Methods Of the Week

Week 1

Citation:  Matthews, Dawn C., et al. "Physical activity, Mediterranean diet and biomarkers-assessed risk of Alzheimer’s: a multi-modality brain imaging study." Advances in molecular imaging4.4 (2014): 43.

This study looks at the effects that diet and exercise has on the risk of developing Alzheimer's disease through the use of biomarker evidence. Forty-five participants were assessed on their dietary and physical statuses through the use of various questionaires. All subjects also received MRI, PiB, and FDG-PET scans. After analysis of the scans and reports was completed, it was shown that low participation in physical activity and a Mediterranean diet can be associated with a risk of Alzheimer's. 

Week 2 

It has been shown that Alzheimer's disease can be caused by brain perfusion. Pulsed arterial spin labeling is a MRI technique that can assess brain perfusion. Their main goal was to investigate cerebral blood flow abnormalities in the medial temporal and pariental lobes. In this study,  24 healthy adults participants submitted an MRI, while 24 adult participants with Alzheimer's or MCI also submitted an MRI. The pulsed star labeling of arterial regions technique was applied here. They found that patients with Alzheimer's had significant lower perfusion in the posterior cingulate gyrus, middle occipital lobe, and the lateral parental lobe.  These findings were consistent with previous studies utilizing similar techniques. Therefore, PASL imaging might become a good alternative method to discover changes in the brain with people who have Alzheimer's disease. 

Citation: Alexopoulos, Panagiotis, et al. "Perfusion abnormalities in mild cognitive impairment and mild dementia in Alzheimer’s disease measured by pulsed arterial spin labeling MRI." European archives of psychiatry and clinical neuroscience 262 (2012): 69-77.

Week 3

Oxidative stress in neurons has been well-researched in studying Alzheimer's Disease. To study the role of oxidative stress in DNA and RNA relative to Alzheimer's Disease, examinations of 8-OHdG and 8OHG markers were performed to determine whether DNA or RNA oxidation has the biggest impact. To do this, brain tissue was obtained at autopsy of people with AD and compared to senile, presenile, and young controls. After various analytic techniques were performed on the tissue, the researches concluded that their results reinforce the understanding that nucleic acid oxidation increases in people with AD, but also that this increase happens in select neurons. These select neurons have been determined to be involved in cytoplasmic RNA. 

Citation: Nunomura, Akihiko, et al. "RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer’s disease." Journal of Neuroscience 19.6 (1999): 1959-1964.

Week 4

In this study, researchers wanted to determine whether disrupted axonal transport is an important factor in early processes in AD in rats. The study used a manganese-enhanced MRI as a trans-synaptic axonal tracing agent. Disruption was measured by lesioning the lateral olfactory tract. The results yielded a signal changes in axonal projections and decreased axonal transport in rats with AD. They found that disrupted axonal transport can be a major process in AD. 

Citation: Minoshima, Satoshi, and Donna Cross. "In vivo imaging of axonal transport using MRI: aging and Alzheimer’s disease." European journal of nuclear medicine and molecular imaging35 (2008): 89-92.

Week 5

A decrease of acetylcholinergic neurons in the basal forebrain has been hypothesized to contribute to cognitive impairment that occurs with aging. Recently, cholinergic cells in the basal forebrain have been shown to affect certain aspects of attention. This study used 22 three month old male rats and 16 eighteen month old rats. Cholinergic lesions were created by injecting IgG-192 saporin into the basal forebrain. The rats were then placed in an operant box . The attention test required the rats to hit one of two levers in response to light being shown above that specific lever. If correct, the rats received water as a reward. They found that the lesions impaired both young and old rats' accuracy on all stimulus frequencies. They also found a significant effect between age and lesion with respect to discriminability of stimulus. In addition, levels of ChAT in the brain were greatly reduced in rats who were injected with saporin. In this study, they observed that loss of cholinergic imput did not impair performance at all stimulus frequencies, as expected. They suggest that loss of cholinergic cells alone impairs ability to discriminate between stimuli. 

Citation: Stoehr, James D., et al. "The effects of selective cholinergic basal forebrain lesions and aging upon expectancy in the rat." Neurobiology of learning and memory 67.3 (1997): 214-227.

Week 6

This study aims to test whether a7 nicotinic receptors are involved in the pathogenesis of AD. The study utilized transgenic mouse models that express a high amount of APP and lack the a7 nicotinic receptors. Learning and memory tests were performed on the mice, as well as motor coordination and balance tasks. After analysis of neurodegeneration and human levels of APP and Ab, the researchers determined that with the high presence of amyloid deposits, deletion of the a7 nicotinic receptor subtype can lead to protection from disfunction in learning and memory behavior. Deletion of the receptor also protected the brain from the loss of certain synaptic markers. 

Citation: Dziewczapolski, Gustavo, et al. "Deletion of the α7 nicotinic acetylcholine receptor gene improves cognitive deficits and synaptic pathology in a mouse model of Alzheimer's disease." Journal of Neuroscience 29.27 (2009): 8805-8815.