Biomarkers.

Background: New generation PET scanners achieve superior resolution and sensitivity, but the implications on beta amyloid (Aβ) quantitation are not well understood. The Centiloid (CL) scale (Klunk et al., 2015) was introduced to promote consistent Aβ burden quantification across different positron emission tomography (PET) tracers and quantification pipelines, but was not intended to control for hardware or reconstruction changes.

Biomarkers.

Background: Blood-based biomarkers will be essential for providing clinicians an accessible and cost-effective Alzheimer's disease (AD) screening tool. Elevated levels of two phosphorylated tau biomarkers (pTau181 & pTau217) correlated with amyloid and tau-PET consistent with AD diagnosis. We evaluated the analytical and clinical performance of each biomarkers using two different high-sensitivity methodologies (CLEIA and Simoa®) in a single laboratory to compare the performance of pTau181 and 217 in a clinical (CLIA-certified) laboratory.

Biomarkers.

Background: The MarkVCID consortium was established to address the paucity of biomarkers for vascular contributions to cognitive impairment and dementia (VCID), a leading cause of dementia. Plasma neurofilament light (NfL), a neuroaxonal injury marker elevated in several neurological and neurodegenerative diseases, was selected as one of the first biomarkers to be examined. We performed comprehensive instrumental and clinical validation of the Quanterix Simoa NfL assay using the first MarkVCID cohort.

Biomarkers.

Background: Chronic exposition to stressor factors has been postulated as a cause of structural changes in the brain in the context of dementia. One of these changes can be the fiber integrity loss, that can be measured by diffusion tensor imaging (DTI). We obtained DTI whole brain metrics to relate them with allostatic load in subjects of a chilean cohort of cognitive complaint subjects.

Biomarkers.

Background: The early diagnosis and monitoring of Alzheimer's disease (AD) presents a significant challenge due to its heterogeneous nature, which includes variability in cognitive symptoms, diagnostic test results, and progression rates. This study aims to enhance the understanding of AD progression by integrating neuroimaging metrics with demographic data using a novel machine learning technique.

Method: We used supervised Variational Autoencoders (VAEs), a generative AI method, to analyze high-dimensional neuroimaging data for AD progression, incorporating age and gender as covariates.

Biomarkers.

Background: Peak-width of skeletonized mean diffusivity (PSMD) is an emerging biomarker of cerebral small vessel disease (cSVD)-related vascular contributions to cognitive impairment and dementia (VCID). Higher PSMD values reflect greater white matter microstructural damage, and prior research has related PSMD to sporadic and monogenic forms of cSVD and worse cognitive function. Therefore, we proposed PSMD as a risk stratification biomarker for VCID.

Biomarkers.

Background: Chronic exposure to stress, quantified by allostatic load (AL), has been postulated as a cause of structural brain changes in the context of dementia. White matter hyperintensities (WMH), detected in MRI FLAIR, are a common brain abnormality representing small vessel disease or degenerative changes in the brain. Here, we studied differences in tract-specific WMH volume across three risk levels of AL in Chilean subjects with cognitive complaint, to explore links between chronic stress exposure and prodromal steps of dementia.

Biomarkers.

Background: Cerebral small vessel disease (cSVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although risk factors for cSVD have been identified, little is known about the biological processes and molecular mediators that influence cSVD development and progression.

Methods: Within the Atherosclerosis Risk in Communities (ARIC) study, we used SomaScan Multiplexed Proteomic technology to relate 4,877 plasma proteins to concurrently measured MRI-defined cSVD characteristics, including WMHs, CMHs, and lacunar infarcts, in late-life (n=1508; mean age: 76).

Biomarkers.

Background: Women with suspected coronary microvascular dysfunction (CMD) may be at higher risk of experiencing cognitive decline due to cerebral small vessel disease, a known contributor to Alzheimer's disease and related dementias (ADRD). A potential underlying mechanism that could accelerate this cognitive decline is the accumulation of brain tissue iron, which has been previously linked to changes in brain function potentially caused by oxidative stress and cell death. Therefore, we aim to elucidate whether a similar mechanism could affect women with suspected CMD by investigating the potential role of iron deposition on the brain's functional organization and its effect on cognition using advanced magnetic resonance imaging (MRI).

Biomarkers.

Background: In the context of Alzheimer's disease (AD), blood-based biomarkers have become increasingly important for various clinical purposes, such as screening patients and tracking the progression of the disease. Tau is a protein that stabilizes microtubules in nerve cells. In AD, different isoforms of tau become hyperphosphorylated, leading to the formation of neurofibrillary tangles, which are a key pathological feature of the AD.

Biomarkers.

Background: As new anti-amyloid immunotherapies emerge for Alzheimer's disease (AD), it is clear that early diagnosis of AD pathology is crucial for treatment success. This can be challenging in atypical presentations of AD and, together with our reliance on CSF or PET scans, can, at times, lead to delayed diagnosis. Here, we further explore the possible role of plasma tau phosphorylated at threonine 217 (P-tau217) for the detection of primary AD or AD co-pathology when frontotemporal dementia spectrum disorders are the main clinical presentation.

Biomarkers.

Background: A key characteristic of Alzheimer's disease (AD) is cerebral aggregation of tau. These aggregates can be quantified and localized with positron emission tomography (PET), which improves the diagnostic and prognostic work-up of AD. However, tau-PET is expensive and not available in clinical settings globally.

