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Metabolic Profiling Distinguishes Three Subtypes of Alzheimer’s Disease

Metabolic Profiling Distinguishes Three Subtypes of Alzheimer’s Disease

Alzheimer's disease is a complex, irreversible brain disorder that slowly destroys memory, thinking skills, and the ability to carry out simple tasks as the disease and time progresses. And while it was once thought to be a single disease, growing evidence suggests there are three different subtypes of Alzheimer's, which may be highly beneficial in providing an effective treatment option for those affected.

The Three Subtypes of Alzheimer's Disease

Though advancing age, genetics, obesity, depression, physical inactivity and several other risk factors heighten the risk of Alzheimer's disease (AD), the cause of AD remains convoluted and multifactorial. Opportunely, though, multiple reports have pointed to metabolic abnormalities and hormonal deficiencies as underlying causes for Alzheimer's development. In fact, a recent UCLA study published in Aging discovered three subtypes of Alzheimer's disease with metabolic profiling, or "the measurement in unicellular to multicellular biological systems of the complement of low-molecular-weight metabolites and their intermediates that reflects the dynamic response to genetic modification (e.g., transgenic or viral) as well as physiological (e.g., gender), pathophysiological (e.g., disease morbidity), and/or developmental stimuli (e.g., aging). The study's author, Dr. Dale Bredesen, went on to say in a UCLA Newsroom statement, "Because the presentation varies from person to person, there has been suspicion for years that Alzheimer's represents more than one illness" and "When laboratory tests go beyond the usual tests, we find these three distinct subtypes:"

Type 1: Inflammatory
Type 1 Alzheimer's disease is characterized by systemic inflammation. Elevated inflammatory biomarkers are present, including C-reactive protein (CRP) and serum albumin to globulin (A/G) ratios; CRP is a biomarker of inflammation found in the blood, while an elevated A/G ratio is indicative of a generalized disease state. High cytokine levels, such as interleukin-1 and interleukin-6, may also be present in type 1 AD.

Type 2: Non-Inflammatory
In non-inflammatory Alzheimer's disease, inflammatory biomarkers are not increased, but rather presents with metabolic abnormalities. Type 2 is characterized by an atrophic profile, meaning the body's cells, organs, or tissues are wasting or decreasing in size. So in the case of type 2 AD, atrophy causes reduced support from molecules such as estradiol, progesterone, testosterone, and vitamin D, which is often accompanied by increased homocysteine levels and insulin resistance.

Type 3: Cortical
Type 3 cortical AD typically affects people who do not have an Alzheimer's-related gene and is associated to a significant zinc deficiency. It also affects younger individuals and appears more widely distributed across the brain than the other subtypes of Alzheimer's. Type 3 is also dissimilar to the other two; it typically does not seem to cause memory loss in the initial presentation, but rather affected individuals tend to lose the long-term memory maintenance and language skills. Type 3 has also been documented and explored as Inhalation Alzheimer's disease (IAD) with evidence linking mold, brain inflammation, and cognitive decline.

Implications of Discovering Types of Alzheimer's Disease

The need for effective Alzheimer's treatment is urgent, as AD is the third leading cause of death in the United States. Most current statistics estimate over five million Americans suffer from Alzheimer's, and the number is only expected to grow to 15 million in 2050. The projected AD growth surges healthcare costs to potentially reach $1.1 trillion in 2050! And while there is no effective standard to cure or treat AD, researchers are gearing towards a more programmatic approach. In fact, Dr. Bredesen coined and implemented a protocol that encourages making healthy lifestyle changes to improve the body's metabolism.

Ultimately, identifying and distinguishing subtypes offers an opportunity to manage the condition based on its own targeted criteria, potentially in hopes to mitigate the severity of Alzheimer's disease. "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," states Dr. Bredesen. Nonetheless, one of the most effective strategies to optimize treatment development is to identify specific subtypes of Alzheimer's disease that may respond to different optimal programs.