A disease often described as a modern-day epidemic in an aging society, robbing us of our autonomy, our memories, and ultimately our lives.
The IRCM is at the heart of the fight against Alzheimer and associated diseases. Dr. Hideto Takahashi’s lab is making powerful strides toward a deep understanding of these diseases. He kindly answered our questions on Alzheimer.
What is Alzheimer, quickly summed up?
Alzheimer’s disease (AD) is a major neurodegenerative disease and the most common types of dementia. The symptoms of AD are not only memory impairment, but also problems on familiar tasks, communication and abstract thinking, and also associated with changes in mood, personality, and so on. Due to the aging of many developed countries including Canada, AD is a very serious disease burden to diminish quality of life in our society.
Who is affected
In general, AD affects people aged 60 years old or older, suggesting that age is a major risk factor for AD. Elder women may have more prevalence in AD than elder men. Most cases are sporadic without specific familial linkage.
Why does research fail to this day to find ways to cure the disease?
AD brains show two major pathological hallmarks, one is the deposit of senile plaques, which is the accumulation of brain debris called amyloid-beta (Ab) peptides, and the other is the accumulation of neurofibrillary tangles. Many previous studies have proposed and supported ‘amyloid hypothesis’ that the accumulation of Ab peptides is a primary cause of AD pathology. Based on this hypothesis, many drugs have been developed to target Ab peptides and the process of Ab production. As you know, none of clinical trials using these drugs show expected effective therapeutic outcome. These unfortunate results may tell us that other molecular targets should be addressed.
Which avenues of research does your lab tackle in relation with this disease?
My lab tried to understand how brain cell communications are damaged in AD and how these damages are prevented and/or cured by identifying novel molecular mechanisms that control brain cell communications. We have recently uncovered that a key molecule that controls brain cell communication called neurexin directly interacts with Ab peptides, and their interaction is linked with the damage of brain cell communications. Further, we have identified another gene called SorCS1 as a protector of neurexin from Ab peptides that inhibits Ab-induced pathology. Given our positive results in cell culture studies, as a next step, we currently investigate whether and how SorCS1 can rescue memory impairment in AD model mice by developing a unique genetic strategy.
