Contribution of the vasculature to the Alzheimer's disease process

One of the pathological hallmarks of Alzheimer's disease (AD) brain is extracellular β-amyloid (Aβ) plaques containing 39-42 amino acid Aβ peptides. The deposition of Aβ around blood vessels, known as Cerebral amyloid angiopathy (CAA), is also a common feature in AD brain. Vascular density and cerebral blood flow are reduced in AD brains, and vascular risk factors such as hypertension and diabetes are also risk factors for AD. We have shown previously that Aβ peptides can potently inhibit angiogenesis both in-vitro and in-vivo, but the mechanism of action for this effect is not known. Therefore, my first hypothesis was that particular amino acid sequence(s) within the Aβ peptide are required for inhibition of angiogenesis. From this aim, I found a peptide sequence which was critical for anti-angiogenic activity (HHQKLVFF). This sequence contains a heparan sulfate proteoglycan growth factor binding domain implying that Aβ can interfere with growth factor signaling. Leading on from this, my second hypothesis was that Aβ can inhibit angiogenesis by binding to growth factor receptors. I found that Aβ can bind to Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2), and showed that this is one mechanism by which Aβ can inhibit angiogenesis. Since the vasculature is disrupted in AD brains, I investigated whether a strategy to increase brain vascularization would be beneficial against AD pathology. Therefore, my third hypothesis was that voluntary exercise (which is known to increase brain vascularization in rodents) can ameliorate Aβ pathology, increase brain vascularization, and improve behavioral deficits in a transgenic mouse model of AD. I found that exercise has no effect on Aβ pathology, brain vascularization or behavioral deficits. Therefore, in the transgenic mouse model that I used, exercise is an ineffective therapeutic strategy against AD pathology and symptoms.

Prolonged Rehabilitation of Jones Fracture in Division I-A Collegiate American Football Player: A Case Report

Objective: To describe the prolonged rehabilitation program for a Jones fracture in a Division I-A American football player. Background: A 21 year old, African American, collegiate football player (body mass= 264 lb; height= 76.5 in; body fat= 16.0%) complained of a sharp pain at the dorsal aspect of the left foot. The athlete experiences a compressive force to the fifth metatarsal and upon evaluation, mild swelling was present along the lateral aspect of the foot. Differential Diagnosis: Jones fracture, metatarsal fracture, bone contusion. Treatment: An intramedullary fixation surgery was scheduled two weeks post injury, to correct and stabilize the fracture. Intramedullary fixation is a method of mending the bone internally with a screw, wire, or metal plate along the fractured bone length wise. Following surgery the athlete continued use of crutches for ambulation and was placed in a removable walking boot for 5 weeks. Uniqueness: This case presented a unique challenge in the rehabilitation program, as the athlete experienced slow formation of the bone callus and therefore a prolonged rate of recovery. The athlete was in a walking boot longer than expected (2 weeks longer than anticipated) which inhibited advancement in his rehabilitation due to a slow bone callus formation. A soft callus usually begins to form at day 5 following injury, but documentation was incomplete, and a hypothesis for slow bone callus formation could be secondary to lengthened time between injury occurrence and injury reporting. The athlete may have been weight bearing during the early callus formation, but healing may have been prohibited. Also, vascularization in the area is already limited and may also have played a role in delayed bone growth. Conclusions: Although the return to participation was longer than expected, the rehabilitation program was successful in returning the athlete to competition.