New Insights into the Development of Donepezil-Based Hybrid and Natural Molecules as Multi-Target Drug Agents for Alzheimer’s Disease Treatment DOI Creative Commons
Violina T. Angelova, Boris Petrov Stoyanov, Rumyana Simeonova

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(22), P. 5314 - 5314

Published: Nov. 11, 2024

Alzheimer's disease (AD) involves a complex pathophysiology with multiple interconnected subpathologies, including protein aggregation, impaired neurotransmission, oxidative stress, and microglia-mediated neuroinflammation. Current treatments, which generally target single subpathology, have failed to modify the disease's progression, providing only temporary symptom relief. Multi-target drugs (MTDs) address several aggregation of pathological proteins. In this review, we cover hybrid molecules published between 2014 2024. We offer an overview strategies employed in drug design approaches that led notable improvements reduced hepatotoxicity. Our aim is insights into potential development new drugs. This highlights multi-target featuring heterocycles

Language: Английский

Blood-brain barrier water permeability across the adult lifespan: a multi-echo ASL study DOI Creative Commons
Beatriz Padrela,

Maksim Slivka,

Markus H. Sneve

et al.

Neurobiology of Aging, Journal Year: 2025, Volume and Issue: 147, P. 176 - 186

Published: Jan. 7, 2025

Language: Английский

Citations

1
Biomarkers of blood–brain barrier and neurovascular unit integrity in human cognitive impairment and dementia DOI Creative Commons
Scott French,

B Meyer,

Juan Carlos Arias

et al.

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(3)

Published: March 1, 2025

Abstract Blood–brain barrier (BBB) dysfunction is recognized as an early step in the development of Alzheimer's disease and related dementias (ADRD). Biomarkers are needed to monitor BBB integrity over time, better understand role neurodegeneration, potentially help define long‐term ADRD risk, effects therapeutics. In this review, we discuss current biomarkers used detect human context cognitive decline dementia. We also promising candidate fluid blood. Highlights permeability occurs during normal aging further exacerbated ADRD. vivo imaging CSF currently setting humans. review blood‐based that may represent dysfunction.

Language: Английский

Citations

1
Navigating Neurodegeneration: Integrating Biomarkers, Neuroinflammation, and Imaging in Parkinson’s, Alzheimer’s, and Motor Neuron Disorders DOI Creative Commons
Masaru Tanaka, Simone Battaglia, Donato Liloia

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(5), P. 1045 - 1045

Published: April 25, 2025

Neurodegenerative diseases represent a daunting global challenge, affecting millions worldwide and imposing significant clinical socioeconomic burdens [...]

Language: Английский

Citations

1
Associations between potential risk factors and blood-brain barrier water permeability in middle-aged and older adults DOI Creative Commons
Mervin Tee, Beatriz Padrela,

Margaux Dupeyron

et al.

Journal of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Background: Blood-brain barrier (BBB) dysfunction is suggested to be a potential mediator between vascular risk factors and cognitive impairment, leading impairment. Objective: To investigate the relationships age, sex, BBB water permeability as well their relationship with cognition. Methods: measure permeability, novel arterial spin labelling MRI technique (ME-ASL) was applied derive time of exchange (Tex), transit (ATT), cerebral blood flow (CBF). The association factors, such body mass index (BMI), pressure (BP), medical history, these parameters were assessed in 144 community-dwelling adults (median age 59 years, 57% females). performance measured by Montreal Cognitive Assessment (MoCA) also assessed. Results: We found that increased BMI significantly associated decreased CBF (β = −0.06). Systolic BP diastolic showed significant associations all ASL parameters; systolic negatively correlated Tex −0.02) −0.01) but positively ATT 0.02). Diastolic −0.03) 0.03). MoCA scores had borderline (OR 1.51) 1.84), which became non-significant after adjusting for confounders. Conclusions: These outcomes underscore using ME-ASL, warranting further research strengthen findings.

Language: Английский

Citations

0
Longitudinal changes of blood-brain barrier and transcytolemmal water exchange permeability in Alzheimer's disease mice: A non-contrast MRI study DOI Creative Commons
Chengjie Xiong, Ziyang Yu,

Yin Yu

et al.

NeuroImage, Journal Year: 2025, Volume and Issue: unknown, P. 121141 - 121141

Published: March 1, 2025

Growing evidence suggests that Alzheimer's disease (AD) has been linked with the dysfunction of glymphatic system. Previous studies were primarily cross-sectional and focused on only one specific component, hindering understanding overall function in AD. We evaluated longitudinal changes multiple components system (blood-brain barrier (BBB) transcytolemmal water exchange (TWE) permeability) AD mice. Five female wild-type four 3 × Tg-AD mice from 5 to 13 months age scanned monthly using two non-contrast MRI techniques, water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST) diffusion-time-dependent kurtosis imaging (tDKI), yielding BBB TWE permeability. Immunostaining was used evaluate tight junction proteins associated structural integrity, aquaporin 4 (AQP4) related TWE, AQP4 perivascular space (PVS) polarization might represent PVS-parenchyma exchange. The relationship between pathology, as measured by amyloid beta (Aβ) tau deposition, also explored. Our results revealed significantly increased hippocampal permeability mouse brains, consistent histological findings reduced upregulated AQP4, which correlated each other can be predictive Aβ deposition. Impaired PVS found In conclusion, altered mice, these vivo validated pathologically, affect waste clearance neurofluid.

