23 July 2015

Alzheimer's disease: early diagnosis

American researchers working under the leadership of Dr. Andrew J. Saykin from Indiana University have found that the most well-known of the genetic variants associated with Alzheimer's disease can have its detrimental effect, contributing to the formation of protein deposits in brain tissue, long before the first symptoms of the disease can be detected with the help of existing methods.

As the object of the study, people with serious memory problems were selected, who were identified by the authors as elderly people complaining of memory lapses over the past few months or years, but receiving normal results when passing standard tests for the state of cognitive functions and memory. Experts on Alzheimer's disease describe this condition as a "subjective extinction of cognitive functions."

In carrying out the work, the authors used data on almost 600 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI), a global public–private project that collects a wide range of data related to Alzheimer's disease and provides access to this data. The collected data include images of the brain obtained using magnetic resonance and positron emission tomography, biomarkers of glucose metabolism, data on the content of beta-amyloid and tau protein in cerebrospinal fluid, genetic data, as well as the results of clinical examinations and testing of cognitive functions of volunteers whose condition varies from normal (control group) before clinically confirmed Alzheimer's disease.

The gene encoding the protein apolipoprotein E studied by the authors has several variants – alleles. One of these variants, APOE e4, is associated with an increased risk of developing Alzheimer's disease. However, not all patients with the disease are carriers of this allele, and not all of its carriers develop Alzheimer's disease. APOE e4 is quite widespread, its frequency of occurrence is approximately 25%. In patients with this allele, symptoms of Alzheimer's disease usually appear at an earlier age.

When comparing data on carriers of the APOE e4 allele and people without it, researchers found that elderly people with severe memory impairments who are carriers of the APOE e4 allele are characterized by manifestations of Alzheimer's-like pathologies, including:
  • an increase in the number of amyloid plaques – aggregates consisting of protein fragments and usually detected in the brain tissue of patients with Alzheimer's disease;a decrease in the concentration of the precursor protein of amyloid plaques in the cerebrospinal fluid, which indicates the movement of this protein into the brain tissue, where the active formation of plaques occurs;
  • an increase in the content of tau protein in the cerebrospinal fluid - another protein associated with Alzheimer's disease.
  • Various regions of the brain of elderly people with "subjective extinction of cognitive functions" who are carriers of the APOE e4 allele (bottom) show a greater amount of protein deposits compared to the brain of elderly people who do not have this allele (top).

Image: Indiana University School of Medicine.

However, the analysis did not reveal signs of a decrease in the activity of glucose metabolism and degeneration of brain structures characteristic of the late stages of Alzheimer's disease.

The authors claim that as the need for interventions aimed at combating Alzheimer's disease becomes more and more obvious long before the onset of symptoms of the disease, specialists are beginning to work more closely with people at risk who have serious memory disorders. The data obtained also indicate the exceptional importance of further work with such patients. The researchers also note that in addition to pharmacological therapy, there are many potentially effective approaches, such as exercise, diet optimization, cognitive stimulation, normalization of sleep patterns and other lifestyle factors. The influence of many of these factors on the progress of Alzheimer's disease is currently being actively studied.

Article by Shannon L. Risacher et al. APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern is published in the journal Alzheimer's and Dementia.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on EurekAlert materials!:
Impact of major Alzheimer's-related gene may be felt years before any symptoms appear.  

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