ArticleFluids and barriers of the CNS2019
Pathological mitochondria in neurons and perivascular astrocytic endfeet of idiopathic normal pressure hydrocephalus patients.
Article in Fluids and barriers of the CNS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
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Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Associations between the brain glymphatic system and mitochondrial (dys)function: a systematic review.Frontiers in neuroscience · 2025Pooled it
- Role of aquaporins in hydrocephalus: what do we know and where do we stand? A systematic review.Journal of neurology · 2021Pooled it
- CSF Aquaporin-4 levels in controls and in idiopathic normal pressure hydrocephalus before and after shunt surgery.Fluids and barriers of the CNS · 2026Article
- Article
- From the past to the present: evolving theories in the pathophysiology of normal pressure hydrocephalus.Journal of neurology, neurosurgery, and psychiatry · 2026Review
- Dynamics of brain valves: ostensible rectification mechanisms for cerebrospinal fluid flow.Journal of the Royal Society, Interface · 2025Article
- Causal relationship between Baff-R expression and normal pressure hydrocephalus: insights from Mendelian randomization analysis.BMC neurology · 2025Article
- Is cerebral small vessel disease a central nervous system interstitial fluidopathy?IBRO neuroscience reports · 2024Article
- Interstitial Fluidopathy of the Central Nervous System: An Umbrella Term for Disorders with Impaired Neurofluid Dynamics.Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine · 2024Article
- Novel therapeutic strategies targeting mitochondria as a gateway in neurodegeneration.Neural regeneration research · 2023Review
- Assessment of factors influencing glymphatic activity and implications for clinical medicine.Frontiers in neurology · 2023Review
- Focus on the role of mitochondria in NLRP3 inflammasome activation: A prospective target for the treatment of ischemic stroke (Review).International journal of molecular medicine · 2022Review
- Glymphatic imaging and modulation of the optic nerve.Neural regeneration research · 2022Article
- Aquaporin-4 and Cognitive Disorders.Aging and disease · 2022Review
- The pathogenesis of idiopathic normal pressure hydrocephalus based on the understanding of AQP1 and AQP4.Frontiers in molecular neuroscience · 2022Review
- Intrathecal Contrast-Enhanced Magnetic Resonance Imaging of Cerebrospinal Fluid Dynamics and Glymphatic Enhancement in Idiopathic Normal Pressure Hydrocephalus.Frontiers in neurology · 2022Article
- A New Perspective on the Pathophysiology of Idiopathic Intracranial Hypertension: Role of the Glia-Neuro-Vascular Interface.Frontiers in molecular neuroscience · 2022Article
- Cellular changes at the glia-neuro-vascular interface in definite idiopathic normal pressure hydrocephalus.Frontiers in cellular neuroscience · 2022Article
- Novel therapeutic modulators of astrocytes for hydrocephalus.Frontiers in molecular neuroscience · 2022Review
- Increased occurrence of pathological mitochondria in astrocytic perivascular endfoot processes and neurons of idiopathic intracranial hypertension.Journal of neuroscience research · 2021Observational
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundA growing body of evidence suggests that the accumulation of amyloid-β and tau (HPτ) in the brain of patients with the dementia subtype idiopathic normal pressure hydrocephalus (iNPH) is associated with delayed extravascular clearance of metabolic waste. Whether also clearance of intracellular debris is affected in these patients needs to be examined. Hypothetically, defective extra- and intra-cellular clearance of metabolites may be instrumental in the neurodegeneration and dementia characterizing iNPH. This study explores whether iNPH is associated with altered mitochondria phenotype in neurons and astrocytes.
methodsCortical brain biopsies of 9 reference (REF) individuals and 30 iNPH patients were analyzed for subcellular distribution and morphology of mitochondria using transmission electron microscopy. In neuronal soma of REF and iNPH patients, we identified normal, pathological and clustered mitochondria, mitochondria-endoplasmic reticulum contact sites and autophagic vacuoles. We also differentiated normal and pathological mitochondria in pre- and post-synaptic nerve terminals, as well as in astrocytic endfoot processes towards vessels.
resultsWe found a high prevalence of pathological mitochondria in neuronal soma and pre- and post-synaptic terminals, as well as increased mitochondrial clustering, and altered number of mitochondria-endoplasmic reticulum contact sites in iNPH. Non-fused autophagic vacuoles were more abundant in neuronal soma of iNPH patients, suggestive of cellular clearance failure. Moreover, the length of postsynaptic densities was reduced in iNPH, potentially related to reduced synaptic activity. In astrocytic endfoot processes, we also found increased number, area and area fraction of pathological mitochondria in iNPH patients. The proportion of pathological mitochondria correlated significantly with increasing degree of astrogliosis and reduced perivascular expression of aquaporin-4 (AQP4), assessed by light microscopy immunohistochemistry.
conclusionOur results provide evidence of mitochondrial pathology and signs of impaired cellular clearance in iNPH patients. The results indicate that iNPH is a neurodegenerative disease with close similarity to Alzheimer's disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.