Feb 15, 2012Science and Technology
Many exciting developments in the fight against Alzheimer’s disease

Alzheimer’s disease has had a strong presence in the news lately, between the Obama administration announcing a funding boost, the National Institute on Aging and the Alzheimer’s Association releasing new guidelines for classifying Alzheimer’s disease, and a known cancer treatment drug demonstrating efficacy in reversing Alzheimer’s symptoms in mice. Alzheimer’s is clearly in the forefront of our minds, so to speak.

As well it should be. Alzheimer’s disease affects five million Americans, and as the baby boomer generation begins to develop symptoms of dementia and cognitive impairment, the need for a better understanding of the disease, and more importantly, a cure, has become increasingly more urgent.

Diagnosing a patient with Alzheimer’s disease at any stage is difficult. In the absence of a standardized blood or brain-imaging test, doctors have had to rely on oral examinations during patients’ visits, which are subjective and imprecise at best. The criteria established in 1997 for diagnosing Alzheimer’s disease (AD) required a history of dementia, the goal being to address the question of whether the AD was the underlying cause of the patient’s dementia.

Yet, as scientists begin to better understand the underlying causes of AD, they are proposing the possibility of a preclinical phase of the illness. The preclinical phase is identified, not by observable symptoms, but rather by the patient’s neuropathology. That is, before the patient has begun to exhibit cognitive impairment or memory loss, she may have developed amyloid beta proteins and amyloid plaques that are the underlying cause of AD.

The new clinical classification addresses this development by emphasizing that Alzheimer’s disease covers a spectrum of symptoms, from none, to mild cognitive impairment, to advanced dementia. Thus, patients registering pathophysiological processes of AD may be identified as having mild cognitive impairment, even in the absence of subjective or objective behavioral deficits.

With this more comprehensive understanding of the disease and its underlying causes, scientists are able to develop new drugs to treat and reverse Alzheimer’s. In one recent case, researchers at Case Western Reserve University discovered that a pharmaceutical that has been in use for cancer treatment for over ten years, bexarotene, also has exciting applications in reversing pathological, cognitive and memory deficits caused by Alzheimer’s in mice.

Bexarotene stimulates retinoid X receptors, which control production of Apolipoprotein (ApoE) expression. ApoE facilitates the clearance of amyloid beta proteins from the brain, the build-up of which, both as plaques and as tangles, is the underlying cause of Alzheimer’s disease. In laboratory studies on mice, soluble amyloid levels fell by seventy-five percent within six hours of treatment, with the results lasting for up to three days. This novel use for this established drug has only been tested on mice thus far, but the possibilities for human applications are exciting.

Of course, further testing of the bexarotene drug and other possible Alzheimer’s treatments require substantial funding. Thankfully, Obama’s administration announced at the beginning of February that it plans to dramatically increase funding for AD research. The proposal includes an additional $80 million in research funding next year, with a further $26 million in funding to help support families and caregivers for Americans suffering from Alzheimer’s disease. Hopefully this additional support will provide the impetus for further developments in the fight against mental decline due to Alzheimer’s. 

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