Subregional Biomarkers in FDG PET for Alzheimer’s Diagnosis and Staging: An Interpretable and Explainable model DOI Creative Commons
Ramin Rasi, Albert Güveniş

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 27, 2024

Abstract Objective To investigate the radiomics features of hippocampus and amygdala subregions in FDG-PET images that can best differentiate Mild Cognitive Impairment (MCI), Alzheimer’s Disease (AD), healthy patients. Methods Baseline data from 555 participants ADNI dataset were analyzed, comprising 189 cognitively normal (CN) individuals, 201 with MCI, 165 AD. The segmented based on DKT-Atlas, additional subdivisions guided by probabilistic atlases Freesurfer. Then radiomic (n=120) extracted 38 hippocampal 18 nuclei using PyRadiomics. Various feature selection techniques, including ANOVA, PCA, Chi-square, LASSO, applied alongside nine machine learning classifiers. Results Multi-Layer Perceptron (MLP) model combined LASSO demonstrated excellent classification performance: ROC AUC 0.957 for CN vs. AD, 0.867 MCI 0.782 MCI. Key regions, accessory basal nucleus, presubiculum head, CA4 identified as critical biomarkers. Features GLRLM (Long Run Emphasis) Small Dependence Emphasis (GLDM) showed strong diagnostic potential, reflecting subtle metabolic microstructural changes often preceding anatomical alterations. Conclusion Specific their four found to have a significant role early diagnosis its staging, severity assessment capturing shifts patterns. Furthermore, these offer potential insights into disease’s underlying mechanisms interpretability.

Language: Английский

Alzheimer disease blood biomarkers: considerations for population-level use DOI
Michelle M. Mielke,

Nicole R. Fowler

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(8), P. 495 - 504

Published: June 11, 2024

Language: Английский

Citations

24
Molecular Engineering of a Doubly Quenched Fluorescent Probe Enables Ultrasensitive Detection of Biothiols in Highly Diluted Plasma and High-Fidelity Imaging of Dihydroartemisinin-Induced Ferroptosis DOI
Qin Zeng,

Zhiyang Yuwen,

Lemeng Zhang

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(32), P. 13260 - 13269

Published: Aug. 1, 2024

The occurrence and development of diseases are accompanied by abnormal activity or concentration biomarkers in cells, tissues, blood. However, the insufficient sensitivity accuracy available fluorescence probes hinder precise monitoring associated indexes biological systems, which is generally due to high probe intrinsic false-negative signal caused reactive oxygen species (ROS)-induced decomposition. To resolve these problems, we have engineered a ROS-stable, meso-carboxylate boron dipyrromethene (BODIPY)-based fluorescent probe, displays quite low background doubly quenched combined strategy photoinduced electron transfer (PET) effect "ester-to-carboxylate" conversion. achieved S/N ratio with ultrasensitivity good selectivity toward biothiols, endowing its fast detection capability biothiol level 200×-diluted plasma samples. Using this remarkable distinguishing liver injury from normal even at 80× dilution. Moreover, owing stability ROS, was successfully employed for high-fidelity imaging negative fluctuation nonsmall-cell lung cancer (NSCLC) during dihydroartemisinin-induced ferroptosis. This delicate design suppressing reveals insights into enhancing diseases.

Language: Английский

Citations

7
Alzheimer Disease Blood Biomarkers and Cognition Among Individuals With Diabetes and Overweight or Obesity DOI Creative Commons
Michelle M. Mielke, Joni K. Evans, Rebecca H. Neiberg

et al.

JAMA Network Open, Journal Year: 2025, Volume and Issue: 8(2), P. e2458149 - e2458149

Published: Feb. 6, 2025

Importance Blood-based biomarkers (BBMs) are clinically available to aid in the diagnosis of Alzheimer disease (AD) and AD-related dementias (ADRD), but their association with cognition among older adults specific chronic conditions has not been examined. Objective To longitudinally examine associations between baseline AD ADRD BBMs change participants type 2 diabetes (T2D) overweight or obesity. Design, Setting, Participants The Look AHEAD (Action for Health Diabetes) study was a clinical trial T2D obesity randomized 10-year intensive lifestyle intervention weight loss support education condition. were recruited followed up at 16 sites across US. Enrollment occurred from January 1, 2001, December 31, 2004. primary spanned first 4 years after participants’ enrollment (January 2008, 2011). stopped September 2012 converted an observational study. Blood samples drawn 8 12 later. Cognitive assessments performed 2013, 2014, 2018, 2020. Data present cohort analyzed August 2024. Exposures Baseline 8- 12-year plasma levels amyloid-β (Aβ) 40 , Aβ 42 42/40 ratio, phosphorylated tau 181 (pTau-181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL). Main Outcomes Measures composite z score adjudicated mild cognitive impairment probable dementia. Results mean (SD) age 758 61.5 (6.1) years, 424 [55.9%] female. Mean body mass index 34.8 (5.3). Of participants, 373 385 intervention. Increasing BBM associated any score. NfL (β = −0.032 [SE, 0.013]; P .01) GFAP −0.087 0.025]; < .001), ratio 0.006 0.040]; .88) pTau-181 0.026 .31), worsening function incident had no levels. Conclusions Relevance In this obesity, increasing over time, levels, decline impairment. These results suggest that may be important patient population.

