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2013 Grants - 2013 Grants - Cedazo-Minguez
Unraveling the Role of Thioredoxin-80 in Alzheimer's Disease Pathology
Angel Cedazo-Minguez, Ph.D.
2013 New Investigator Research Grant
The protein fragment beta-amyloid is a key suspect in Alzheimer's disease. This fragment tends to accumulate into clumps called plaques, which are a hallmark of Alzheimer's. Scientists, however, do not understand the precise mechanisms underlying abnormal beta-amyloid accumulation in the Alzheimer's brain.
During their preliminary studies, Angel Cedazo-Minguez, Ph.D., and colleagues found that the brains of people with Alzheimer's have unusually low levels of an antioxidant compound called thioredoxin-80 (Trx80). They also observed that Trx80 can inhibit the production and toxicity of beta-amyloid. These findings suggest Trx80 may help moderate amyloid production in normal brains; and the loss of Trx80 in Alzheimer's disease may, in part, be responsible or involved in the accumulatio of toxic amyloid clumps.
For their current study, Dr. Cedazo-Minguez and colleagues will develop two animal models—a fruit fly and a roundworm—with human forms of Trx80, beta-amyloid or both. They will then test whether the presence of Trx80 reduces beta-amyloid levels in the animals. The team will also use cultured brain cells to identify exactly how beta-amyloid and Trx80 may bind to and interact with each other. Finally, the researchers will study Trx80 levels in samples of cerebrospinal fluid (the fluid surrounding the brain) from normal people, people with mild cognitive impairment (a condition that often precedes Alzheimer's), and people with Alzheimer's disease. They hope to determine whether abnormal levels of Trx80 in the cerebrospinal fluid may represent an early warning sign for many types of dementia. Collectively, these studies could identify Trx80 as both a target for dementia therapies and a biomarker for diagnosing dementias at their earliest stage.