ArticlePloS one2012
Morphological and pathological evolution of the brain microcirculation in aging and Alzheimer's disease.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
What it found
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Who cites it
104 citing papers in PubMed, 178 citations in OpenAlex.
- Microvascular Disease in the Hippocampus in Obstructive Sleep Apnoea.Clocks & sleep · 2026Article
- Choroidal Changes in Cerebral Amyloid Angiopathy Studied by Optical Coherence Tomography Angiography.Translational stroke research · 2026Article
- Cholinergic Basal Forebrain Atrophy Accelerates Cognitive Decline via Cortical Thinning: The Moderating Role of Amyloid-β Pathology in Preclinical Alzheimer's Disease.Research square · 2026Article
- Mitochondrial CaBiomolecules · 2026Review
- Cholinergic basal forebrain atrophy accelerates cognitive decline via cortical thinning: The moderating role of amyloid-β pathology in preclinical Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Article
- CD2AP at the junction of nephropathy and Alzheimer's disease.Molecular neurodegeneration · 2025Review
- The microcirculation, the blood-brain barrier, and the neurovascular unit in health and Alzheimer disease: The aberrant pericyte is a central player.Pharmacological reviews · 2025Review
- Clinical phenotypes of Alzheimer's disease: investigating atrophy patterns and their pathological correlates.Alzheimer's research & therapy · 2025Article
- Gadolinium based contrast agent induced electrical conductivity heterogeneity analysis in the brain of Alzheimer's disease.Scientific reports · 2025Article
- Brain interleukins and Alzheimer's disease.Metabolic brain disease · 2025Review
- Exercise-mediated cerebrovascular repair in Alzheimer's disease: from pathophysiology to therapeutic precision.Frontiers in aging neuroscience · 2025Review
- Impact of Mast Cell Activation on Neurodegeneration: A Potential Role for Gut-Brain Axis andNeurology international · 2024Review
- Challenges and Future Perspectives in Modeling Neurodegenerative Diseases Using Organ-on-a-Chip Technology.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Plant-Derived Zein as an Alternative to Animal-Derived Gelatin for Use as a Tissue Engineering Scaffold.Advanced nanobiomed research · 2024Article
- Super-Resolution Ultrasound Reveals Cerebrovascular Impairment in a Mouse Model of Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Capillary rarefaction: a missing link in renal and cardiovascular disease?Angiogenesis · 2024Review
- An Investigation of the Inflammatory Landscape in the Brain and Bone Marrow of the APP/PS1 Mouse.Journal of Alzheimer's disease reports · 2024Article
- The Expression of Major Facilitator Superfamily Domain-Containing Protein2a (Mfsd2a) and Aquaporin 4 Is Altered in the Retinas of a 5xFAD Mouse Model of Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Proteomic alterations in the brain and blood-brain barrier during brain Aβ accumulation in an APP knock-in mouse model of Alzheimer's disease.Fluids and barriers of the CNS · 2023Article
- Association of Apolipoprotein E4-related Microvascular Disease in the Alzheimer's Disease Hippocampal CA1 Stratum Radiatum.Neuroscience · 2023Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Key pathological hallmarks of Alzheimer's disease (AD), including amyloid plaques, cerebral amyloid angiopathy (CAA) and neurofibrillary tangles do not completely account for cognitive impairment, therefore other factors such as cardiovascular and cerebrovascular pathologies, may contribute to AD. In order to elucidate the microvascular changes that contribute to aging and disease, direct neuropathological staining and immunohistochemistry, were used to quantify the structural integrity of the microvasculature and its innervation in three oldest-old cohorts: 1) nonagenarians with AD and a high amyloid plaque load; 2) nonagenarians with no dementia and a high amyloid plaque load; 3) nonagenarians without dementia or amyloid plaques. In addition, a non-demented (ND) group (average age 71 years) with no amyloid plaques was included for comparison. While gray matter thickness and overall brain mass were reduced in AD compared to ND control groups, overall capillary density was not different. However, degenerated string capillaries were elevated in AD, potentially suggesting greater microvascular "dysfunction" compared to ND groups. Intriguingly, apolipoprotein ε4 carriers had significantly higher string vessel counts relative to non-ε4 carriers. Taken together, these data suggest a concomitant loss of functional capillaries and brain volume in AD subjects. We also demonstrated a trend of decreasing vesicular acetylcholine transporter staining, a marker of cortical cholinergic afferents that contribute to arteriolar vasoregulation, in AD compared to ND control groups, suggesting impaired control of vasodilation in AD subjects. In addition, tyrosine hydroxylase, a marker of noradrenergic vascular innervation, was reduced which may also contribute to a loss of control of vasoconstriction. The data highlight the importance of the brain microcirculation in the pathogenesis and evolution of AD.
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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.