Quantitative Physiologic MRI Combined with Feature Engineering for Developing Machine Learning-Based Prediction Models to Distinguish Glioblastomas from Single Brain Metastases.

: The accurate and early distinction of glioblastomas (GBMs) from single brain metastases (BMs) provides a window of opportunity for reframing treatment strategies enabling optimal and timely therapeutic interventions. We sought to leverage physiologically sensitive parameters derived from diffusion tensor imaging (DTI) and dynamic susceptibility contrast (DSC)-perfusion-weighted imaging (PWI) along with machine learning-based methods to distinguish GBMs from single BMs. : Patients with histopathology-confirmed GBMs ( = 62) and BMs ( = 26) and exhibiting contrast-enhancing regions (CERs) underwent 3T anatomical imaging, DTI and DSC-PWI prior to treatment.

Comparison of Plasma p-tau217 and [F]FDG-PET for Identifying Alzheimer Disease in People With Early-Onset or Atypical Dementia.

Background And Objectives: To compare the diagnostic performance of an immunoassay for plasma concentrations of phosphorylated tau (p-tau) 217 with visual assessments of fluorine-18 fluorodeoxyglucose [F]FDG-PET in individuals who meet appropriate use criteria for Alzheimer dementia (AD) biomarker assessments.

Methods: We performed a retrospective analysis of individuals with early-onset (age <65 years at onset) and/or atypical dementia (features other than memory at onset), who were evaluated at a tertiary care memory clinic. All participants underwent measurements of CSF biomarkers (Aβ42, p-tau181, and total tau levels), as well as [F]FDG-PET scans, amyloid-PET scans, and plasma p-tau217 quantifications.

Impact of a national dementia research consortium: The Canadian Consortium on Neurodegeneration in Aging (CCNA).

The Canadian Consortium on Neurodegeneration in Aging (CCNA) was created by the Canadian federal government through its health research funding agency, the Canadian Institutes for Health Research (CIHR), in 2014, as a response to the G7 initiative to fight dementia. Two five-year funding cycles (2014-2019; 2019-2024) have occurred following peer review, and a third cycle (Phase 3) has just begun. A unique construct was mandated, consisting of 20 national teams in Phase I and 19 teams in Phase II (with research topics spanning from basic to clinical science to health resource systems) along with cross-cutting programs to support them.

Hippocampal atrophy over two years in relation to tau, amyloid-β and memory in older adults.

In this longitudinal brain imaging study, we aimed to characterize hippocampal tau accumulation and subfield atrophy relative to cortical amyloid-β and memory performance. We measured tau-PET in regions associated with Braak stages I to VI, global amyloid-PET burden, hippocampal subfield volumes and memory assessments from 173 participants aged 55-85. Eighty-six of these participants were tested again two years later.

Plasma phosphorylated tau181 outperforms [F] fluorodeoxyglucose positron emission tomography in the identification of early Alzheimer disease.

Background And Purpose: This study was undertaken to compare the performance of plasma p-tau181 with that of [F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in the identification of early biological Alzheimer disease (AD).

Methods: We included 533 cognitively impaired participants from the Alzheimer's Disease Neuroimaging Initiative. Participants underwent PET scans, biofluid collection, and cognitive tests.

Insights into the use of biomarkers in clinical trials in Alzheimer's disease.

Biomarkers have been instrumental in population selection and disease monitoring in clinical trials of recently FDA-approved drugs targeting amyloid-β to slow the progression of Alzheimer's disease (AD). As new therapeutic strategies and biomarker techniques emerge, the importance of biomarkers in drug development is growing exponentially. In this emerging landscape, biomarkers are expected to serve a wide range of contexts of use in clinical trials focusing on AD and related dementias.

Cryo-EM structure of Alzheimer's disease tau filaments with PET ligand MK-6240.

Positron Emission Tomography (PET) ligands have advanced Alzheimer's disease (AD) diagnosis and treatment. Using autoradiography and cryo-EM, we identify AD brain tissue with elevated tau burden, purify filaments, and determine the structure of second-generation high avidity PET ligand MK-6240 at 2.31 Å resolution, which bound at a 1:1 ratio within the cleft of tau paired-helical filament (PHF), engaging with glutamine 351, lysine 353, and isoleucine 360.

Modeling the progression of neuropsychiatric symptoms in Alzheimer's disease with PET-based Braak staging.

In Alzheimer's disease (AD), neuropsychiatric symptoms (NPS) correlate with tau deposition in the brain. Here, we investigated the association of PET-based Braak stages with NPS and assessed whether they predict annual changes in NPS. We evaluated 231 individuals in the aging and AD continuum.

PET radiomics-based lymphovascular invasion prediction in lung cancer using multiple segmentation and multi-machine learning algorithms.

The current study aimed to predict lymphovascular invasion (LVI) using multiple machine learning algorithms and multi-segmentation positron emission tomography (PET) radiomics in non-small cell lung cancer (NSCLC) patients, offering new avenues for personalized treatment strategies and improving patient outcomes. One hundred and twenty-six patients with NSCLC were enrolled in this study. Various automated and semi-automated PET image segmentation methods were applied, including Local Active Contour (LAC), Fuzzy-C-mean (FCM), K-means (KM), Watershed, Region Growing (RG), and Iterative thresholding (IT) with different percentages of the threshold.

