Biomarkers.

Background: Patterns of regional atrophy and hypometabolism have been observed in dementia with Lewy bodies (DLB). However, determinants of regional vulnerability to structural and functional neurodegeneration remain largely unexplored. First, we investigated the association between regional gene expression and grey matter volumes in probable DLB patients.

Biomarkers.

Background: Alzheimer's Disease (AD) is a major neurodegenerative disorder characterized by amyloid deposits in brain tissues and representing a continuously increasing global burden in need of disease-modifying therapeutic options. Amyloid beta 1-42 and 1-40 peptides and the amyloid beta 1-42/1-40 ratio are hallmarks of AD and are commonly monitored in Cerebro-Spinal Fluid (CSF) along other AD biomarkers, to support diagnosis and management of AD patients. Over the past few years, blood-based AD biomarkers have emerged as highly relevant and more practical alternatives to CSF biomarkers, and further technical performance characterization of the associated assays would be beneficial to the AD research and medical community.

Biomarkers.

Background: Arterial spin labelling (ASL) is a non-invasive MRI technique for quantifying cerebral blood flow (CBF), used for monitoring changes over the course of a disease or treatment. A crucial parameter in ASL is the post-labelling delay (PLD), determined by the time it takes for blood to travel from the labeling location to the tissue under investigation. Time-encoded ASL (te-ASL) utilizes multiple PLDs for more accurate quantification.

Biomarkers.

Background: A generative model of tau PET was applied to multiple cohorts across the Alzheimer's disease (AD) spectrum, revealing longitudinal changes in tau production and transport. A generalisation of the model accounts for amyloid, tau and neurodegeneration (ATN) interactions and accurately explains longitudinal ATN biomarker data, adding potential for region specific and individualized tracking of ATN biomarkers.

Method: A model of tau spreading and production as measured through PET was developed and applied to longitudinal data from amyloid negative (A-), amyloid positive tau negative (A+T-) and amyloid positive tau positive (A+T+) cohorts from the Alzheimer's disease neuroimaging iniative (ADNI; N = 159) and BioFINDER-2 (BF2; N = 135) datasets.

Biomarkers.

Background: Tau-PET imaging allows in-vivo detection of neurofibrillary tangles. One tau-PET tracer (i.e.

Biomarkers.

Background: Emerging evidence underscores the significant influence of diet on risk for Alzheimer's disease and related dementias (ADRD). In particular, a Western dietary pattern associates with increased risk for ADRD, with proposed mediation via inflammatory mechanisms, among others. Although a Western dietary pattern associates with gut microbiome alterations, it remains unclear whether microbial alterations mediate Western diet-associated inflammation and neurodegeneration.

Biomarkers.

Background: Aggregated TDP-43 is found as the main component of pathological inclusions in amyotrophic lateral sclerosis (ALS), limbic-predominant age-related TDP-43 encephalopathy (LATE), in 50% of patients with frontotemporal dementia (FTD), and is present as co-pathology in other neurodegenerative diseases, including Alzheimer's disease (AD). Biofluid or imaging biomarkers of TDP-43 pathology are currently unavailable. Direct detection of TDP-43 aggregates holds promise for unraveling the pathobiology of disease and for enabling precision medicine approach via improved diagnosis, patient stratification and assessment of therapeutic efficacy in clinical trials in AD and related diseases.

Biomarkers.

Background: Type 2 diabetes mellitus (T2DM) is associated with a greater risk of Alzheimer's disease (AD). Synaptic impairment and protein aggregates have been reported in the brains of T2DM rodent models. Here, we assessed the changes in synaptic vesicle 2A (SV2A), amyloid-β, and tau that are featured pathologies in AD in T2DM rats in vivo.

Biomarkers.

Background: Heavy alcohol consumption is associated with increased risk for Alzheimer's disease and related dementias (ADRD), with mixed evidence suggesting a dose-dependent nonlinear effect of alcohol on ADRD. Potential mechanisms by which alcohol may promote or attenuate brain pathology need further exploration. Although chronic alcohol consumption associates with gut microbiome alterations, it remains unclear whether microbial alterations mediate alcohol-associated neurodegeneration and cognitive decline.

Biomarkers.

Background: The driving mechanisms of structural brain alterations in the earliest stages of Alzheimer's disease (AD) are not well understood. Previous heterogeneous findings in preclinical AD, including subtle atrophy and also increased grey matter (GM) volume, underscore the need for further exploration. This study uses an extensive fluid biomarkers panel to identify pathological drivers behind longitudinal GM changes in cognitively unimpaired (CU) adults.

Biomarkers.

Background: Alzheimer's disease (AD) presents a prolonged asymptomatic phase, providing a significant timeframe for potential intervention. Leveraging this opportunity necessitates the early identification of diagnostic and prognostic biomarkers to detect Alzheimer's pathology during predementia stages. This enables the identification of individuals likely to progress to Alzheimer's-type dementia, allowing them to benefit from targeted disease-modifying therapies.

Biomarkers.

