Alzheimer's disease neuropathology and its estimation with fluid and imaging biomarkers DOI Creative Commons
Dietmar Rudolf Thal, Koen Poesen, Rik Vandenberghe

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 14, 2025

Abstract Alzheimer’s disease (AD) is neuropathologically characterized by the extracellular deposition of amyloid-β peptide (Aβ) and intraneuronal accumulation abnormal phosphorylated tau (τ)-protein (p-τ). Most frequently, these hallmark lesions are accompanied other co-pathologies in brain that may contribute to cognitive impairment, such as vascular lesions, transactive-response DNA-binding protein 43 (TDP-43), and/or α-synuclein (αSyn) aggregates. To estimate extent AD patients, several biomarkers have been developed. Specific tracers target visualize Aβ plaques, p-τ αSyn pathology or inflammation positron emission tomography. In addition imaging biomarkers, cerebrospinal fluid, blood-based biomarker assays reflecting AD-specific non-specific processes either already clinical use development. this review, we will introduce pathological brain, related discuss what respective determined at post-mortem histopathological analysis. It became evident initial stages plaque not detected with currently available biomarkers. Interestingly, precedes deposition, especially beginning when unable detect it. Later, takes lead accelerates pathology, fitting well known evolution measures over time. Some still lack clinically established today, TDP-43 cortical microinfarcts. summary, specific for AD-related pathologies allow accurate diagnosis based on pathobiological parameters. Although current excellent pathologies, they fail which analysis required. Accordingly, neuropathological studies remain essential understand development early stages. Moreover, there an urgent need co-pathologies, limbic predominant, age-related encephalopathy-related modify interacting p-τ. Novel approaches vesicle-based cryptic RNA/peptides help better future.

Language: Английский

The impact of exercise on blood-based biomarkers of Alzheimer’s disease in cognitively unimpaired older adults DOI Creative Commons
Kelsey R. Sewell, Stephanie R. Rainey‐Smith, Steve Pedrini

et al.

GeroScience, Journal Year: 2024, Volume and Issue: 46(6), P. 5911 - 5923

Published: March 15, 2024

Abstract Physical activity is a promising preventative strategy for Alzheimer’s disease: it associated with lower dementia risk, better cognition, greater brain volume and beta-amyloid. Blood-based biomarkers have emerged as low-cost, non-invasive detecting preclinical disease, however, there limited literature examining the effect of exercise (a structured form physical activity) on blood-based biomarkers. The current study investigated influence 6-month intervention levels plasma beta-amyloid (Aβ42 , Aβ40, Aβ42/40), phosphorylated tau (p-tau181), glial fibrillary acidic protein (GFAP) neurofilament light (NfL) chain in cognitively unimpaired older adults, secondary aim, whether related to cognition. Ninety-nine community-dwelling adults (69.1 ± 5.2) were allocated an inactive control, or moderate high intensity groups where they cycled twice weekly six months. At baseline months (post-intervention), fasted blood was collected analysed using single molecule array (SIMOA) assays, cognition assessed. Results demonstrated no change any biomarker from pre- post-intervention. baseline, higher NfL poorer ( β = -0.33, SE 0.13, adjusted p .042). Exploratory analyses indicated cardiorespiratory fitness GFAP apolipoprotein E APOE ) ε4 non-carriers compared carriers (NfL, -0.43, 0.19, .029; GFAP, -0.41, 0.20, .044), though this association mediated by body mass index (BMI). These results highlight importance considering BMI analysis biomarkers, especially when investigating differences between non-carriers. Our also indicate that longer follow-up periods may be required observe exercise-induced

Language: Английский

Citations

12
Clinical and diagnostic implications of Alzheimer’s disease copathology in Lewy body disease DOI
Lorenzo Barba, Samir Abu‐Rumeileh, Henryk Barthel

et al.

