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Gamechanging human study identifies 3 distinct subtypes of Alzheimer’s disease.

The need for a new approach to treat Alzheimer’s is an urgent priority for governments across the globe.  It is the most common age-related dementia, and the number of people with the disease in the U.S. is expected to increase to 15 million in 2050, from nearly 6 million today. The cost to treat people in the U.S. with Alzheimer’s and other dementias is expected to be $226 billion in 2015 alone, and could reach $1.1 trillion in 2050.  Recent estimates suggest that AD has become the third leading cause of death in the United States, behind cardiovascular disease and cancer.  Unlike several other chronic illnesses, Alzheimer’s disease prevalence is on the rise, which makes the need to develop effective prevention and treatment increasingly pressing.

Now, a study from researchers at UCLA has shown that Alzheimer’s disease, long thought to be a single disease, really consists of three distinct subtypes.  The team state that the finding could lead to more highly targeted research and, eventually, new treatments for the debilitating neurological disorder, which robs people of their memories.  The opensource study is published in the journal Aging.

In an earlier study from the team, results showed that making lifestyle, exercise and diet changes designed to improve the body’s metabolism reversed cognitive decline in nine out of 10 patients with early Alzheimer’s disease or its precursors.  The lab state that the current study grew out of an extensive evaluation of the data from last year’s study, and that it could eventually help researchers pinpoint more precise targets for treatments, the same approach that has led to major advances in treating other diseases.  As the presentation varies from person to person, there has been suspicion for years that Alzheimer’s represents more than one illness.  However, in Alzheimer’s disease, there is no tumor to biopsy, so the group faced the challenge of understanding what is driving the process.  The approach they took was to use the underlying metabolic mechanisms of the disease process to guide the establishment of an extensive set of laboratory tests, such as fasting insulin, copper-to-zinc ratio and dozens of others.

The current study involved the metabolic testing of 50 people with cognitive decline over two-years.  The metabolic profiling of patients with cognitive decline reveals three readily distinguishable subtypes of Alzheimer’s disease, inflammatory, non-inflammatory, and cortical. Results show that the distinctive features, presentation, lack of association with ApoE4, and marked hypozincemia, suggest that the cortical subtype of Alzheimer’s disease is a fundamentally different disease than the other two subtypes. The team note that this subtype deserves further genetic, epigenetic, and metabolomic studies.

Data findings show that clinical metabolic testing reveals three readily distinguishable subtypes of Alzheimer’s disease.  The subtypes are, inflammatory, in which markers such as C-reactive protein and serum albumin to globulin ratios are increased; non-inflammatory, in which these markers are not increased and other metabolic abnormalities are present; and the cortical subtype, which affects relatively young individuals and appears more widely distributed across the brain than the other subtypes of Alzheimer’s.

The group state that the cortical subtype typically does not seem to cause memory loss at first, however, people with this subtype of the disease tend to lose language skills. They go on to add that the cortical subtype is often misdiagnosed, typically affects people who do not have an Alzheimer’s-related gene and is associated with a significant zinc deficiency.

The team surmise that their study shows that when laboratory tests go beyond the usual tests, these three distinct subtypes are identified.  They go on to add that the important implications of this are that the optimal treatment may be different for each group, there may be different causes, and, for future clinical trials, it may be helpful to study specific groups separately.  For the future, the researchers will seek to determine whether the subtypes have different underlying causes, and whether they respond differently to potential treatments.

Source:  University of California – Los Angeles Health Sciences

Alzheimer's disease consists of 3 distinct subtypes, according to UCLA study - neuroinnovations


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