ArticleAnnals of clinical and translational neurology2014
Phosphodiesterase III inhibitor promotes drainage of cerebrovascular β-amyloid.
Article in Annals of clinical and translational neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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Who cites it
56 citing papers in PubMed, 95 citations in OpenAlex.
- Efficacy and Safety of Cilostazol in Mild Cognitive Impairment: A Randomized Clinical Trial.JAMA network open · 2023Trial
- Cerebral Intramural Cells: A Missing Cellular Link Between Vascular Aging and Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Deciphering the role of APOE in cerebral amyloid angiopathy: from genetic insights to therapeutic horizons.Annals of medicine · 2025Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Cerebral proteome adaptations to amyloid angiopathy are prevented by carbonic anhydrase inhibitors.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Cerebral amyloid angiopathy: a narrative review.Frontiers in aging neuroscience · 2025Review
- Article
- Combination treatment with cilostazol and isosorbide mononitrate attenuates microemboli-mediated vascular cognitive impairment and improves imaging and plasma biomarkers in diabetic rats.Experimental neurology · 2025Article
- Approaches for Increasing Cerebral Efflux of Amyloid-β in Experimental Systems.Journal of Alzheimer's disease : JAD · 2024Review
- Behavioral and Neuronal Characterizations, across Ages, of the TgSwDI Mouse Model of Alzheimer's Disease.Genes · 2023Article
- Levosimendan inhibits disulfide tau oligomerization and ameliorates tau pathology in TauExperimental & molecular medicine · 2023Article
- The lymphatic drainage systems in the brain: a novel target for ischemic stroke?Neural regeneration research · 2023Review
- Emerging Potential of the Phosphodiesterase (PDE) Inhibitor Ibudilast for Neurodegenerative Diseases: An Update on Preclinical and Clinical Evidence.Molecules (Basel, Switzerland) · 2022Review
- Phosphodiesterase (PDE) III inhibitor, Cilostazol, improved memory impairment in aluminum chloride-treated rats: modulation of cAMP/CREB pathway.Inflammopharmacology · 2022Article
- Efficacy and safety of cilostazol in decreasing progression of cerebral white matter hyperintensities-A randomized controlled trial.Alzheimer's & dementia (New York, N. Y.) · 2022Article
- Reversal of spatial memory impairment by phosphodiesterase 3 inhibitor cilostazol is associated with reduced neuroinflammation and increased cerebral glucose uptake in aged male mice.Frontiers in pharmacology · 2022Article
- Cilostazol for Secondary Stroke Prevention: History, Evidence, Limitations, and Possibilities.Stroke · 2021Review
- Current Management and Therapeutic Strategies for Cerebral Amyloid Angiopathy.International journal of molecular sciences · 2021Review
- Conversion from cilostazol to OPC-13015 linked to mitigation of cognitive impairment.Alzheimer's & dementia (New York, N. Y.) · 2021Article
- Novel Targets and Interventions for Cognitive Complications of Diabetes.Frontiers in physiology · 2021Review
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
Abstract
objectiveBrain amyloidosis is a key feature of Alzheimer's disease (AD). It also incorporates cerebrovascular amyloid β (Aβ) in the form of cerebral amyloid angiopathy (CAA) involving neurovascular dysfunction. We have recently shown by retrospective analysis that patients with mild cognitive impairment receiving a vasoactive drug cilostazol, a selective inhibitor of phosphodiesterase (PDE) III, exhibit significantly reduced cognitive decline. Here, we tested whether cilostazol protects against the disruption of the neurovascular unit and facilitates the arterial pulsation-driven perivascular drainage of Aβ in AD/CAA.
methodsWe explored the expression of PDE III in postmortem human brain tissue followed by a series of experiments examining the effects of cilostazol on Aβ metabolism in transgenic mice (Tg-SwDI mice) as a model of cerebrovascular β-amyloidosis, as well as cultured neurons.
resultsWe established that PDE III is abnormally upregulated in cerebral blood vessels of AD and CAA subjects and closely correlates with vascular amyloid burden. Furthermore, we demonstrated that cilostazol treatment maintained cerebral hyperemic and vasodilative responses to hypercapnia and acetylcholine, suppressed degeneration of pericytes and vascular smooth muscle cells, promoted perivascular drainage of soluble fluorescent Aβ1-40, and rescued cognitive deficits in Tg-SwDI mice. Although cilostazol decreased endogenous Aβ production in cultured neurons, C-terminal fragment of amyloid precursor protein expression was not altered in cilostazol-treated Tg-SwDI mice.
interpretationThe predominant action of cilostazol on Aβ metabolism is likely to facilitate Aβ clearance due to the sustained cerebrovascular function in vivo. Our findings mechanistically demonstrate that cilostazol is a promising therapeutic approach for AD and CAA.
Identifiers
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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.