Sara Ahmed

Introduction Alzheimer’s disease (AD) is the most prevalent cause of dementia and is defined by the presence of β-amyloid peptide and neurofibrillary tangles made of hyperphosphorylated tau proteins in cortical and limbic areas. ^1,2 Overall, the main symptoms of Alzheimer’s disease include a progressive loss of episodic memory and cognitive function decline. ³ Although pharmacotherapy such as cholinesterase inhibitors can help for AD symptoms, there are no curative treatment options currently available. ⁴ Lifestyle modifications such as a Mediterranean diet and regular aerobic exercise could potentially serve as disease modifying treatments.⁵ Studies have shown aerobic exercise has the capability to improve VO2 peak which in turn improves attention and cognition. ⁶ It has also been proven that regular exercise can induce adult hippocampal neurogenesis (AHN) and increase levels of brain derived neurotrophic factor (BDNF) to provide cognitive benefit to 5xFAD mice, a mouse model of AD. ⁷  Methods AHN was stimulated starting at 2 months of age for 4 to 4.5 months by injecting P7C3 and lentivirus expressing Wnt3 (LV-Wnt3) in sedentary 5xFAD mice. These compounds function to enhance neuronal progenitor cell (NPC) survival. Then following the AHN stimulation the effects of exercise were tested on these mice and the results were measured and determined by immunostaining for doublecortin (DCX)+ neurons. Throughout the study the mice participated in a series of cognition tests including retention memory tests and spatial working memory tests such as the RAM and Y-maze.⁷   Results It was seen on day 8 of the study AHN stimulated 5xFAD mice failed to show improvement in the retention memory task while the exercised 5xFAD mice did improve. Overall, it was found that increasing AHN alone did not improve cognitive function, but AHN stimulation and exercise together showed beneficial effects. Exercise improved cognition, reduced Aβ load and increased levels of hippocampal BDNF, IL-6 and fibronectin type III domain-containing protein-5. Additionally, exercise had the capability to increase synaptic proteins such as PSD95 synaptophysin (SYP). ⁷  Conclusion These findings are significant because the data indicates that the promotion of ANG can improve cognition only when the brain is further stimulated by exercise. These findings are potentially very useful, if applied in the early stages of AD exercise and stimulated AHN could improve cognition. Another potential use of increasing neurogenesis early includes protection against neuronal cell death seen later on during the progression of AD.

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