In a recent study published in the Journal of Alzheimer’s Disease, a team of researchers from The University of Texas Medical Branch at Galveston found that that individuals treated daily with calcineurin inhibitors to prevent solid organ transplant rejection have a significantly lower incidence of AD/dementia as compared to the general population.
Alzheimer’s disease (AD) is the most common age-associated neurodegenerative disorder for which there is no resolving cure. Compelling evidence indicates that small soluble oligomers of amyloid-B(AB) protein that precede senile plaque formation are the most toxic AB species in the AD brain known to selectively target synaptic integrity and function. Consequently, there is large consensus that preventing AB oligomer synaptotoxicity would be an effective treatment strategy.
Calcineurin (CN) is an important phosphatase modulating synaptic activity and memory formation. Excess CN activity disrupts synaptic architecture and impairs memory but also its complete suppression negatively affects memory.
In a previous study, the research team found blocking calcineurin restored memory function in AD mouse models. In this new study the researchers aimed to examine if calcineurin could prevent AD’s onset and progression. To do this, they assessed data retrieved from medical records of a total of 2,644 patients who received organ transplants and were under treatment for the rest of their lives with calcineurin inhibitors, such as cyclosporine or Tacrolimus (to prevent rejection of the transplanted organ).
The researchers recorded and monitored any evidence of dementia or memory impairment, as it is a limitation for treatment compliance in this group of patients. Patients were then assigned to one of two groups by age at the time of last visit or death, ethnicity and gender.
Results revealed that 8 patients had signs of dementia, 2 were aged under 65 years, 5 were aged between 65 and 74 years, and 1 was aged between 75 and 84 years..
The UTMB study data was compared with national data obtained from the 2014 Alzheimer’s Association Facts and Figures dataset on age-matched patients to compare the prevalence of Alzheimer’s.
“These data clearly show that the prevalence of dementia and Alzheimer’s in our transplant patient group is significantly lower, in fact almost absent, when compared to national data from the general population,” said in a recent news release senior author Luca Cicalese, professor in the department of surgery. “In patients over 65 years, 11 percent of the general population had dementia compared with 1.02 percent of the study subjects. In Americans over 75 years, 15.3 percent of the population had dementia compared with 0.6 percent of the study subjects. Among Americans over 85 years, 32 percent had dementia, although we did not have any patients in this age group with dementia.”
The study participants were mainly from Texas. For this reason, the research team compared their over 65 years old group with the prevalence of AD in a general population sample from the same state achieving identical results.
“Taken together, our findings from these people confirm the data obtained with animal models and support, for the first time in human subjects, our notion that calcineurin inhibition has a protective effect on the development and possible progression and even reversal of Alzheimer’s disease,” said senior author Giulio Taglialatela, Professor and Vice Chair for Research in the department of neurology and director of UTMB’s Mitchell Center for Neurodegenerative Diseases. “Therefore, we are currently working on devising treatment strategies to obtain the same beneficial effects in AD humans using low doses of calcineurin inhibitors that result in minimal or no immunosuppression, thus limiting possible undesired side effects.”