**Author details**

tumours, renal cell cancer and pancreatic cancer. Sunitinib was shown to decrease the amyloid burden and reverse cognitive decline in AD model mice, suggesting that if we target angio‐ genesis, we can revert the increase in the accumulation of Aβ and abate the cognitive decline

We now know that VEGF is the prime and central component of pathological blood vessel formation. There are biologics and small molecules that specifically target the ligand or its receptor. This specific‐targeted therapy could prove more efficient and less deleterious due to avoidance of unwanted 'off target' effects. A potential therapeutic is Bexarotene, a retinoid X receptor agonist, is shown to facilitate Aβ clearance via activation of apolipoprotein (APOE) expression and promoting microglial phagocytosis [78]. Bexarotene counteracts VEGF‐ mediated angiogenesis by decreasing blood vessel density and reversing cognitive deficits in

These are examples of some of the therapeutic routes that could target angiogenesis; however, understanding the molecular mechanism behind angiogenesis causing eventual AD pathology is of utmost importance in order to look for safe and effective novel therapeutics for AD and

As the Western world ages, AD represents an ailment that will place a significant burden on all the aspects of society. This burden, primarily placed on family caregivers, has been estimated to cost billions in lost productivity and healthcare costs (both direct and indirect). Currently, there is a lack of understanding regarding the cause(s) of the disease that translates into a lack of viable treatments or cures. Over the years, limited progress has been made with regards to the clinical translation of the popular amyloid hypothesis for treating AD and hence new thinking towards AD pathogenesis is required. Vascular risk factors and neurovascular dysfunction associated with hypotension, hypertension, cholesterol levels, type II diabetes mellitus, smoking, oxidative stress and iron overload have been found to play integral roles in the pathogenesis of stroke and AD. Observations showing increased cerebrovascular permeability prior to the appearance of the hallmarks of AD, sprout a novel paradigm for integrating vascular remodelling (angiogenesis) with the pathophysiology of the disease. Taking this into account, research focused on understanding the molecular mechanism behind the pathophysiology of angiogenesis leading to AD pathology will mediate in developing novel therapeutic interventions targeting this pathological blood vessel formation help to

associated with AD [76].

AD mice [78].

other vascular diseases.

**5. Concluding remarks**

alleviate the global societal burden of AD.

**4.2. Biologics and small molecule VEGFR inhibitors**

102 Physiologic and Pathologic Angiogenesis - Signaling Mechanisms and Targeted Therapy

Chaahat Singh1,3, Cheryl G. Pfeifer1 and Wilfred A. Jefferies1,2,3,4,5,6\*

\*Address all correspondence to: wilf@msl.ubc.ca

1 The Michael Smith Laboratories, University of British Columbia, Vancouver, Canada

2 Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada

3 Department of Medical Genetics, University of British Columbia, Vancouver, Canada

4 Department of Zoology, University of British Columbia, Vancouver, Canada

5 Centre for Blood Research, University of British Columbia, Vancouver, Canada

6 Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada

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**Angiogenesis in the Cardiovascular System**

**Provisional chapter**