Language: Английский

Citations

0
Blood-brain barrier biomarkers modulate the associations of peripheral immunity with Alzheimer’s disease DOI Creative Commons

Jia‐Hui Hou,

Deming Jiang, Min Kyung Chu

et al.

Translational Psychiatry, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 10, 2025

The association between peripheral immunity and Alzheimer's disease (AD) has been increasingly recognized, but the underlying mechanisms are still unclear. We used multiple linear regression models to explore immune biomarkers / blood-brain barrier (BBB)-related AD biomarkers. And we causal mediation analysis with 10,000 bootstrapped iterations investigate functions of BBB-related in mediating associations pathology, cerebral atrophy degree, as well cognitive function. A total 543 participants (38.7% female, mean age 74.8 years) from Disease Neuroimaging Initiative (ADNI) were involved. Neutrophils percent (NEU%), lymphocytes (LYM%), neutrophils (NLR), chemotactic factor-3 (CCL26) significantly associated cerebrospinal fluid (CSF) β-amyloid-42 (Aβ-42), phosphorylated-tau (P-tau), tau (T-tau)/Aβ-42 P-tau/Aβ-42, NEU% pathology mediated by CCL26 (proportion: 18-24%; p < 0.05). NEU%, LYM%, NLR, CCL26, CD40 matrix metalloproteinase-10 (MMP10) whole brain, hippocampal volume, middle temporal lobe (MTL) entorhinal cortex (EC) thickness, degree 7-17%; MMP10 global cognition, executive function, memory immediate recall, delayed function 9-24%; This study suggests that may influence through influencing BBB providing a more robust comprehensive evidence chain for potential role inflammation AD.

Language: Английский

Citations

0
Peripheral immunity affects Alzheimer’s disease by influencing blood-brain barrier function DOI Creative Commons

Jia‐Hui Hou,

Deming Jiang, Min Kyung Chu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 4, 2024

Abstract Background The association between peripheral immunity and Alzheimer's disease (AD) has been increasingly recognized, but the underlying mechanisms are still unclear. This study aims to investigate whether affects AD by influencing blood-brain barrier (BBB) function. Methods Multiple linear regression models were employed explore immune biomarkers [neutrophils percent (NEU%), lymphocytes (LYM%), neutrophils / (NLR)] (including pathology, cerebral atrophy degree, cognitive function). Subsequently, multiple performed BBB-related [chemotactic factor-3 (CCL26), CD40 matrix metalloproteinase-10 (MMP10)] biomarkers. Finally, causal mediation analysis with 10,000 bootstrapped iterations was conducted functions of in mediating associations as well Results A total 543 participants (38.7% female, mean age 74.8 years) from Alzheimer’s Disease Neuroimaging Initiative (ADNI) involved. NEU%, LYM%, NLR, CCL26 significantly associated cerebrospinal fluid (CSF) β-amyloid-42 (Aβ-42), phosphorylated-tau (P-tau), tau (T-tau)/Aβ-42 P-tau/Aβ-42, NEU% pathology mediated (proportion: 18% ~ 24%; p < 0.05). CCL26, MMP10 whole brain, hippocampal volume, middle temporal lobe (MTL) entorhinal cortex (EC) thickness, degree 7% 17%; global cognition, executive function, memory immediate recall, delayed function 9% Conclusions suggests that both deposition, may influence through BBB providing a more robust comprehensive evidence chain for potential role inflammation AD.

Language: Английский

Citations

0
New Insights into the Development of Donepezil-Based Hybrid and Natural Molecules as Multi-Target Drug Agents for Alzheimer’s Disease Treatment DOI Creative Commons
Violina T. Angelova, Boris Petrov Stoyanov, Rumyana Simeonova

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(22), P. 5314 - 5314

Published: Nov. 11, 2024

Alzheimer's disease (AD) involves a complex pathophysiology with multiple interconnected subpathologies, including protein aggregation, impaired neurotransmission, oxidative stress, and microglia-mediated neuroinflammation. Current treatments, which generally target single subpathology, have failed to modify the disease's progression, providing only temporary symptom relief. Multi-target drugs (MTDs) address several aggregation of pathological proteins. In this review, we cover hybrid molecules published between 2014 2024. We offer an overview strategies employed in drug design approaches that led notable improvements reduced hepatotoxicity. Our aim is insights into potential development new drugs. This highlights multi-target featuring heterocycles

Language: Английский

Citations

0