Biomarkers.

Background: There is emerging evidence to substantiate temporal proximity to parental onset (PPO) of dementia as a proxy stage marker in studies of late onset Alzheimer's Disease (AD). PPO predicts accrual of amyloid pathology cross-sectionally and longitudinally. However interactions with gender, age, and APOE-𝜀4 carriage have been inconsistent across datasets and amyloid measures.

Biomarkers.

Background: Lewy body pathology consisting of aggregated alpha-Synuclein (a-Syn) is the hallmark pathology in Parkinson's disease, yet a-Syn aggregates are also commonly observed post-mortem as a co-pathology in Alzheimer's disease (AD) patients. Preclinical research has shown that a-Syn can amplify Ab-associated tau seeding and aggregation, hence a-Syn co-pathology may contribute to the Ab-induced progression of tau pathology in AD. To address this, we combined a novel CSF-based RT-QuIC seed-amplification assay to determine a-Syn positivity, with PET-neuroimaging in a large patient cohort ranging from cognitively normal to dementia, to determine whether a-Syn co-pathology accelerates Ab-driven tau accumulation.

Biomarkers.

Background: Hippocampal volume is an acknowledged biomarker of neurodegenerative disease, including Alzheimer's disease (AD). However, the relationship between other subcortical brain structures and dementia risk is uncertain and may differ by disease stage. We aimed to assess the prognostic value of subcortical volumes for dementia risk across different disease stages by investigating memory clinic-based populations and community-dwelling individuals.

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: Synaptic loss is a key feature of Alzheimer's disease (AD) dementia. In the entorhinal cortex (ERC) and hippocampus, phosphorylated tau (pTau) colocalizes with synaptosomes, and its presence may play a role in AD-related synaptic loss. However, the relationship between pTau and synaptic density is not well understood.

Biomarkers.

Background: Alzheimer's disease (AD) is identified by the accumulation of amyloid β (Aβ) and tau proteins in the brain. The NeuroToolKit offers automated cerebrospinal fluid (CSF) immunoassays of core AD biomarkers and biomarkers of neurodegeneration and synaptic function, including neurofilament light (NfL), SNAP-25, and neuronal pentraxin 2 (NPTX2). This work explores whether these three markers predict pre-dementia cognitive decline synergistically with or after accounting for CSF ptau/Aβ.

Biomarkers.

Background: In murine models, peripheral blood factors have been identified as having either a brain rejuvenating or ageing effect. However, it is unclear whether these blood factors have similar effects in humans. We aimed at testing the association between these blood factors and cognitive performance in cognitively unimpaired (CU) individuals at risk of Alzheimer's disease (AD).

Biomarkers.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease with multifactorial etiology. The toxicity of senile plaques and neurofibrillary tangles is associated with changes in the clearance of tau and beta-amyloid proteins, which are closely related to inflammatory imbalances. Pro-inflammatory cytokines are present in abnormal details due to the overactivation of immunological pathways, especially toll-like receptors.

Systematic review of integrated mental and physical health services for children and young people with eating and functional symptoms.

Background: Evidence suggests that by recognising the psychosocial component of illness as equally important to the biological components, care becomes more holistic, and patients can benefit. Providing this type of care requires collaboration among health professionals, rather than working in isolation, to achieve better outcomes. However, there is a lack of evidence about the implementation of integrated health care.

Biomarkers.

Background: Blood-based biomarkers (BBM) are emerging as minimally invasive, scalable and relatively low-cost options for discriminating different neurodegenerative diseases. Before implementation in clinical practice can take place, it is important to determine their real-world clinical validity in patients presenting at a memory clinic. Therefore, we prospectively evaluated changes in diagnosis and diagnostic confidence resulting from the use of a BBM panel tailored to common differential diagnostic considerations (Verberk et al.

Biomarkers.

Background: Precision neuroscience is emerging as a transformative approach that aims to identify the right treatment for the right patient at the right time. To enable this, it is important to move beyond the categorization of patients based on clinical symptoms towards a biological definition of disease. For Alzheimer's disease, significant progress has been made in this direction, with the development of the "A/T/N" biomarker framework that classifies patients based on underlying pathophysiology.

Biomarkers.

Background: The common marmoset (Callithrix jacchus) is an important animal model in neuroscience and neurological diseases, presenting primate-specific evolutionary features such as an expanded frontal cortex. We established a new consortium with funding support from the National Institute on Aging to generate, characterize, and validate MArmosets as Research MOdels of AD (MARMO-AD). This consortium develops and studies gene-edited marmoset models carrying genetic risk for AD, comparing them against wild-type aging marmosets from birth throughout their lifespan, using non-invasive longitudinal 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: The common marmoset (Callithrix jacchus) is an important animal model in neuroscience and neurological diseases (e.g., Alzheimer's disease - AD), as they present primate-specific evolutionary features such as an expanded frontal cortex.

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: Rise in plasma phospho-tau (pTau) is hypothesized to reflect a physiological response to brain Aβ plaques, preceding the formation of neurofibrillary tangles (NFT). An alternate explanation is poor sensitivity of tau PET for detection of early NFT formation. The tau tracer MK6240 has very low background "off-target" binding and may better detect early tau aggregation.

Biomarkers.

Background: Plasma phospho-tau biomarkers, such as p217+tau, excel at identifying Alzheimer's Disease (AD) neuropathology. However, questions remain regarding their capacity to inform AD biological PET stages at group level and maintain the same precision at individual patient level.

Method: Participants included 248 cognitively unimpaired (CU) and 227 cognitively impaired (CI) individuals, with Janssen plasma p217+tau Simoa® assay, F-NAV4694 Aβ PET (A) and F-MK6240 tau PET (T) data.

Biomarkers.

Background: Blood-based biomarkers are increasingly able to identify Alzheimer's Disease pathology in the preclinical stages of the disease. These biomarkers hold promise to study development and progression of the disease. Our aim is to investigate the longitudinal trajectories of Aβ ratio, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) in individuals with subjective cognitive decline (SCD).

Biomarkers.

Background: The common marmoset (Callithrix jacchus) is an important animal model in neuroscience and neurological diseases (e.g., Alzheimer's disease - AD), as they present primate-specific evolutionary features such as an expanded frontal cortex.

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: Blood-based Alzheimer's disease (AD) biomarkers have been increasingly employed for diagnostic and prognostic purposes, thanks to high diagnostic accuracy in distinguishing AD from healthy controls or other dementia types. p-tau217 exhibits stronger associations with AD hallmarks in CSF and brain, compared to other p-tau isoforms. Furthermore, the majority of these studies have been conducted in non-Hispanic Whites, limiting our understanding of the performances and utility of these biomarkers across ethnicities.

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.

Biomarkers.

Background: To date, limited data exist concerning the utility of FDG-PET in detecting Alzheimer's Disease (AD) in Down Syndrome (DS). Yet, sensitive biomarkers for neurodegeneration are essential in this population genetically predisposed for AD. Therefore, we aimed at characterizing the effect of age, disease stage and AD pathology on brain metabolism in a large cohort of adults with DS.