The Role of Sulfatide in Alzheimer's Disease

Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta plaques, neurofibrillary tangles (NFT) and loss of cortical neurons that control memory and cognition. The cause of NFTs and Aβ plaques is not clear, though it is known that they are formed by enzymes which are preferentially sequestered to membrane domains called lipid rafts. Sulfatide (ST) is a glycosphingolipid that is essential for the proper structure and function of lipid rafts. In mice that lack ST, membrane domains that are normally maintained by adhesive contacts and functional lipid rafts are improperly formed and are unstable. In these ST null mice, voltage gated sodium channels, neuronal proteins that normally cluster at the nodes of Ranvier, initially accumulate in the node but are not retained with age. Taken together the findings from the ST null mice indicate that membrane organization is compromised. Recently, a published report demonstrated that ST is significantly reduced in AD. Based on this observation combined with the findings from the ST null mice, I propose that membrane architecture is also altered in AD and this alteration may facilitate AD pathogenesis. To test this hypothesis, I have used an immunohistochemical approach to assess neuronal membrane organization in AD and non-AD brain samples. Analysis of the sodium channel clusters was chosen since these nodal domains provide an easy assessment tool for membrane organization. In the current study, sodium channel domains were not altered and no change in isoform expression was observed. Based on these findings, membrane organization does not appear to be altered in AD. It is important to note, however, that sodium channel clusters are restricted to a specific region of the axon and thus membrane organization within other regions of the axon and in other regions of the neuron may be altered. Additionally, assessment of the brain samples, using thin layer chromatography, did not show a reduction in ST levels between the AD and non-AD brains. Therefore, my study strongly suggests that further analysis of ST levels in AD brains should be conducted to resolve the contrasting results between the current study and the previously published work.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Anatomy & Neurobiology

Year dc:date.available

2006

Author dc:creator

• Beasley, Charles Britton, Jr.

Contributors dc:contributor

• Dr. Jeffrey Dupree

• glycosphingolipid
• enzyme
• dementia
• Anatomy
• Medicine and Health Sciences
• Nervous System

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/1053

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-2052