ArticleMolecular neurodegeneration2014
Vascular and parenchymal amyloid pathology in an Alzheimer disease knock-in mouse model: interplay with cerebral blood flow.
Article in Molecular neurodegeneration, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
64 citing papers in PubMed, 87 citations in OpenAlex.
- Cerebral Intramural Cells: A Missing Cellular Link Between Vascular Aging and Alzheimer's Disease.International journal of molecular sciences · 2026Review
- EndMT in vascular cognitive impairment and dementia: mechanisms, evidence gaps, and therapeutic opportunities.Molecular medicine (Cambridge, Mass.) · 2026Review
- Multi-parametric longitudinal imaging of cerebral biomarkers in a rodent model of Alzheimer's disease.Photoacoustics · 2026Article
- Differential Left and Right Carotid Artery Blood Flow and Altered Hippocampal Mitochondrial Function After Transverse Aortic Constriction in Aging Rats.Journal of the American Heart Association · 2026Article
- Associations between cerebral blood transit time, amyloid-β pathology and cognitive decline in non-demented older adults.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Blood-Brain Barrier (BBB) Dysfunction in CNS Diseases: Paying Attention to Pericytes.CNS neuroscience & therapeutics · 2025Review
- Hippocampal vascularization pattern and cerebral blood flow cooperatively modulate hippocampal tolerable amount of Aβ deposition in the occurrence of MCI.Fluids and barriers of the CNS · 2025Article
- Hypotension with neurovascular changes and cognitive dysfunction: An epidemiological, pathobiological, and treatment review.Chinese medical journal · 2025Review
- Non-invasive volumetric ultrasound localization microscopy detects vascular changes in mice with Alzheimer's disease.Theranostics · 2025Article
- A nomogram based on coagulation markers for predicting meige syndrome risk.Frontiers in aging neuroscience · 2025Article
- Inhibiting CaNature neuroscience · 2024Article
- Loss of Direct Vascular Contact to Astrocytes in the Hippocampus as an Initial Event in Alzheimer's Disease. Evidence from Patients, In Vivo and In Vitro Experimental Models.Molecular neurobiology · 2024Article
- Alzheimer's disease pathophysiology in the Retina.Progress in retinal and eye research · 2024Review
- Alzheimer's Disease from Modeling to Mechanism Research.Advances in neurobiology · 2024Review
- Impact of thyroid hormone perturbations in adult mice: brain weight and blood vessel changes, gene expression variation, and neurobehavioral outcomes.Neurobiology of aging · 2023Article
- Emerging Links between Cerebral Blood Flow Regulation and Cognitive Decline: A Role for Brain Microvascular Pericytes.Aging and disease · 2023Review
- Direct Oral Anticoagulants (DOACs) for Therapeutic Targeting of Thrombin, a Key Mediator of Cerebrovascular and Neuronal Dysfunction in Alzheimer's Disease.Biomedicines · 2022Review
- Chronic cerebral hypoperfusion and blood-brain barrier disruption in uninjured brain areas of rhesus monkeys subjected to transient ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Recent Advances in the Modeling of Alzheimer's Disease.Frontiers in neuroscience · 2022Review
- Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundAccumulation and deposition of β-amyloid peptides (Aβ) in the brain is a central event in the pathogenesis of Alzheimer's disease (AD). Besides the parenchymal pathology, Aβ is known to undergo active transport across the blood-brain barrier and cerebral amyloid angiopathy (CAA) is a prominent feature in the majority of AD. Although impaired cerebral blood flow (CBF) has been implicated in faulty Aβ transport and clearance, and cerebral hypoperfusion can exist in the pre-clinical phase of Alzheimer's disease (AD), it is still unclear whether it is one of the causal factors for AD pathogenesis, or an early consequence of a multi-factor condition that would lead to AD at late stage. To study the potential interaction between faulty CBF and amyloid accumulation in clinical-relevant situation, we generated a new amyloid precursor protein (APP) knock-in allele that expresses humanized Aβ and a Dutch mutation in addition to Swedish/London mutations and compared this line with an equivalent knock-in line but in the absence of the Dutch mutation, both crossed onto the PS1M146V knock-in background.
resultsIntroduction of the Dutch mutation results in robust CAA and parenchymal Aβ pathology, age-dependent reduction of spatial learning and memory deficits, and CBF reduction as detected by fMRI. Direct manipulation of CBF by transverse aortic constriction surgery on the left common carotid artery caused differential changes in CBF in the anterior and middle region of the cortex, where it is reduced on the left side and increased on the right side. However these perturbations in CBF resulted in the same effect: both significantly exacerbate CAA and amyloid pathology.
conclusionsOur study reveals a direct and positive link between vascular and parenchymal Aβ; both can be modulated by CBF. The new APP knock-in mouse model recapitulates many symptoms of AD including progressive vascular and parenchymal Aβ pathology and behavioral deficits in the absence of APP overexpression.
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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.