Alzheimer’s disease can now be detected many years before the presence of symptoms
Scientists at Washington University Alzheimer Disease Research Center have confirmed the existence of a preclinical manifestation of Alzheimer’s disease in older people (65 to 85 years old) who show normal cognitive function but may develop symptoms of Alzheimer’s disease within 20-15 years after the initial diagnosis. Moreover, the study, which included over 135 patients, showed that a reduction in volume of different brain regions is correlated with an abnormal accumulation of protein aggregates.
What is Alzheimer’s disease?
In brief, Alzheimer’s disease is an age dependent, relentless, chronic and incurable neurodegenerative disease characterized by a progressive loss of neurons of the hippocampus and the cortex leading to a progressive decline in cognitive function. The pathological hallmarks of AD is characterized by the presence of protein aggregates located in the axons, dendrites and in cell bodies of neurons. These protein aggregates have been termed neurofibrillary tangles, protein aggregates mainly composed of hyper-phosphorylated tau, and senile plaques, protein aggregates mainly composed of beta-amyloid. The accumulation of these protein aggregates have been associated with neuronal loss as shown by tissue culture studies in multiple neuronal cell lines and in mouse models of Alzheimer’s disease.
How is Alzheimer’s disease detected?
Normally, post-mortem (after death) brain tissue is collected and processed for immunohistochemistry to detect the presence of amyloid beta plaques and tangles in order to confirm cases of Alzheimer’s disease in patients that scored low on cognitive tests. However, nowadays scientists have been able to use a non-invasive methods to detect the presence of amyloid beta plaques in real-time by using a dye that is specific for beta amyloid called “Pittsburgh Compund B” or Pitt-B, which precludes the need to use post-mortem brain tissue in order to confirm an Alzheimer’s case.
As the name implies, this compound was invented and patented at the University of Pittsburgh. The project that led to the creation of this compound was led by geriatric psychiatrist William E. Klunk and radiochemist Chester A. Mathis. The investigators identified Pittsburgh B compound as a type of a benzothiazole, a derivative from thioflavin T, that works well as a positron emission tomography imaging agent. More importantly, Pitt-B has a high affinity for beta amyloid plaques but not for tau or other aggregates. A radiolabeled version of Pitt-B is currently being used worldwide by many hospitals and clinics to monitor and quantify the presence of plaques in real time by MRI in patients.
Synopsis of the University of Washington study
The University of Washington study analyzed a total of 135 individuals aged
65 to 88 years that showed a Clinical Dementia Rating of 0 (or normal test). MRI studies using the Pitt-B compound showed that 23 participants progressed to a clinically detectable dementia from which only nine were confirmed to have Alzheimer’s diseases.
Alzheimer’s disease and normal aging can cause a shrinkage in the total volume of certain brain regions which may be due to neuronal loss. Interestingly, the group of people that showed high levels of Pitt-B reactivity were correlated with modest reductions in the volume of different brain regions which included the hippocampus, temporal neocortex and cingulate gyrus suggesting that shrinkage of these brain regions precedes the development of Alzheimer’s disease symptoms.
Finally, there was an interesting negative correlation in the mean cortical binding potential (staining intensity by Pitt-B) in the Pitt-B positive group with cognitive performance, specifically episodic and working memory but not verbal memory were affected. In other words, the presence of beta amyloid plaques in preclinical Alzheimer’s precedes a decline in memory and the onset of dementia.
Final thoughts- the implications and ramifications of this study and other studies are unknown but it is clear that medical doctors and clinical specialists may use the Pitt-B compound to screen for Alzheimer’s disease in an older patient population or other high risk patient populations, such as those harboring the ApoE allele. Thus in a manner analogous to screening for prostate and breast cancer, this study also suggest that the Pitt-B compound can be used to detect preclinical Alzheimer’s at a extremely early stage.
Does this mean that doctors may have the option of treating preclinical Alzheimer’s disease patients with anti-oxidants and subject them to Mediterranean diets and exercise regimens in order to delay the onset and progression of the disease? You be the judge.
SOURCE: Pittsburgh Medical Technology Examiner
