Fibrin deposition accelerates neurovascular damage and neuroinflammation in mouse models of Alzheimer's disease.
Level 5 - mechanism / opinion, no new human data
Animal model study without human participants
PubMed 17664291 · doi:10.1084/jem.20070304
What was done
Using transgenic mouse models of Alzheimer's disease (TgCRND8, PDAPP, and Tg2576), the authors evaluated blood-brain barrier permeability via Evans blue extravasation and assessed the role of fibrin and fibrinolysis. They tested genetic alterations (AD mice with single functional plasminogen or fibrinogen genes) and pharmacological interventions (plasmin inhibition via tranexamic acid, fibrinogen depletion via ancrod, and ancrod pretreatment before plasmin inhibition) on vascular pathology and neuroinflammation.
What was found
The abstract reports no numerical values, confidence intervals, or p-values. It reports that AD mice exhibited age-dependent fibrin deposition coincident with blood-brain barrier permeability. AD mice with one functional plasminogen gene had increased neurovascular damage, whereas AD mice with one functional fibrinogen gene had decreased blood-brain barrier damage. Tranexamic acid aggravated pathology, ancrod attenuated neuroinflammation and vascular pathology, and ancrod pretreatment reduced the pathology induced by plasmin inhibition.
Why it matters
This study links cerebrovascular fibrin deposition to accelerated blood-brain barrier breakdown and neuroinflammation in Alzheimer's models, highlighting fibrin clearance mechanisms as potential therapeutic targets.
Limits
The study is entirely preclinical in transgenic mouse models, limiting direct translation to human Alzheimer's disease. The abstract reports no sample sizes (n is unknown), quantitative effect sizes, or statistical certainty measures.
Cited by
- supports Fibrinogen extravasates and deposits in brain parenchyma in Alzheimer's disease and small vessel disease due to blood-brain barrier breakdown.