Biomarkers.

Background: The Centiloid method (CL) was introduced as a tracer-independent measure for cortical amyloid load and is now commonly used in Alzheimer's disease (AD) clinical trials. To facilitate its implementation into clinical settings, the AMYPAD consortium set out to integrate existing literature and recent work from the consortium to provide clinical context-of-use recommendations of the Centiloid scale, which has been submitted to the European Medicine Agency for endorsement as a Biomarker Qualification Opinion.

Method: Screening of the literature was performed on the 7/11/23 on PubMed to identify articles mentioning "Centiloid".

Biomarkers.

Background: Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a common neuropathologic finding at advanced age that associates with hippocampal sclerosis (HS) and is often comorbid with AD pathology. Neuroimaging measurements of LATE-NC-associated limbic degeneration have been proposed as indirect biomarkers, but molecular-specific biomarkers for LATE-NC are still lacking. Here we used combined ante-mortem blood and MRI data to study TDP-43 levels in plasma-derived small extracellular vesicles (sEV-TDP-43) and hippocampal volume (HV) in relation to LATE-NC and HS at autopsy.

Biomarkers.

Background: Beyond dementia syndromes, cognitive symptoms are highly prevalent in Parkinson's disease (PD), often manifesting as mild cognitive impairment (MCI). Yet, their detection and characterization remain suboptimal because standard approaches rely on subjective impressions derived from lengthy, univariate tests. Here we introduce a novel approach to detect cognitive symptom severity and identify MCI in PD using fully automated word property analyses on brief verbal fluency tasks.

Biomarkers.

Background: There is a strong link between tau and progression of Alzheimer's disease (AD), necessitating an understanding of tau spreading mechanisms. Prior research, predominantly in typical AD, suggested that tau propagates from epicenters (regions with earliest tau) to functionally connected regions. However, given the constrained spatial heterogeneity of tau in typical AD, validating this connectivity-based tau spreading model in AD variants with distinct tau deposition patterns is crucial.

Biomarkers.

Background: Parkinson's disease (PD) is a debilitating condition that affects millions of people worldwide, yet there are currently no reliable biomarkers for its diagnosis. Alpha-synuclein aggregation is a well-known hallmark of PD pathology, but the behavior and kinetics of these aggregates are poorly understood. To address this gap in knowledge, this study utilized several approaches to evaluate the potential of alpha-synuclein aggregates as potential biomarker for PD.

Biomarkers.

Background: Subjective cognitive decline (SCD), in the absence of objective cognitive impairment, may be the first symptomatic manifestation of Alzheimer's disease (AD). Previous studies have suggested that its combination with amyloid-positivity (Aβ+) may represent stage 2 AD, and is associated with a higher risk of future cognitive decline. Here, we aim to (1) confirm this using the plasma Aβ42/40 ratio, and (2) test whether the addition of plasma phospho-tau181 (ptau, a marker of Aβ and tau pathology) could help refine the prediction of future cognitive decline in SCD patients.

Biomarkers.

Background: With a global ageing population, there is an increasing demand for fast and reliable early diagnosis of individuals. Convolutional neural networks (CNNs) have an immense potential in assisting clinicians in diagnosing dementia. Regional atrophy patterns, which are visible in T1-weighted MRI scans, have been consistently identified by the CNNs with high accuracy.

Role and Prognostic Implications of Venous Outflow Assessment in Acute Ischemic Stroke.

Introduction: The venous outflow profile (VOP) is a crucial yet often overlooked aspect affecting stroke outcomes. It plays a major role in the physiopathology of acute cerebral ischemia, as it accounts for both the upstream arterial collaterals and cerebral microperfusion. This enables it to circumvent the limitations of various arterial collateral evaluation systems, which often fail to consider impaired autoregulation and its impact on cerebral blood flow at the microcirculatory levels.

Biomarkers.

Background: Alzheimer's disease (AD) is a complex disorder with a strong genetic component, yet many genetic risk factors remain unknown. Integrating genome-wide association studies (GWAS) and high-throughput proteomic platforms is a useful strategy to evaluate protein quantitative trait loci (pQTLs) and to detect candidate genes and pathways involved in AD. Due to the novelty of these techniques, the identification of reliable protein measures through a comprehensive quality control is mandatory.

Early-Life Adversity Predicts Markers of Aging-Related Neuroinflammation, Neurodegeneration, and Cognitive Impairment in Women.

Objective: Despite the overwhelming evidence for profound and longstanding effects of early-life stress (ELS) on inflammation, brain structure, and molecular aging, its impact on human brain aging and risk for neurodegenerative disease is poorly understood. We examined the impact of ELS severity in interaction with age on blood-based markers of neuroinflammation and neurodegeneration, brain volumes, and cognitive function in middle-aged women.

Methods: We recruited 179 women (aged 30-60 years) with and without ELS exposure before the onset of puberty.

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: Alzheimer's disease (AD) is associated with substantial synaptic loss potentially due to synaptotoxicity of fibrillar tau, but the association between tau deposition and synaptic loss remains unclear. Based on previous observations that pathology spreads preferentially between closely connected regions, we tested in the current multi-PET tracer study the hypothesis that synaptic loss propagates to regions closely connected to epicenters of high tau accumulation.

