Veterans Affairs

Alzheimer’s and dementia treatment with CHP-Zinc formulation

Formulation decreases Aβ levels, increases insulin degrading enzyme activity, and enhances learning and memory in an AD mouse model

Medical & Biotechnology

Alzheimer’s disease (AD) neuropathology, which currently affects over 26 million individuals worldwide, is characterized by amyloid-beta (Aβ) containing plaques and neurofibrillary tangles composed of neurofilament and hyperphosphorylated tau protein. Aβ has been demonstrated to be neurotoxic in numerous studies and appears to be responsible for initiating the memory loss associated with AD.

Decreasing Aβ plaque load would presumably reduce the pathology and cognitive difficulties associated with this disease. Aβ levels can be controlled by one or more methods, including regulating amyloid precursor protein (APP) gene expression, regulating APP processing to form Aβ, and controlling or causing Aβ degradation.

CHP plus zinc treatment enhances spatial memory in huAPP transgenic mice. HuAPP transgenic mice (9 months of age) were divided into 2 groups of 3 animals each and treated as follows: control group, animals were given access to H2O alone ad libitum; CHP plus zinc group, animals were given access to 1.0 mg/L CHP + 10 mg/L Zn in H2O ad libitum. Once a month, the animals were subjected to the Morris Water Maze to measure the time it took for the animal to find the platform. Very significant improvement in spatial memory is seen in one month in the CHP plus zinc treated mice. ***P < 0.001 for average ± SEM between CHP plus zinc treatment group and control group by Tukey multiple comparison statistical tests.

Treatments of mammals with thyroid hormone result in down-regulating APP gene expression, possibly via a negative response element in the APP gene. It is also thought that zinc and CHP (Cyclo(His-Pro) a cyclic dipeptide, which is ubiquitous in the central nervous system and is a key substrate of organic cation transporters and is strongly linked to neuroprotection, causes increased activation of the insulin-degrading enzyme (IDE) that causes increased Aβ degradation.

Such therapies may be used for the treatment of AD or dementia. Thus, two biologically safe treatment strategies, which reduce the formation of Aβ, enhance endogenous metabolism of Aβ in vivo, and improve spatial memory, have been developed.

Building on this knowledge, scientists at the Department of Veterans Affairs have formulated a combined composition comprising a thyroid hormone (CHP), and a zinc salt. Such compositions may be used to treat AD, dementia, metabolic syndrome and cerebrovascular diseases. The formulation causes an increased serum level of insulin-degrading enzyme and a decrease in the serum level of Aβ protein. The result is zinc plus Cyclo(His-Pro) that may be beneficial in both reducing Aβ levels and increasing memory function.

 

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