Cause of Alzheimer’s May Also Be the Cure

Scientists from the Carol Besta National Neurological Institute have found that a newly discovered gene mutation, thought to be the cause of Alzheimer’s disease when inherited from both parents, may give protection from the disease when only one copy is inherited. Mutations in the Amyloid beta (A4) precursor protein (APP), which is responsible for providing instructions for making the amyloid precursor protein, a protein located in many tissues and organs including the brain and stem cell and thought to be important in the binding of cells and proteins, have long been considered a possible cause of Alzheimer’s disease. Mutations in the amyloid precursor protein cause the protein to stick together and block neurons from communicating with one another. These “clumps” have been found to underlie the some of the symptoms of Alzheimer’s such as memory and speech difficulties. Scientists now however have discovered the presence of a single inherited mutation of APP may in fact prevent the onset of the disease.

Fabrizio Tagliavini, a neurologist at the Carol Besta Institute, and his team uncovered the mutation in a person who showed signs of early-onset Alzheimer’s but who lacked mutations in other genes associated with the inherited form of the disease. The 44-year-old man with two copies of the mutated APP gene first showed signs of Alzheimer’s in his mid-thirties and his younger sister, also with two copies of the mutated APP gene also showed signs of cognitive problems, however his relatives with a single copy of the mutation seem to be protected from the disease. When normal and mutant forms of the protein were mixed, the team found the mixture clumped far less often than the mutant protein or normal protein alone. This could explain why the patient’s relatives with a single mutation showed no signs of the disease.

Using this new information Tagliavini and his team have already found that a mutant protein, only six units long, is enough to keep the proteins from forming clumps. Tagliavini admits the potential therapy will need much more work and testing, however this kind of smaller protein has a better chance of travelling from blood vessels across the blood-brain barrier and into the brain then previously seen therapies. Whatever happens, this newly discovered APP mutation will change how researchers thing about the genetics of the disease as the first recessive mutation seen in Alzheimer’s disease to date.

Reference List:
Callaway, J 2009, “Paradoxical gene causes and protects against Alzheimer’s” New Scientist http://www.newscientist.com/article/dn16750-paradoxical-gene-causes-and-protects-against-alzheimers.html
Genetics Home Reference, Amyloid Beta (A4) Precursor Protein: http://ghr.nlm.nih.gov/gene=app
Alzheimer Solutions, Genetic Factors http://alzheimersolutions.stores.yahoo.net/geneticfactors.html
Adams, A 2008, “Genes Can Cause Alzheimer’s Disease” Genetic Health http://www.genetichealth.com/alz_genetics_of_alzheimers_disease.shtml

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