Brain, Journal Year: 2024, Volume and Issue: 147(10), P. 3325 - 3343

Published: July 11, 2024

Concomitant Alzheimer's disease (AD) pathology is a frequent event in the context of Lewy body (LBD), occurring approximately half all cases. Evidence shows that LBD patients with AD copathology show an accelerated course, greater risk cognitive decline and overall poorer prognosis. However, LBD-AD cases may heterogeneous motor non-motor phenotypes higher dementia and, consequently, be not rarely misdiagnosed. In this review, we summarize current understanding by discussing synergistic effects neuropathological changes their clinical relevance. Furthermore, provide extensive overview neuroimaging fluid biomarkers under assessment for use possible diagnostic prognostic values. can predicted vivo means CSF, MRI PET markers, whereas most promising technique to date identifying different biological tissues α-synuclein seed amplification assay. Pathological imaging CSF are associated likelihood but do always mirror severity as pure AD. Implementing blood-based might allow faster screening copathology, thus improving sensitivity LBD-AD. Finally, discuss literature on novel candidate being exploited investigate other aspects neurodegeneration, such neuroaxonal injury, glial activation synaptic dysfunction. The thorough characterization should taken into account when considering differential diagnoses syndromes, evaluation individual level, guide symptomatic disease-modifying therapies.

Language: Английский

Citations

10
Electrochemical Biosensor for Point-of-Care Testing of Low-Abundance Biomarkers of Neurological Diseases DOI
Ziyue Huang, Lei Zhang,

Yanzhi Dou

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(25), P. 10332 - 10340

Published: June 12, 2024

The neurofilament protein light chain (NEFL) is a potential biomarker of neurodegenerative diseases, and interleukin-6 (IL-6) also closely related to neuroinflammation. Especially, NEFL IL-6 are the two most low-abundance known markers neurological making their detection very important for early diagnosis prognosis prediction such kinds diseases. Nevertheless, quantitative low concentrations in serum remains quite difficult, especially point-of-care test (POCT). Herein, we developed portable, sensitive electrochemical biosensor combined with smartphones that can be applied multiple scenarios IL-6, meeting need POCT. We used double-antibody sandwich configuration polyenzyme-catalyzed signal amplification improve sensitivity sera. could detect as 5.22 pg/mL 3.69 6 μL within 2 h, demonstrating this worked well systems. Results showed its superior capabilities over those high-sensitivity ELISA samples. Importantly, by detecting sera, POCT model all biomarkers it possible mass screening patients

Language: Английский

Citations

9
Serum biomarkers as prognostic markers for Alzheimer's disease in a clinical setting DOI Creative Commons
Steffi De Meyer, Elena R. Blujdea, Jolien Schaeverbeke

et al.

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Journal Year: 2025, Volume and Issue: 17(1)

Published: Jan. 1, 2025

Language: Английский

Citations

1
Alzheimer's disease neuropathology and its estimation with fluid and imaging biomarkers DOI Creative Commons
Dietmar Rudolf Thal, Koen Poesen, Rik Vandenberghe

et al.

Molecular Neurodegeneration, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 14, 2025

Abstract Alzheimer’s disease (AD) is neuropathologically characterized by the extracellular deposition of amyloid-β peptide (Aβ) and intraneuronal accumulation abnormal phosphorylated tau (τ)-protein (p-τ). Most frequently, these hallmark lesions are accompanied other co-pathologies in brain that may contribute to cognitive impairment, such as vascular lesions, transactive-response DNA-binding protein 43 (TDP-43), and/or α-synuclein (αSyn) aggregates. To estimate extent AD patients, several biomarkers have been developed. Specific tracers target visualize Aβ plaques, p-τ αSyn pathology or inflammation positron emission tomography. In addition imaging biomarkers, cerebrospinal fluid, blood-based biomarker assays reflecting AD-specific non-specific processes either already clinical use development. this review, we will introduce pathological brain, related discuss what respective determined at post-mortem histopathological analysis. It became evident initial stages plaque not detected with currently available biomarkers. Interestingly, precedes deposition, especially beginning when unable detect it. Later, takes lead accelerates pathology, fitting well known evolution measures over time. Some still lack clinically established today, TDP-43 cortical microinfarcts. summary, specific for AD-related pathologies allow accurate diagnosis based on pathobiological parameters. Although current excellent pathologies, they fail which analysis required. Accordingly, neuropathological studies remain essential understand development early stages. Moreover, there an urgent need co-pathologies, limbic predominant, age-related encephalopathy-related modify interacting p-τ. Novel approaches vesicle-based cryptic RNA/peptides help better future.

Language: Английский

Citations

1