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).

Biomarkers.

Background: Tau phosphorylated at position 217 (pTau217) is considered to have the highest accuracy in identifying Alzheimer's disease (AD) pathology using blood. We describe a multi-cohort evaluation of the Simoa ALZpath pTau217 assay for the prediction of amyloid status in combination with additional blood-based AD biomarkers (GFAP, pTau181, etc.), as well as comparisons between histopathological and PET based amyloid measurements.

Biomarkers.

Background: Early autonomic function changes in Alzheimer's disease (AD) may represent a biomarker for early affective changes in prodromal disease. We report preliminary differences in metrics of heart rate variability (HRV) before and during routine cognitive testing.

Method: We enrolled 50 participants from the Wake Forest Alzheimer's Disease Research Center to wear continuous ECG devices during their visit to assess time and frequency domain based metrics of HRV over 5 minutes at rest and during cognitive testing.

Biomarkers.

Background: Clinicians and researchers utilize neuroimaging (NI) biomarkers of Alzheimer's disease (AD) at an increasing rate. It is crucial that we determine whether these biomarkers generalize to underrepresented populations, particularly Black Americans (BAs), as they are 64% more likely as white individuals to develop AD. BAs may exhibit unique AD biomarker profiles across disease states, including NI biomarkers.

Biomarkers.

Background: White matter (WM) hyperintensities are bright areas on T2 MRI that reflect increased interstitial fluid caused by demyelination and axonal loss; these tissue alterations have been associated with cognitive impairment. Previous in-vivo studies have suggested that the underlying pathogenesis for WM changes differs between the anterior and posterior brain, with cerebrovascular disease contributing more to anterior WM lesions and neurodegenerative processes contributing more to posterior WM lesions.

Method: Periventricular (PV) and deep subcortical (DS) WM hyperintensities both in the anterior and posterior portions of the brain were identified using postmortem T2 MRI of cerebral hemispheres from the Biggs Institute Brain Bank (Figure 1) in 7 Alzheimer's Disease patients (four male, three female, average age 75).

Biomarkers.

Background: Traditionally linked to essential physiological functions, the brainstem is now acknowledged for its role in cognition and dementia. Abnormal tau protein accumulation starts in the brainstem. Late life brainstem volume at baseline also predicts later Alzheimer's Disease conversion.

Biomarkers.

Background: Plasma biomarkers have emerged as a promising tool to detect the presence of Alzheimer's disease (AD) when cognitive symptoms have not yet emerged. However, there is also a pressing need to detect and track subtle cognitive change at the preclinical stage of AD for population screening purposes and to monitor disease progression at scale. A potential solution is remote cognitive assessment, yet it is still not extensively employed.

Biomarkers.

Background: Plasma pTau217 (tau phosphorylated at threonine 217) assays will expand access to screening for Alzheimer's disease (AD). However, clinical interpretation is not well-established, particularly during the preclinical window when interventions may be most effective. Using plasma samples from primarily late-midlife, cognitively unimpaired Wisconsin Registry for Alzheimer's Prevention (WRAP) and Wisconsin Alzheimer's Disease Center (WADRC) participants, we investigated pTau217 agreement with amyloid and tau PET then compared trajectories between participants grouped by baseline pTau217.

Biomarkers.

Background: Different patterns of atrophy exist in the dementia stage of AD. However, little is known about the heterogeneity of atrophy patterns and the mechanisms that drive subsequent propagation of the disease in the preclinical stages.

Method: From the AMYPAD-PNHS cohort, we included a total of 1323 non-demented individuals, including 1094 amyloid-negative, and 229 amyloid-positive participants (Table 1).

Biomarkers.

Background: Alzheimer's disease (AD) and related dementias can have long preclinical phases; thus, midlife intervention and prevention methods could prove efficacious. Multiple health-related lifestyle factors have been associated with risk for AD. However, research on lifestyle factors has focused on clinical outcomes such as cognitive decline, mild cognitive impairment and/or AD dementia; their associations with potential early changes in cerebrospinal fluid (CSF) biomarkers are less understood.

Electrophysiological Signatures of Alpha Coma.

Purpose: Recent research on quantitative EEG in coma has proposed several metrics correlating with consciousness level. However, the heterogeneous nature of coma can challenge the generalizability of these measures. This study investigates alpha-coma, an electroclinical pattern characterized by a widespread, nonreactive alpha rhythm often linked to poor outcomes.