During the 12th annual Helen and Robert Appel Alzheimer’s Disease Research Institute Symposium, scientists and clinicians shared their latest research that anticipates the diagnosis and treated by Alzheimer’s. The symposium was held in the Griffis Faculty Club of Weill Cornell Medicine and gave researchers and members of the community the opportunity to learn and ask questions about new directions in neurodegenerative research. Alzheimer’s disease affects more than 7 million Americans, a number that is expected to increase to 13 million by 2050.
Helen and Robert Appel founded the institute in 2006, asked to take action when two good friends collapsed to the disease two decades ago. “We were determined to do what we could do to make a dent in Alzheimer’s investigation,” said Helen Appel from her and her deceased husband Bob to help find a cure. “We will have to come up with solutions to the problems, and we will do it.”
The symposium does indeed meet at a turning point for Alzheimer’s disease, Dr. Li Gan, director of Helen and Robert Appel Alzheimer’s Disease Research Institute at Weill Cornell. Two disease -modifying therapies are available and the FDA recently approved a blood test for the diagnosis of Alzheimer’s. “This is really a huge deal – many more people can be tested earlier, and it is much more accessible for patients with early symptoms,” said Dr. Gan, who is also the Burton P. and Judith B. Resnick Distingughed Professor in neurodegenerative diseases.
Research on the Appel Alzheimer’s Disease Research Institute uses the momentum by integrating the fundamental discoveries with translational science to prevention and treatment for this devastating disease.
Every discovery we make brings us closer to changing lives. And today’s symposium is a will of the momentum. “
Dr. Li Gan, director of Helen and Robert Appel Alzheimer’s Disease Research Institute at Weill Cornell
New discoveries in disease mechanisms
Over the past 20 years, human genetic studies have given insight into the genes, such as Apoe4, which increase the risk of developing Alzheimer’s disease and the genes that can protect against diseases, which are called resilience all the all. Dr. Gan presented her research that the underlying genetic factors awakens that influence the opportunities to get Alzheimer’s.
She looks at how abnormal forms of the protein -tau accumulate to produce neurofibrillary tangles in the brain cells from many influenced by Alzheimer’s and other neurodegenerative diseases. These tangles disrupt the internal structure of the cell, hinder communication between neurons and contribute to cognitive decline. With high levels of amyloid, the protein that forms plaques and contributes to the Alzheimer’s, patients have a “very modest deterioration”, while the combination of amyloid and tau results in a much steeper decrease in cognitive function, “she said. This difference suggests that some people are in the effects of the disease.
She gave a surprising perpetrator in the congenital immune system of the brain: a path intended to combat viruses. This process revolves around the CGAS gene, which seems to be overactive in Alzheimer’s, which increases harmful inflammation in the brain. When researchers partially removed this gene in laboratory models, the memory and learning improved, even if Tau Tangles was already present.
This positive effect was observed with the resilience of Christchurch mutation on Apoe3-it protected against C-gas activation induced by Tau, the lowering of inflammation and improving synaptic density. Dr.’s team Gan discovered that the braking of C-gas with a medicine could replicate the effects of this resilience. “This gives us a strong motivation that developing the inhibitor will be beneficial for people,” she said.
Dr. Manu Sharma, university teacher Neurosciences at Weill Cornell Medicine, shared his research into how abnormal Tau can spread from Neuron to Neuron in the brain. His laboratory has discovered that Tau aggregates can accumulate in lysosomes, membrane-bound compartments in cells that contain digestular enzymes that break down cellular waste before releasing outside the extracellular space outside. They then started that as soon as Tau was released in the extracellular space, the protein could then sow harmful lumps in adjacent cells.
With the help of neuronal cultures and pre -clinical mouse models, the team of Dr. Sharma demonstrated that TAU aggregates are released in the extracellular space through a process called lysosomal exocytosis, regulated by neuronal activity and cytosolic calcium. By braking lysosomal exocytosis, Dr. Sharma is able to reduce the release of TAU aggregates and to delay their distribution.
Translate research into the clinic
The last speaker, Dr. Valina Dawson, a professor in neurology, neuroscience and physiology at Johns Hopkins University, discussed her findings about Parathantos, a specialized “programmed” cell -red route named after Thanatos, the ancient Greek god of death, as an important cause of nerve cell breakdown that was seen in the disease in the disease in the disease in the disease in the disease in the disease in the disease in the disease. This route includes a molecule called Par, or Poly (ADP-Ribose), which has been raised in patients with the diseases of Alzheimer’s and Parkinson’s. Par can attach itself to DNA and repair breaks, but it also seems to activate Parathantos.
In Parkinson’s, pargregation of the protein A-Synuclein accelerates in toxic Lewy bodies that disturb cellular function. In Alzheimer’s, PAR CO-Lokalizes with Tau and promotes its aggregation. “If you look in cultured neurons, you see that par-tau pathological tau formation in neurons causes more than just Tau himself,” she said.
This finding can open the door for a new therapeutic approach to neurodegeneration. Blocking the par production by inhibiting the enzyme parp can slow or stop dangerous proteinaggregation. Interesting is that when PARP is absent in mouse models of these diseases, there is a protective effect. If PARP inhibitors work in patients with Human Parkinson’s disease as they have in mice, they can protect cells that have already been affected by Parkinson’s and delay the transfer of these harmful proteins.
Another promising direction is an experimental medicine with a small molecule called Paanib-1 that is designed to protect neurons against Parathantos-related cell death in Parkinson’s by selectively blocking the activity of a protein called MIF (Macrofaag migration-in-migrating factor). This medicine and similar connections are being developed for clinical studies. Inhibitors such as Paanib-1 can have therapeutic potential for various disorders where Parthanatos mediated cell death is a contributing factor.
During the final panel, the conversation shifted to how laboratory discoveries could be translated into real-world treatments for people and their diseases. “That is what these scientists do, and I hope that message happened,” said Panelmoderator Dr. Matthew Fink, the chairman of the Neurology department and Louis and Gertrude Feil Professor in Clinical Neurology at Weill Cornell. The discussion continued to return to a central point: Building new discoveries on past efforts, which extended how Alzheimer’s is treated today and possibly finds future healings.
“The researchers who carry out science keep their heads really high and work hard to ensure that the discoveries do not stop, that the clinical tests do not stop and that patients who need our care will get it,” said Dr. Robert A. Harrington, Weill Cornell Medicine Stephen and Suzanne Weiss Dean and Professor in medicine.