Navigation Links
Rethinking Alzheimer's disease and its treatment targets

The standard explanation for what causes Alzheimer's is known as the amyloid hypothesis, which posits that the disease results from of an accumulation of the peptide amyloid beta, the toxic protein fragments that deposit in the brain and become the sticky plaques that have defined Alzheimer's for more than 100 years.

Billions of dollars are spent yearly targeting this toxic peptide but what if this is the wrong target? What if the disease begins much earlier, fueled by a natural process? Reporting in the current edition of the journal Neurobiology of Aging, UCLA professor of psychiatry George Bartzokis argues just that and says that a better working hypothesis is the "myelin model."

"The greatest promise of the myelin model of the human brain is its application to the development of new therapeutic approaches," Bartzokis said.

Like insulation around wires, myelin is a fatty sheath that coats our nerve axons, allowing for efficient conduction of nerve impulses. It is key to the fast processing speeds that underlie our higher cognitive functions and encoding of memories.

But the lifelong, extensive myelination of the human brain also makes it uniquely vulnerable to damage. The myelin model's central premise is that it is the normal, routine maintenance and repair of myelin throughout life that ultimately initiates the mechanisms that produce degenerative diseases like Alzheimer's. That is, the amyloid-beta peptide and the tau peptide, which is also implicated in Alzheimer's, as well as the signature clinical signs of the disease, such as memory loss and, ultimately, dementia, are all byproducts of the myelin breakdown and repair processes.

"The pervasive myelination of our brain is the single most unique aspect in which the human brain differs from other species," said Bartzokis, who is a member of the Laboratory of Neuro Imaging in the UCLA Department of Neurology and a member of UCLA's Brain Research Institute. Myelin is produced by oligodendrocytes, specialized glial cells that themselves become more vulnerable with age.

Bartzokis notes that myelination of the brain follows an inverted U-shaped trajectory, growing strongly until our 50s, when it very slowly begins to unravel as we age. The myelin that is deposited in adulthood ensheaths increasing numbers of axons with smaller axon diameters and so spreads itself thinner and thinner, Bartzokis said. As a result, it becomes more susceptible to the ravages of age in the form of environmental and genetic insults and slowly begins to break down faster than it can be repaired.

The exclusive targeting of the amyloid-beta peptide for many years is understandable because the same genes and enzymes involved in controlling myelination and myelin repair are, ironically, also involved in the production of amyloid-beta proteins. Bartzokis' point is that the amyloid beta may actually develop as a result of the natural process of the repair and maintenance of myelin.

"So the breakdown that leads to Alzheimer's and other age-related brain diseases, such as Parkinson's, may begin much earlier, before the formation of the protein deposits that are used to define these diseases," Bartzokis said.

Most drugs being developed for Alzheimer's are targeting amyloid beta, but little if any clinical improvement is being seen. This is, according to Bartzokis, "similar to cleaning up a house that's been flooded by water but never repairing the actual pipe that created the flood.

"For drug development then, the targets should be much further upstream, earlier in the process before the AB plaques even develop," he said.

Instead of focusing on reducing amyloid beta, Bartzokis argues, the myelin model suggests entirely different approaches to treatment and prevention of Alzheimer's disease that precede plaque formation. With modern brain imaging technology, clinicians could track the dynamic changes taking place in the brain and intercede well before any signs of Alzheimer's are seen.

"With earlier intervention," Bartzokis said, "we could reduce and potentially eliminate the increasingly catastrophic burden of dementia on the individual and their family, the health care system, and our society."


Contact: Mark Wheeler
University of California - Los Angeles

Related biology news :

1. Rethinking the genetic theory of inheritance
2. Rethinking who should be considered essential during a pandemic flu outbreak
3. Neurimmune Therapeutics Announces Advancement of Alzheimers Program into Preclinical Development
4. Paradigm shift in Alzheimerss research: new treatments
5. IRSF announces funding of first clinical trial with disease-modifying therapy for Rett syndrome
6. Insufficient levels of vitamin D puts elderly at increased risk of dying from heart disease
7. Can an over-the-counter vitamin-like substance slow the progression of Parkinsons disease?
8. UH Manoa researcher examines possible implications of daily commute and mosquito-borne diseases
9. Rare genetic disease successfully reversed using stem cell transplantation
10. Mechanism related to the onset of various genetic diseases revealed
11. NIH funds grantees focusing on epigenomics of human health and disease
Post Your Comments:
(Date:10/29/2015)... Calif. , Oct. 29, 2015  The J. ... new report titled, "DNA Synthesis and Biosecurity: Lessons Learned ... the Department of Health and Human Services guidance for ... in 2010. --> ... it also has the potential to pose unique biosecurity ...
(Date:10/29/2015)... NXTD ) ("NXT-ID" or ... the growing mobile commerce market and creator of ... leading marketplace to discover and buy innovative technology ... on StackSocial for this holiday season.   ... a biometric authentication company focused on the growing ...
(Date:10/27/2015)... SAN JOSE, Calif. , Oct. 27, 2015 /PRNewswire/ ... human interface solutions, today announced that Google has adopted ... family of touch controller solutions to power its newest ... Nexus 6P by Huawei. --> ... ecosystem partners like Google to provide strategic collaboration in ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... ... 2015 , ... InSphero AG, the leading supplier of easy-to-use solutions for production, ... to serve as Chief Operating Officer. , Having joined InSphero in November ... and was promoted to Head of InSphero Diagnostics in 2014. There she has ...
(Date:11/24/2015)... HemoShear Therapeutics, LLC, a privately held ... disorders, announced today the appointment of H. ... (BOD). Mr. Watkins is the former president and ... and also served as the chairman of the ... Chairman and CEO of HemoShear Therapeutics. "The combination ...
(Date:11/24/2015)... Nov. 24, 2015 According to two new studies, ... This is something that many doctors, scientists, and public health ... remains: with fewer PSA tests being done, will there be ... Dr. David Samadi, "Despite the efforts made in ... the second leading cancer cause of death in men, killing ...
(Date:11/23/2015)... ... November 23, 2015 , ... Shimadzu Corporation ... its Nexera UC Unified Chromatography system. The award from R&D magazine recognizes Shimadzu’s ... of the year in the analytical and testing category. R&D Magazine chose the ...
Breaking Biology Technology: