Sugary Protein Could Play Key Role In Alzheimer’s Disease

In a bit of “reverse engineering” research using brain tissues from five people who died with Alzheimer’s disease, Johns Hopkins Medicine researchers say they discovered that a special sugar molecule could play a key role in the development of Alzheimer’s disease. If further research confirms the finding, the molecule, known as a glycan, could serve as a new target for early diagnostic tests, treatments and perhaps prevention of Alzheimer’s disease, say the researchers.

Alzheimer’s disease is the most common form of dementia in the United States. Affecting an estimated 5.8 million Americans, the progressive disorder occurs when nerve cells in the brain die due to the buildup of harmful forms of proteins called amyloid and tau.

Cleaning up the disease-causing forms of amyloid and tau is the job of the brain’s immune cells, called microglia. Earlier studies found that when cleanup is impaired, Alzheimer’s disease is more likely to occur. In some people, this is caused by an overabundance of a receptor on the microglia cells, called CD33.

A sugar molecule, known as a glycan, could serve as a new target for early diagnostic tests, treatments, and perhaps prevention of Alzheimer’s disease

Receptors are not active on their own. Something needs to connect with them to block microglia from cleaning up these toxic proteins in the brain,” says Ronald Schnaar, Ph.D., the John Jacob Abel Professor of Pharmacology at the Johns Hopkins University School of Medicine and director of the laboratory that led the study.

Past studies by the researchers showed that for CD33, these “connector” molecules are special sugars. Known to scientists as glycans, these molecules are ferried around the cell by specialized proteins that help them find their appropriate receptors. The protein-glycan combination is called a glycoprotein.

The study was published online April 20 in the Journal of Biological Chemistry.


NK cells give our immune system long-term memory

I’ll be honest, when I first started working on this I didn’t fully accept it.”
That’s Dr. Andrew Makrigiannis, head of the Department of Microbiology & Immunology at the Dalhousie University., discussing his groundbreaking research on natural killer cells that was published in the leading journal Proceedings of the National Academy of Sciences.“I’m a traditionally trained immunologist; I was skeptical”.
NK cells were originally discovered due to their novel ability to recognize and kill tumour cells without having previously encountered these aberrant cells, unlike other lymphocytes such as T and B cells.

One of the receptor families on NK cells which have been shown to play an important role in tumour recognition are the Ly49 receptor family.
Class I major histocompatibility complex (MHC-I) molecules are expressed on all nucleated cells and function as a marker of a “healthy” cell for NK cells. Ly49 receptor family recognition and binding to the host’s MHC-I molecule will signal to the NK cell not to kill this cell since it is healthy.


Alternatively, in transformed cells, such as those which are virally-infected or cancerous, MHC-I expression is reduced on the cell surface, and so, the NK cell now recognizes this cell as being an unhealthy cell. These cells are killed by the NK cell through various means such as direct cytotoxicity or indirectly through cytokine secretion and recruitment of other.

We observed that NK cells from mice with knocked-down expression of the Ly49 receptor family have defective killing of traditional tumour target cells which lack MHC-I expression in both in vitro [51Cr]-release cytotoxicity assays and in vivo rejection assays. Using different carcinoma models such as oncogene-driven lymphoma and carcinogen-induced sarcoma, we observed that mice with knocked-down expression of the Ly49 receptor family show defective tumour control. Specifically they are prone to earlier cancer development as well as metastatic formation. As well, through the use of antibodies and flow cytometry analysis of tumours isolated from Ly49-knock-down and wildtype mice, it was seen that there is differential expression of MHC-I. This observation suggests that tumours which grow in the knock-down mice are phenotypically different from those in the WT mice due to their altered immune environments which directly affect how these tumours develop.