Background: Plasma biomarkers have been increasingly studied in Alzheimer's disease due to their potentially high accessibility, affordability, and low invasiveness. Recent studies have shown that baseline plasma levels are capable of predicting cognitive decline in cognitively unimpaired subjects (CU) and with mild cognitive impairment (MCI). Despite the fact that neuroimaging biomarkers are also strong predictors, it is still unclear how well they perform when compared to plasma biomarkers in predicting cognitive deterioration.

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: Obstructive sleep apnea (OSA) is associated with hypoxia-induced neuronal impairment and dysfunction-key risk factors for the pathogeneses of age-related neurodegenerative diseases such as Alzheimer's disease (AD). This study examined longitudinal associations between OSA severity and CSF biomarkers associated with AD, synaptic dysfunction, and neuroinflammation in a sample of late-middle-aged adults with increased risk for AD.

Method: N=25 cognitively unimpaired adults (64% female, mean age 65.

Biomarkers.

Background: The identification of Alzheimer's disease (AD) pathology at an early stage utilizing plasma biomarkers has attracted significant interest due to its potential for improving global screening programs. Different forms of p-tau measured in plasma, mainly p-tau217, have demonstrated similar diagnostic accuracy when compared to traditional biomarkers. Moreover, plasma biomarkers associated with neuroinflammation and neurodegeneration, namely GFAP and NfL, respectively, have been found to be elevated in patients with amyloidosis and tau accumulation, even though these conditions are not exclusive to AD.

Biomarkers.

Background: Co-pathology between Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB) remains poorly understood but is relevant for trial design. We aimed to compare CSF markers of amyloid, tau, and neurodegeneration (ATN) and α-synuclein between AD, PD, DLB and controls, and investigate the influence of demographical, genetic, and clinical factors on amyloid positivity.

Method: As part of the EPND study, we included 337 individuals with AD, PD, DLB and controls from 6 centers.

Biomarkers.

Background: Substantial variability in tau accumulation patterns in Alzheimer's disease (AD) population has now become accepted. Subtype and Stage Inference (SuStaIn) has distinguished four distinct spatiotemporal trajectories of tau pathology: limbic (S1), medial temporal lobe-sparing (S2), posterior (S3), and lateral temporal (S4). A visual method to validate and identify them is a requirement for their clinical translation.

Biomarkers.

Background: Hippocampal atrophy is an established biomarker of neurodegeneration in Alzheimer's disease, affecting specific subfields (De Flores, La Joie and Chételat, 2015). In this study, we used 7T MRI and advanced diffusion MRI (dMRI) to investigate the relationship between hippocampal subfield volumes and microstructure and assess their sensitivity to cognitive impairment.

Method: Seventeen cognitively impaired (CI; age: 69±8, M/F: 12/5, MMSE: 28) and 22 cognitively unimpaired subjects (CU; age: 62±10, M/F: 6/16) were recruited in the context of the COSCODE project (Ribaldi et al.

Biomarkers.

Background: Lewy body disease (LBD) often co-occurs with Alzheimer's disease neuropathological change (ADNC), which can be detected using plasma pTau181 and pTau217. Few studies have investigated these biomarkers in LBD, nor have studies investigated plasma pTau217 in Parkinson's disease (PD) cognitively normal patients (LBD-CN), or in alpha-synuclein positive (asyn-positive) participants. Furthermore, uncertainties remain regarding LBD-specific cut-points for these biomarkers.

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: Metabotropic glutamate receptor 5 (mGluR5) modulates excitatory glutamatergic synaptic transmission and plays an important role in learning and memory, and in the pathphysiology of Alzheimer's disease (AD). Here, we aimed to assess the alterations of mGluR5 in the hippocampus of AD patients and mouse model, and the association with amyloid pathology.

Method: Immunofluorescence staining was performed on postmortem brain tissue from 35 AD patients and 36 control patients, as well as on the brain tissue slices from 15 months-old 3×Tg and arcAβ mouse models of AD amyloidosis.

Biomarkers.

Background: Blood-based biomarkers of amyloid and tau have been shown to predict AD-dementia risk. Much less is known about their ability to predict risk of Mild Cognitive Impairment (MCI) among cognitively normal individuals. It is also unclear how AD non-specific blood markers of neurodegeneration and neuroinflammation predict MCI and whether they add predictive power above and beyond AD biomarkers.

Biomarkers.

Background: Few studies have examined how a range of potential modifiers may influence the trajectories of Alzheimer's disease (AD) blood biomarkers in those who were cognitively unimpaired when first assessed. This study examined potential modifiers of longitudinal changes in plasma biomarkers, including genetic factors (i.e.

Public Health.

Background: Recent advances in Alzheimer's Disease (AD) disease modifying therapies (DMTs) emphasize the need of an early, timely and accurate diagnosis to initiate treatment and improve patient outcomes. Clinicians must confirm amyloid pathology through cerebrospinal fluid (CSF) testing or amyloid positron emission tomography (PET) scan to qualify patients. As a result, the demand for confirmatory CSF or imaging biomarker testing is predicted to rise significantly.