals' levels of tau PET pathology could prove to be beneficial in clinical settings, given that emerging therapies aimed reducing Aβ seem to be most effective in these individuals. Here, we present the cases of four patients who visited the memory clinic at the University of Pittsburgh Medical Center between June and December 2023 and underwent both Aβ and tau-PET scans.

Method: These individuals had standard clinical and cognitive outcomes, typical blood tests order in patients with memory impairment, MRI, and, as part of the HEAD study, PET PIB Aβ and two tau PET tracers (MK6240 and Flortaucipir).

Biomarkers.

Background: Tau PET tracers are employed to measure the accumulation of tau in vivo in the brain. Each tau tracer possesses unique characteristics, including binding affinity, sensitivity, and specificity to tau aggregates. This study leverages the HEAD study dataset, which is currently performing baseline tau PET tracers and conducting multiple clinical and cognitive assessments.

Biomarkers.

Background: Medial temporal lobe (MTL) atrophy is an early feature of multiple neurodegenerative diseases. In genetic frontotemporal lobar degeneration (FTLD, i.e.

Biomarkers.

Background: Utilizing PET amyloid-beta (Aβ) and tau for staging Alzheimer's Disease (AD) has demonstrated potential in identifying individuals with varying degrees of disease severity, applicable to both clinical trials and practice. However, the diverse binding characteristics of tau tracers pose challenges to the application of this staging across different ligands. In this study, we evaluate a novel staging framework proposed by the AA working group, employing Aβ PET and either [F]MK6240 or [F]Flortaucipir in individuals participating in a head-to-head study of tau PET tracers.

Biomarkers.

Several new blood-based biomarkers (BBMs) of Alzheimer's disease and related neuropathologies have completed late-stage validation and are beginning to be used in the clinical setting. However, the role of BBMs in various clinical settings, especially their specific context-of-use, remains an open question for the field. Several studies are beginning to systematically collect information on BBM real-word diagnostic performance, but as BBMs transition from research settings to clinical implementation, experience from clinical providers in specialty centers can inform and guide use.

Biomarkers.

Background: The timing of tau-PET accumulation and cognitive decline in sporadic early-onset Alzheimer's disease (eoAD, age-at-onset<65) has not been established and is needed to optimize tau-PET as an outcome measure in clinical trials. Here we leverage large-sample, longitudinal data from the Longitudinal Early-onset Alzheimer's Disease Study (LEADS) to model tau-PET accumulation in three regions relative to cognitive decline.

Method: Longitudinal [F]Flortaucipir-PET (FTP) and CDR-SB scores were acquired in 195 amyloid-PET-positive, sporadic eoAD patients with MCI or mild dementia due to AD at baseline (Table 1).

Biomarkers.

Background: Dementia, encompassing Alzheimer's disease (AD) and frontotemporal dementia (FTD), poses a substantial public health challenge in Latin America. Barriers such as a shortage of healthcare professionals, limited medical accessibility, and underdiagnosis contribute to the complexity. While biomarkers aligned with the ATN framework (Amyloid, Tau, Neurodegeneration) have revolutionized diagnosis, their cost limits adoption in Latin America.

Biomarkers.

Background: Normative models (NM) of brain metrics based on large, diverse populations offer novel strategies to detect individual brain abnormalities. To create an age-dependent statistical model of brain microstructure over the human lifespan, we built the largest multi-site NM of white matter (WM) diffusion tensor imaging (DTI) metrics based on 54,591 subjects. We used state-of-the-art tools to adjust for site-dependent effects.

Biomarkers.

Background: The Centiloid framework was developed to harmonize amyloid-PET quantification across radiotracers and processing pipelines to facilitate data sharing and merging; it is now widely used across research and clinical trials. As we just completed the quantification of 10,361 amyloid-PET scans from the largest "real-world" study of amyloid-PET (IDEAS) and are about to release the data, we aimed to compare the distribution of IDEAS Centiloid values with other available datasets.

Method: In IDEAS, amyloid scans were acquired across 343 facilities and centrally processed at UCSF using a PET-only pipeline.