Biomarkers.

Background: Alzheimer's disease (AD) blood biomarkers alone can detect amyloid-β (Aβ) pathology in cognitively unimpaired (CU) individuals. We assessed whether combining different plasma biomarkers improves the detection of Aβ-positivity and identifies rapid amyloid deposition in CU individuals.

Method: CU participants from the ALFA+ cohort were included.

Biomarkers.

Background: The research on Alzheimer's disease (AD) has substantially advanced in relation to plasma biomarkers, such as pTau217, for the detection of amyloid (Aβ) pathology which identify, with high accuracy, individuals in the AD biological continuum. However, as these biomarkers become abnormal very early in the disease, biomarkers identifying more advanced disease stages and proxying pathophysiological processes beyond amyloidosis are still needed. Therefore, we have conducted a proteomic study, on plasma and CSF, aiming at identifying proteins reflecting pathological changes in AD.

Biomarkers.

Background: Tau PET is instrumental in tracking the longitudinal progression of Alzheimer's disease (AD). F-MK6240 is a high affinity tracer targeting the 3R/4R paired helical filaments of tau in AD. We aimed to evaluate the early phase of the natural progression of tau accumulation using F-MK6240.

Biomarkers.

Background: The performance of blood-based phosphorylated tau (pTau) immunoassays to detect asymptomatic Alzheimer's disease (AD) has important implications for therapeutic trials. pTau217 is often recommended as the preferred epitope due to its high fold changes in AD. The current study investigates the ability of a novel pTau217 assay to predict the dynamic phase of amyloid-β (Aβ) accumulation in comparison to the best-performing pTau181 assay.

Biomarkers.

Background: Memory decline in late life is a common hallmark of aging, yet SuperAgers are individuals age 80+ with episodic memory performances at least as good as cognitively average 50-to-60-year-olds. Recent work, combining anatomical and functional MRI, has shown the precise boundaries of large-scale resting state networks vary at the individual level. Further, the use of person-specific rather than standard parcellations has led to more behaviorally meaningful associations, and has not been explored in SuperAgers.

Biomarkers.

Background: Alzheimer's disease (AD) is an uncurable, heterogeneous, and molecular complex neurodegenerative disease. Emerging evidence indicates that furin could play an essential role in the pathogenesis of neurodegenerative disorders. Furin participates in the proteolytic maturation and processing of large numbers of prohormones and proproteins, which among others play crucial roles in neuronal survival, axon growth, dendritic development, synaptogenesis, neurodegeneration, and inflammation.

Biomarkers.

Background: Plasma biomarkers for Alzheimer's disease (AD) have demonstrated their accuracy as diagnostic tools, suggesting their impending integration into clinical practice. Medical comorbidities might not only affect AD pathological burdens but also cause variability of plasma biomarkers by affecting their transfer via blood brain barriers. In the present study, we aimed to determine which comorbidities might affect plasma biomarkers with (real effects) or without (biological variability) AD pathological burdens measured by β-amyloid (Aβ) uptakes on PET.

Biomarkers.

Background: To date, all computerised perivascular spaces (PVS) quantification methods require case-wise, imaging modality, or study-specific parameter adjustments, and suffer from generalisability problems in clinical settings, and misdetection of other cerebral small vessel disease (CSVD) markers. We propose a deep learning-based PVS detection method to overcome these issues. We compare our proposal on magnetic resonance imaging data of CSVD participants against the performance of the Frangi filter.

Biomarkers.

Background: Emerging evidence underscores the importance of neuroinflammation in the progression of Alzheimer's disease (AD) pathophysiology. Recent studies indicate the involvement of the inflammatory mechanisms both in amyloid- β (Aβ) and tau deposition in the brain. Nevertheless, due to the complexity of the immune responses and the intricate interplay between the peripheral and the central nervous systems, identifying biomarkers that reflect the brain´s inflammatory state in AD has been a challenge.

Biomarkers.

Background: Epigenetic clocks are biomarkers of biological age based on DNA methylation (DNAm) patterns and are widely used as predictors of health and aging outcomes. Multiple epigenetic clocks have been developed and reflect different aspects of the multidimensional aging process, above and beyond chronological age. To date, no study has examined the relationship of epigenetic aging with circulating biomarkers of Alzheimer's Disease (AD).

Biomarkers.

Background: For medical purposes, amyloid-beta (Aβ) and tau biomarkers are typically dichotomized into positive (+) and negative (-) status to define individuals with Alzheimer's disease (AD) pathology. Nevertheless, such AD proteinopathies start accumulating years before reaching clinically-defined abnormality thresholds. We examined longitudinal change in PET Aβ and tau in cognitively unimpaired (CU) individuals; then we explored their baseline plasma levels and demographic characteristics.

Biomarkers.

Background: Single molecule array (Simoa) technology enables the detection of Alzheimer's disease (AD) neuropathology in blood. This study compared cross-sectional biomarker profiles for participants from the New Zealand-Dementia Prevention Research Clinics (NZ-DPRCs) who spanned the continuum from healthy older adults to a clinical diagnosis of AD.

Method: NZ-DPRC participants were clinically classified as cognitively unimpaired adults (CU, n=34), subjective cognitive decline (SCD, n=65), non-amnestic mild cognitive impairment (single and multi-domain, non-aMCI, n= 23), amnestic MCI (single and multi-domain, aMCI, n=104), and AD (n=27).