Language: Английский

Citations

0
Plasma p-tau217 and tau-PET predict future cognitive decline among cognitively unimpaired individuals: implications for clinical trials DOI Creative Commons
Rik Ossenkoppele, Gemma Salvadó, Shorena Janelidze

et al.

Nature Aging, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Plasma p-tau217 and tau positron emission tomography (PET) are strong prognostic biomarkers in Alzheimer's disease (AD), but their relative performance predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In a head-to-head comparison study including nine cohorts 1,474 individuals, we show that plasma medial temporal lobe tau-PET signal display similar associations with on global composite test (R2PET = 0.34 versus R2plasma 0.33, Pdifference 0.653) progression to mild impairment (hazard ratio (HR)PET 1.61 (1.48-1.76) HRplasma 1.57 (1.43-1.72), 0.322). Combined PET models were superior the single-biomarker (R2 0.35, P < 0.01). Sequential selection using phosphorylated at threonine 217 (p-tau217) then reduced number of participants required for clinical trial by 94%, compared 76% reduction when alone. Thus, showed CU sequential use enhances screening efficiency preclinical AD trials.

Language: Английский

Citations

0
Antibody-Free Detection of Tau Peptide with l-Arginine-Ligated Polyacrylic Acid-Capped Upconversion Nanoparticle DOI

Merin K. Abraham,

Geneva Indongo,

Greeshma Rajeevan

et al.

ACS Applied Nano Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 29, 2025

Language: Английский

Citations

0
Clinical Application of Blood Biomarkers in Neurodegenerative Diseases—Present and Future Perspectives DOI Open Access

Daria Krawczuk,

Agnieszka Kulczynska‐Przybik, Barbara Mroczko

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8132 - 8132

Published: July 25, 2024

Neurodegenerative diseases are a group of complex characterized by progressive loss neurons and degeneration in different areas the nervous system. They share similar mechanisms, such as neuroinflammation, oxidative stress, mitochondrial injury, resulting neuronal loss. One biggest challenges diagnosing neurodegenerative is their heterogeneity. Clinical symptoms usually present advanced stages disease, thus it essential to find optimal biomarkers that would allow early diagnosis. Due development ultrasensitive methods analyzing proteins other fluids, blood, huge progress has been made field for diseases. The application protein biomarker measurement significantly influenced not only diagnosis but also prognosis, differentiation, new therapies, enables recognition disease individuals with preclinical or mild symptoms. Additionally, introduction biochemical markers into routine clinical practice may improve stratification people higher risk, well an extension well-being since treatment could be started early. In this review, we focus on blood biomarkers, which potentially useful daily medical selected

Language: Английский

Citations

3
In 2024, the amyloid-cascade-hypothesis still remains a working hypothesis, no less but certainly no more DOI Creative Commons
Christian Behl

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Sept. 4, 2024

The amyloid-cascade-hypothesis of the pathogenesis Alzheimer’s disease (AD) was introduced 32 years ago, in 1992. From early on, this clear and straight forward hypothesis received a lot attention, but also substantial criticism. Foremost, there have always been massive doubts that complex age-associated disorder most intricate organ human body, brain, can be explained by linear, one-dimensional cause-and-effect model. amyloid-cascade defines generation, aggregation, deposition amyloid beta peptide as central pathogenic mechanism AD, ultimate trigger disease, and, consequently, key pharmacological target. Certainly, original 1992 version has refined various means, ‘formulating fathers’ followed up with few reappraisals partly very open reflections 2002, 2006, 2009, 2016. However, until today, for supporters hypothesis, initial steps cascade are believed to driven beta—even if now displayed somewhat more elaborate. In light recently published clinical results achieved anti-amyloid antibodies, controversy field about (1) meaningfulness approach, (2) significance clearance peptide, last not least (3) relevance is gaining momentum. This review addresses interesting manifestation well its ups downs over decades.

Language: Английский

Citations

3
Emerging Trends: Neurofilament Biomarkers in Precision Neurology DOI
Priti Sharma, Aditi Giri, Prabhash Nath Tripathi

et al.

Neurochemical Research, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

Language: Английский

Citations

3
Advancements and challenges in mouse models of Alzheimer’s disease DOI
Zhengjiang Qian, Yanjiao Li,

Keqiang Ye

et al.

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

Citations

3
Investigating patient eligibility for anti-amyloid monoclonal antibody treatment of Alzheimer's disease: real-world data from an Austrian psychiatric memory clinic population DOI Creative Commons
Michaela Defrancesco, Elke R. Gizewski, Stephanie Mangesius

et al.

BJPsych Open, Journal Year: 2024, Volume and Issue: 10(5)

Published: Sept. 1, 2024

Pharmacological treatment options for patients with dementia owing to Alzheimer's disease are limited symptomatic therapy. Recently, the US Food and Drug Administration approved monoclonal antibody lecanemab of amyloid-positive mild cognitive impairment (MCI) early Alzheimer´s dementia. European approval is expected in 2024. Data on applicability eligibility anti-amyloid antibodies outside a study population lacking.

Language: Английский

Citations

0