Alzheimer’s Disease

Alzheimer’s disease is a complex and an irreversible neurodegenerative disorder of the elderly, characterized by progressive cognitive decline and loss of memory.

Alzheimer’s disease is considered to be the second most feared disease after cancer. This is because memory loss occurs to such an extent that the affected patients can’t recognize their own family members and friends and they may completely depend on nursing care as the disease advances. It is estimated that nearly 5.3 million patients in the United States alone or 35.6 million patients worldwide suffer from Alzheimer’s disease. Because there is no effective treatment available now to at least slowdown Alzheimer’s disease, and also because of gradual increase in life span of human beings due to improved health care, by 2050, 115.6 million AIDS & Other Infectious Diseasespeople worldwide are predicted to suffer from Alzheimer’s disease. The current FDA approved drugs are useful only for temporary symptomatic relief, but they cannot reverse or at least slow down the disease from further deterioration since they were not designed to treat the underlying cause of the disease.

Alzheimer’s disease is pathologically characterized by the presence of neurofibrillary tangles inside the neuron, the fundamental units of the brain. Tangles are formed as a result of alteration in a protein called Tau which affects transportation of essential materials within the neuron. The disease is also characterized by the accumulation of toxic protein called amyloid beta outside the neuron. The aggregation of these toxic proteins is believed to be responsible for loss of synapses (junctions), the points where two neurons communicate with each other. There are an estimated 200 billion neurons in an adult human brain, and each neuron can make one thousand to ten thousand connections with other neurons via these synapses. Thus within human brain there are an unimaginable number of trillions of connections that far exceeds the number of stars in 1500 galaxies in the universe. With the gradual loss of these synapses, the complex network of neurons, which is indispensable for proper functioning of the brain, are lost in the Alzheimer’s brains leading to loss of memory, poor judgment and other debilitating conditions affecting day to day life of Alzheimer’s patients.

Mitochondria convert molecules derived from food to those that provide energy to the cell. In the process small amounts of free radicals are produced, however under conditions where mitochondria are excessively stressed they produce large amounts of free radicals, cause severe damage and can lead to the death of the cell. As people age our cells produce more of these free radicals and recent studies have provided evidence of induction of free radicals by amyloid beta a peptide long associated with Alzheimer’s disease. Nerve cells in AD patients are less efficient at generating energy and proteins involved in energy production in the mitochondria are often damaged by free radicals.

The ultimate goal is to develop cause-based therapy that will modify the disease process as a whole and not just treat symptoms.

Principal Investigators are focusing on the following research projects on Alzheimer’s Disease:

  • Identify and characterize those proteins which are responsible for producing amyloid beta peptide.
  • Identify and characterize those molecules which mediate loss of synapses in Alzheimer’s disease.

Dr. Colette Dooley has developed fluorescent sensors for some of the free radicals which allow a visual representation of the production of free radicals in normal and impaired mitochondria. She is interested in the patterns of free radical production and the conditions which they are induced and we are looking for compounds that prevent the production or limits the damage caused by these free radicals

Dr. Madepalli Lakshmana's primary research interest is to understand molecular mechanism for the reduced synaptic connections in Alzheimer’s disease (AD) leading to loss of memory, a seminal feature of AD.