Biomarkers.

Background: Blood-based biomarkers (BBM) for Alzheimer's disease (AD) may be able to identify individuals eligible for emerging anti-amyloid treatments (DMT). We aimed to evaluate how to use BBM as (pre-) selection tools for DMTs by simulating different triaging scenarios in a memory clinic setting.

Methods: We included 1199 participants from the Amsterdam Dementia Cohort with measured BBM (plasma pTau181, GFAP and NfL) and used a predefined Youden-index based cut point for amyloid positivity (method: https://doi.

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: 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 Alzheimer's disease (AD) research framework proposes a biological definition of the disease. Still, little is known about longitudinal dynamics of core AD biomarker trajectories and how they map to each stage on the clinical spectrum.

Methods: Participants with abnormal amyloid across the cognitive spectrum (i.

Biomarkers.

Background: Plasma levels of amyloid-β, and glial fibrillary acidic protein (GFAP) have demonstrated predictive potential for amyloid pathology in the early stages of Alzheimer's disease (AD) development. Utilizing baseline and up to 6-year follow-up plasma, positron emission tomography (PET) and cognitive data from cognitively unimpaired individuals, we here aim to test whether early changes in plasma biomarker levels associate with change in amyloid status and cognitive decline.

Methods: From the EMIF-AD PreclinAD study we selected individuals with normal cognition and longitudinal plasma, PET and cognitive data available (n=200, table 1).

Biomarkers.

Background: Atherosclerosis, the hardening of arterial walls resulting in atherosclerotic plaques, is linked to cognitive dysfunction and an increased risk of cognitive decline. Findings on the impact of high coronary artery calcium (CAC), a subclinical atherosclerosis biomarker, on cognition remain inconsistent. Additionally, its effect on Alzheimer's Disease (AD) biomarkers has not been previously analysed.

Biomarkers.

Background: Down syndrome (DS, trisomy 21) is the most frequent genetic cause of intellectual disability (ID), prevalent in approximately 1 in 900 live births (Loane et al., 2013). People with DS are at high risk to develop Alzheimer's disease dementia (AD) (Lott & Head, 2001).

Developing Topics.

Background: Among the different phospho-tau sites, phosphorylation at Threonine 205 (pTau205) in CSF has been shown to be closely associated with Tau-PET (Lantero-Rodriguez et al. 2024; Barthélemy et al. 2023).

Developing Topics.

Background: Plasma tau phosphorylated at Threonine181 (pTau181) has been extensively studied as an accessible biomarker of amyloid pathology and is compared in various studies with other pTau epitopes. ADx has developed a Quanterix Homebrew Simoa assay using a highly pTau181 specific capture mAb (ADx252) and an N-terminal tau detector ADx204 demonstrating high clinical performance (Janelidze et al., 2023; Ashton et al.

Developing Topics.

Background: p-Tau 217 is considered the most accurate single plasma biomarker for detecting amyloid pathology. Recent draft Alzheimer's Association criteria for diagnosing Alzheimer's recommends that p-Tau 217 tests be designed with two cut-offs in recognition of signal overlap between diseased and non-diseased subjects. Two cutoffs maximizes the accuracy of the test, but leaves a diagnostic intermediate zone with uncertainty of amyloid status.

Drug Development.

Background: In a 16-week, 91-patient placebo-controlled clinical study in DLB ("AscenD-LB";NCT04001517), neflamapimod improved outcomes on the CDR Sum-of-Boxes (p = 0.023 vs. placebo) and Timed Up and Go test (p = 0.

Analytical and clinical performance of eight Simoa and Lumipulse assays for automated measurement of plasma p-tau181 and p-tau217.

Background: Among the Alzheimer's disease (AD) biomarkers measured in blood, phosphorylated forms of tau (p-tau) have been shown to exhibit a particularly high diagnostic potential. Here, we performed a comprehensive method comparison study, followed by evaluation of the diagnostic performance of eight recent plasma p-tau immunoassays targeting different tau phosphorylation sites, different tau fragments, and that are measured by two distinct platforms.

Methods: We enrolled a cohort of 40 patients with AD at the stage of dementia (AD-dem) characterized by positive CSF A + T + profile, and a control group of 40 cognitively healthy participants (Control), to conduct a comprehensive method comparison for three plasma p-tau181 and five plasma p-tau217 assays run on the Simoa HD-X™ or Lumipulse G600II/G1200 platforms.

Heritability of Alzheimer's disease plasma biomarkers: A nuclear twin family design.

Introduction: Alzheimer's disease (AD) is a highly heritable disease (60%-80%). Amyloid beta (Aβ) 42/40, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) are plasma biomarkers for AD. Clinical biomarker research would be served by an understanding of the sources of variance in these markers.