Glial reactivity is linked to synaptic dysfunction across the aging and Alzheimer's disease spectrum.

Previous studies have shown that glial and neuronal changes may trigger synaptic dysfunction in Alzheimer's disease(AD). However, the link between glial and neuronal markers and synaptic abnormalities in the living brain is poorly understood. Here, we investigated the association between biomarkers of astrocyte and microglial reactivity and synaptic dysfunction in 478 individuals across the aging and AD spectrum from two cohorts with available CSF measures of amyloid-β(Aβ), phosphorylated tau(pTau181), astrocyte reactivity(GFAP), microglial activation(sTREM2), and synaptic biomarkers(GAP43 and neurogranin).

15 Years of Longitudinal Genetic, Clinical, Cognitive, Imaging, and Biochemical Measures in DIAN.

This manuscript describes and summarizes the Dominantly Inherited Alzheimer Network Observational Study (DIAN Obs), highlighting the wealth of longitudinal data, samples, and results from this human cohort study of brain aging and a rare monogenic form of Alzheimer's disease (AD). DIAN Obs is an international collaborative longitudinal study initiated in 2008 with support from the National Institute on Aging (NIA), designed to obtain comprehensive and uniform data on brain biology and function in individuals at risk for autosomal dominant AD (ADAD). ADAD gene mutations in the amyloid protein precursor (), presenilin 1 (), or presenilin 2 () genes are deterministic causes of ADAD, with virtually full penetrance, and a predictable age at symptomatic onset.

Omics-derived biological modules reflect metabolic brain changes in Alzheimer's disease.

Introduction: Brain glucose hypometabolism, indexed by the fluorodeoxyglucose positron emission tomography ([F]FDG-PET) imaging, is a metabolic signature of Alzheimer's disease (AD). However, the underlying biological pathways involved in these metabolic changes remain elusive.

Methods: Here, we integrated [F]FDG-PET images with blood and hippocampal transcriptomic data from cognitively unimpaired (CU, n = 445) and cognitively impaired (CI, n = 749) individuals using modular dimension reduction techniques and voxel-wise linear regression analysis.

Harmonizing tau positron emission tomography in Alzheimer's disease: The CenTauR scale and the joint propagation model.

Introduction: Tau-positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis.

Methods: Using head-to-head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed "CenTauR" [CTR]). JPM is a statistical model that simultaneously models the relationships between head-to-head and anchor point data.

Hormone therapy is associated with lower Alzheimer's disease tau biomarkers in post-menopausal females -evidence from two independent cohorts.

Background: Females represent approximately 70% of the Alzheimer's disease (AD) cases and the literature has proposed a connection between the decreased estrogen levels during menopause and an increased AD risk. Previous investigations have predominantly focused on assessing how hormone therapy (HT) affects the likelihood of AD development and cognitive deterioration. However, as the research framework has shifted toward a biomarker-defined AD and alterations in specific biomarkers could take place years before cognitive decline becomes discernible, it is crucial to examine how HT influences AD biomarkers.

In-vivo neuronal dysfunction by Aβ and tau overlaps with brain-wide inflammatory mechanisms in Alzheimer's disease.

The molecular mechanisms underlying neuronal dysfunction in Alzheimer's disease (AD) remain uncharacterized. Here, we identify genes, molecular pathways and cellular components associated with whole-brain dysregulation caused by amyloid-beta (Aβ) and tau deposits in the living human brain. We obtained resting-state functional MRI (rs-fMRI), Aβ- and tau-PET for 47 cognitively unimpaired and 16 AD participants from the Translational Biomarkers in Aging and Dementia cohort.

Tau follows principal axes of functional and structural brain organization in Alzheimer's disease.

Alzheimer's disease (AD) is a brain network disorder where pathological proteins accumulate through networks and drive cognitive decline. Yet, the role of network connectivity in facilitating this accumulation remains unclear. Using in-vivo multimodal imaging, we show that the distribution of tau and reactive microglia in humans follows spatial patterns of connectivity variation, the so-called gradients of brain organization.

Neuromodulatory subcortical nucleus integrity is associated with white matter microstructure, tauopathy and APOE status.

The neuromodulatory subcortical nuclei within the isodendritic core (IdC) are the earliest sites of tauopathy in Alzheimer's disease (AD). They project broadly throughout the brain's white matter. We investigated the relationship between IdC microstructure and whole-brain white matter microstructure to better understand early neuropathological changes in AD.

Plasma p-tau217 predicts cognitive impairments up to ten years before onset in normal older adults.

Importance: Positron emission tomography (PET) biomarkers are the gold standard for detection of Alzheimer amyloid and tau . Such imaging can identify cognitively unimpaired (CU) individuals who will subsequently develop cognitive impartment (CI). Plasma biomarkers would be more practical than PET or even cerebrospinal fluid (CSF) assays in clinical settings.