Imaging brain fluid dynamics and waste clearance involving perivascular spaces in cerebral small vessel disease

Alzheimer s & Dementia, Journal Year: 2025, Volume and Issue: 21(4)

Published: April 1, 2025

Abstract Cerebral small vessel disease (SVD) is recognized as a major vascular contributor to cognitive decline, ultimately leading dementia and stroke. While the pathogenesis of SVD remains unclear, emerging evidence suggests that waste clearance involving perivascular space (PVS) – also known glymphatic system dysfunction may play role. Among radiological markers, increased presence dilated PVS marker disruption. Recently developed neuroimaging methods have been proposed indirect measures brain fluid dynamics, but they currently lack formal validation. Here, we provide comprehensive overview latest advancements for assessing including function in SVD. We review mechanisms by which might contribute Finally, argue robust, multimodal, longitudinal studies are essential understanding (involving PVS) establishing diagnostic gold standard. Highlights The majority not visible on MRI, making it crucial understand how why become dilated. origin disruption be multifactorial. BBB likely affect each other, forming vicious cycle, promoting further amyloid beta accumulation. Yet their direct association humans over time studied. Comparative can aid standardization function.

Language: Английский

---

Age-Related Differences in the Choroid Plexus Structural Integrity Are Associated with Changes in Cognition

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

The choroid plexus (CP) plays a critical role in maintaining central nervous system (CNS) homeostasis, producing cerebrospinal fluid, and regulating the entry of specific substances into CNS from blood. CP dysfunction has been implicated various neurological psychiatric disorders, including Alzheimer's disease, Parkinson's multiple sclerosis. This study investigates relationship between structural integrity cognitive decline normative aging, using advanced magnetic resonance imaging techniques, volume, diffusion tensor indices (mean diffusivity, MD, fractional anisotropy, FA) relaxometry metrics (longitudinal, T 1 , transverse, 2 relaxation times). Our results show that diminished microstructural integrity, as reflected by higher MD values, or lower FA is associated with performance processing speed fluency. Notably, measures demonstrated greater sensitivity to than macrostructural measures, i.e. volume. Longitudinal analysis revealed individuals reduced exhibit steeper over time. Furthermore, equation modeling latent variable representing predicts faster overall decline, an effect size comparable age. These findings highlight importance health suggest holistic approach assessing could serve sensitive biomarker for early detection decline. Further research needed elucidate mechanisms underlying explore potential therapeutic implications targeting function prevent treat age-related deficits.

Language: Английский

---

Progranulin deficiency in the brain: the interplay between neuronal and non-neuronal cells

Translational Neurodegeneration, Journal Year: 2025, Volume and Issue: 14(1)

Published: April 16, 2025

Abstract Heterozygous mutations in GRN gene lead to insufficient levels of the progranulin (PGRN) protein, resulting frontotemporal dementia (FTD) with TAR DNA-binding protein 43 (TDP-43) inclusions, classified pathologically as lobar degeneration (FTLD-TDP). Homozygous are exceedingly rare and cause neuronal ceroid lipofuscinosis 11, a lysosomal storage disease onset young adulthood, or an FTD syndrome late-onset manifestations. In this review, we highlight broad spectrum clinical phenotypes associated PGRN deficiency, including primary progressive aphasia behavioral variant dementia. We explore these alongside relevant rodent vitro human models, ranging from induced pluripotent stem cell-derived neural progenitors, neurons, microglia, astrocytes genetically engineered heterotypic organoids containing both neurons astrocytes. summarize advantages limitations models recapitulating main FTLD- hallmarks, highlighting role non-cell-autonomous mechanisms formation TDP-43 pathology, neuroinflammation, neurodegeneration. Data obtained patients’ brain tissues biofluids, parallel single-cell transcriptomics, demonstrate complexity interactions among highly heterogeneous cellular clusters present brain, astrocytes, oligodendroglia, endothelial cells, pericytes. Emerging evidence has revealed that deficiency is cell cluster-specific, often conserved, genetic molecular central nervous system. focus on how distinct populations their dysfunctional crosstalk contribute neurodegeneration neuroinflammation FTD- . Specifically, characterize lipid droplet-accumulating microglia alterations myelin content dysfunction caused by deficiency. Additionally, consider deregulation glia-neuron communication affects exchange organelles such mitochondria, removal excess toxic products aggregates, PGRN-related

Language: Английский

---

Glymphatic system dysfunction in nondialysis-dependent ESRD patients with diabetic kidney disease: associations with clinical characteristics and cognitive function

Renal Failure, Journal Year: 2024, Volume and Issue: 46(2)

Published: Nov. 7, 2024

Objectives To investigate glymphatic function in nondialysis-dependent ESRD (ND-ESRD) patients with diabetic kidney disease (DKD) or non-DKD using the diffusion tensor image analysis along perivascular space (DTI-ALPS) method and choroid plexus (CP) volume to explore associations among DTI-ALPS index, CP volume, clinical characteristics, cognitive function.

Language: Английский

---