Performance of plasma p-tau217 and NfL in an unselected memory clinic setting.

Introduction: Plasma phosphorylated tau-217 (p-tau217) and neurofilament light (NfL) can differentiate between different dementias in selected cohorts. We aim to test the discrimination potential of these markers in a real-world cohort.

Methods: We measured p-tau217 (ALZpath) and NfL (Quanterix) in 415 (unselected) consecutive memory clinic patients.

CSF proteins of inflammation, proteolysis and lipid transport define preclinical AD and progression to AD dementia in cognitively unimpaired individuals.

This preclinical AD CSF proteome study identified a panel of 12-CSF markers detecting amyloid positivity and clinical progression to AD with high accuracy; some of these CSF proteins related to immune function, neurotrophic processes, energy metabolism and endolysosomal functioning (e.g., ITGB2, CLEC5A, IGFBP-1, CST3) changed before amyloid positivity is established.

Challenges in the practical implementation of blood biomarkers for Alzheimer's disease.

Blood biomarkers have emerged as accessible, cost-effective, and highly promising tools for advancing the diagnostics of Alzheimer's disease. However, transitioning from cerebrospinal fluid biomarkers to blood biomarkers-eg, to verify amyloid β pathology-requires careful consideration. This Series paper highlights the main challenges in the implementation of blood biomarkers for Alzheimer's disease in different possible contexts of use.

The GFAP proteoform puzzle: How to advance GFAP as a fluid biomarker in neurological diseases.

Glial fibrillary acidic protein (GFAP) is a well-established biomarker of reactive astrogliosis in the central nervous system because of its elevated levels following brain injury and various neurological disorders. The advent of ultra-sensitive methods for measuring low-abundant proteins has significantly enhanced our understanding of GFAP levels in the serum or plasma of patients with diverse neurological diseases. Clinical studies have demonstrated that GFAP holds promise both as a diagnostic and prognostic biomarker, including but not limited to individuals with Alzheimer's disease.

Rationale and design of the BeyeOMARKER study: prospective evaluation of blood- and eye-based biomarkers for early detection of Alzheimer's disease pathology in the eye clinic.

Background: Alzheimer's disease (AD) is a common, complex and multifactorial disease that may require screening across multiple routes of referral to enable early detection and subsequent future implementation of tailored interventions. Blood- and eye-based biomarkers show promise as low-cost, scalable and patient-friendly tools for early AD detection given their ability to provide information on AD pathophysiological changes and manifestations in the retina, respectively. Eye clinics provide an intriguing real-world proof-of-concept setting to evaluate the performance of these potential AD screening tools given the intricate connections between the eye and brain, presumed enrichment for AD pathology in the aging population with eye disorders, and the potential for an accelerated diagnostic pathway for under-recognized patient groups.

Depressive Symptoms and Plasma Markers of Alzheimer's Disease and Neurodegeneration: A Coordinated Meta-Analysis of 8 Cohort Studies.

Background: Depressive symptoms are associated with an increased risk of Alzheimer's disease (AD). There has been a recent emergence in plasma biomarkers for AD pathophysiology, such as amyloid-beta (Aβ) and phosphorylated tau (p-tau), as well as for axonal damage (neurofilament light, NfL) and astrocytic activation (glial fibrillary acidic protein, GFAP). Hypothesizing that depressive symptoms may occur along the AD process, we investigated associations between plasma biomarkers of AD with depressive symptoms in individuals without dementia.

Alzheimer's Disease and Cognitive Decline in Patients with Cardiovascular Diseases Along the Heart-Brain Axis.

Background: We hypothesize that Alzheimer's disease (AD)-related pathology may accelerate cognitive decline in patients with cardiovascular diseases.

Objective: To investigate the association between blood-based biomarkers of AD, astrocyte activation, and neurodegeneration and cognitive decline.

Methods: From the multi-center Heart-Brain study, we included 412 patients with heart failure, carotid occlusive disease or vascular cognitive impairment (age:68.

The use of synaptic biomarkers in cerebrospinal fluid to differentiate behavioral variant of frontotemporal dementia from primary psychiatric disorders and Alzheimer's disease.

Background: Lack of early molecular biomarkers in sporadic behavioral variants of frontotemporal dementia (bvFTD) and its clinical overlap with primary psychiatric disorders (PPD) hampers its diagnostic distinction. Synaptic dysfunction is an early feature in bvFTD and identification of specific biomarkers might improve its diagnostic accuracy. Our goal was to understand the differential diagnostic potential of cerebrospinal fluid (CSF) synaptic biomarkers in bvFTD versus PPD and their specificity towards bvFTD compared with Alzheimer's disease (AD) and controls.