Method: We assessed 18F-SynVesT-1 PET as a measure of synaptic vesicle glycoprotein 2A (SV2A), and 18F-flortaucipir tau-PET in fourty-five 18F-florbetapir-PET-positive (Aβ+) subjects with MCI or AD dementia, and 23 cognitivly normal (CN) Aβ- controls.

Biomarkers.

Background: In people with Parkinson's disease (PD), mutations in GBA and LRRK2 are associated with different clinical phenotypes which might be related to differential involvement of the cholinergic system. We aimed to investigate cholinergic basal forebrain (cBF) volume in asymptomatic and symptomatic mutation carriers in comparison to idiopathic PD and healthy controls and associations with cognitive decline.

Method: This study included 149 asymptomatic GBA and 169 asymptomatic LRRK2 mutation carriers, 112 LRRK2 carriers and 60 GBA carriers with PD, 492 idiopathic PD, and 180 healthy controls from the Parkinson's Progression Markers Initiative (PPMI).

Biomarkers.

Background: Differences in task-fMRI activation have recently been found to be related to neuropathological hallmarks of AD. However, the evolution of fMRI-based activation throughout AD disease progression and its relationship with other biomarkers remains elusive. Applying a disease progression model (DPM) to a multicentric cohort with up to four annual task-fMRI visits, we hope to provide a deeper insight into these relationships.

Biomarkers.

Background: The posterior-medial network is crucial for episodic memory. However, the medial temporal lobe (MTL) and posteromedial cortex (PMC) regions are vulnerable to aging and early Alzheimer's disease (AD). Both processes might elicit distinct early functional connectivity (FC) changes which could be detrimental or protective/ compensatory regarding cognition.

Biomarkers.

Background: While some memory decline in old age is "normal", there are some older individuals with maintained high cognitive performance. Using a multimodal approach including neuroimaging, fitness, genetic and questionnaire data (Figure 1A), we aimed to identify factors that are related to successful cognitive aging and whether these differ between sexes.

Method: We analyzed 165 cognitively normal older adults age ≥ 60 years from an ongoing study (SFB1436) (age=71±8years, 43% female).

Biomarkers.

Background: Brain MRI segmentation is required for quantitative PET analysis, in order to derive regional uptake and calculate uptake ratio relative to reference regions. FreeSurfer has been a popular method but is being supplanted by faster and more robust AI-driven methods. The objective of this work is to confirm that the use of Clario's novel AI segmentation method, whose impact was assessed towards various MRI endpoints, is also valid in the context of PET quantification.

Biomarkers.

Background: Alzheimer disease (AD) plasma biomarkers change in the preclinical stage of AD. However, the robustness of the discrimination performance of these biomarkers, as well as their association with longitudinal primary pathology (amyloid and tau) changes, is less understood. We aimed to determine the ability of baseline and longitudinal plasma amyloid-β (Aβ)42/40, p-tau181, GFAP and NfL to detect primary pathology in CU individuals at risk of AD.

Biomarkers.

Background: The human brain integrity relies on the synergistic interplay between neural activity and supporting vascular and metabolic processes throughout life. This relationship, ruled by allostatic mechanisms, regulates brain architecture and activity. White matter hyperintensities (WMH) serve as indicators of the vascular impact on brain structure.

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: Recent technological advancements have revolutionized our approach to healthcare, enabling us to harness the potential of smartphones and wearables to collect data that can be used to characterize Alzheimer's disease (AD) heterogeneity and to develop digital biomarkers. Our focus is to create comprehensive cross-domain digital datasets and establish an infrastructure that allows for seamless data sharing. Central to accelerating the potential of digital biomarkers for more accurate and early detection is privacy-protecting data access, which when combined with deep molecular phenotyping, will enhance our understanding of the biological mechanisms underlying clinical expression.

Biomarkers.

Background: Dementia with Lewy bodies (DLB) is a an α-synucleinopathy characterized by dementia and a combination of parkinsonism, visual hallucinations, fluctuating cognition or REM sleep behaviour disorder. Specific biomarkers for DLB are lacking. DLB-related pattern (DLBRP) is a metabolic network imaging biomarker which expression can be quantified on a single patient basis.

Biomarkers.

Background: Alzheimer's Disease (AD) is often accompanied by neuroinflammation, which manifests prior to significant cognitive decline. Reactive astrocytosis is a hallmark of such inflammation, potentially serving as an early biomarker for AD pathology. Our study employs [18F]fluorodeprenyl-D2 ([18F]F-DED) positron emission tomography (PET) imaging to in vivo quantify astrocytosis comparing AD with healthy controls and examines its assocciation with cognitive deterioration in AD.

Biomarkers.

Background: In Alzheimer's disease (AD), cortical tau aggregation is a strong predictor of cortical brain atrophy as shown by MRI and PET studies, particularly driving the degeneration of neuronal somata in the grey matter. However, tau's physiological role is to stabilize microtubules within axons in the brain's white matter (WM) pathways. Therefore, tau's white-to-grey-matter translocation and aggregation in neurofibrillary tangles close to neuronal somata may induce WM degeneration through destabilization of axonal microtubule integrity.