Research Findings

We are pleased to provide updates from previous CART Fund grant recipients outlining the results of their research. We are encouraged by these researchers’ continued efforts to provide cutting-edge research data at world-class facilities in the United States thanks to grants from The CART Fund.

Final Reports from Grant Recipients:


Dr. Wenjie Luo (Cornell University) was the recipient of a $100,000 grant from The CART Fund in 2015.

Investigating the role of microglia in tau clearance in Alzheimer’s Disease

During these three years supported by the CART Fund, we have performed the experiments as proposed in the original plan and obtained extensive knowledge about how microglia degrade pathological tau based on the following scientific results. In our original proposal, we planned to investigate the mechanism how brain phagocytic cell microglia play a role in the brain clearance of tau, a pathologic protein that can spread from neuron to neuron and form deadly neurofibrillary tangles in Alzheimer’s Disease (AD). The ultimate goal of this research project is to search for therapeutic agents that can enhance the tau-degrading activity of microglia, thus reducing tau pathology and preventing cognitive decline in AD patients. During these funded years, we have made scientific discoveries about the mechanism how pathologic tau is internalized and degraded by microglia. We also identified the activation conditions as well as genetic factors that regulate this tau degradation process in microglia. Finally, we have collected data showing that brain microglia approach pathologic tau injected into the mouse brain (see figure to right).

We deeply appreciate the tremendous help provided by The CART fund to help us initiate and extend this project. The scientific observation and conclusion are significant for the AD basic research and also impact greatly in AD therapeutic study.


Posted December 17, 2018



CART-funded Computational Research Identifies Potentially Effective Drug Combinations for Alzheimer Disease Treatment:

Dr. Thomas Anastasio (University of Illinois) was the recipient of a $50,000 grant from The CART Fund in 2016.

Alzheimer Disease (AD) remains the leading neurological killer, and “the amyloid hypothesis” remains the leading theory of AD. “Amyloid-beta” is the abnormal protein fragment that accumulates in AD brains and that composes the “amyloid plaques” that are found in AD brains.  The amyloid hypothesis says that amyloid-beta causes AD – but it’s wrong! Treatment strategies aimed at reducing amyloid-beta don’t work!

These and other observations show that amyloid-beta is not the only factor that underlies AD. Instead, research shows that AD is “multifactorial” in that it is caused by many different factors, not just amyloid-beta. And because AD is multifactorial, it probably should be treated with combination therapies that target multiple factors. But this poses a problem because the design of combination therapies to treat multifactorial diseases is highly complex. One project funded by the CART foundation addressed this problem.

This computational project proceeded in three stages. The first was to create a computer model of the interactions between many of the key factors that are known to underlie AD. The second was to analyze an extensive database containing data on real AD patients, which also included lists of all the drugs they took. Fortunately, the patients in the database took commonly prescribed drugs in many different combinations, so the third stage was to see if the benefits to the patients of specific combinations of drugs could be correlated with predictions of the efficacies of those same drug combinations from the computer model.

Statistical analysis showed that the database benefits and the predicted model efficacies were significantly correlated! That meant that the computer model was picking up something real about the complex, multifactorial, pathological processes that underlie AD. The main payoff was that the agreement between the database and the model could be used to identify new drug combinations that might actually be effective in treating AD, and they involve commonly used drugs that elderly people already take.

The approach identified many potentially effective combinations, but combinations of certain drugs rose to the top. They included the NSAIDs ibuprofen (and similar drugs) and aspirin, along with drugs that are commonly used to treat high blood pressure. This CART funded project suggests that these combinations should be explored experimentally and/or clinically to see if they really can be effective weapons in the fight against AD.

Posted December 3, 2018



Dr. Frank Sharp (University of California at Davis) was the recipient of a $125,000 grant from The CART Fund in 2016.

We were the first to propose that lipopolysaccharide (LPS, found in the wall of all Gram-negative bacteria) could play a role in causing sporadic Alzheimer’s disease (AD). This is based in part upon recent studies showing that: Gram-negative E. coli bacteria can form extracellular amyloid; bacterial-encoded 16S rRNA is present in all human brains with over 70% being Gram-negative bacteria; ultrastructural analyses have shown microbes in erythrocytes of AD patients; blood LPS levels in AD patients are 3-fold the levels in control; LPS combined with focal cerebral ischemia and hypoxia produced amyloid-like plaques and myelin injury in adult rat cortex. Moreover, Gram-negative bacterial LPS was found in aging control and AD brains, though LPS levels were much higher in AD brains. In addition, LPS co-localized with amyloid plaques, peri-vascular amyloid, neurons, and oligodendrocytes in AD brains. Based upon the postulate LPS caused oligodendrocyte injury, degraded Myelin Basic Protein (dMBP) levels were found to be much higher in AD compared to control brains. Immunofluorescence showed that the dMBP co-localized with β amyloid (Aβ) and LPS in amyloid plaques in AD brain, and dMBP and other myelin molecules were found in the walls of vesicles in periventricular White Matter (WM). These data led to the hypothesis that LPS acts on leukocyte and microglial TLR4-CD14/TLR2 receptors to produce NFkB mediated increases of cytokines which increase Aβ levels, damage oligodendrocytes and produce myelin injury found in AD brain. Since Aβ1-42 is also an agonist for TLR4 receptors, this could produce a vicious cycle that accounts for the relentless progression of AD. Thus, LPS, the TLR4 receptor complex, and Gram-negative bacteria might be treatment or prevention targets for sporadic AD.

Posted October 23, 2018



Dr. Yueming Li (Memorial Sloan Kettering Cancer Center, NYC) was the recipient of a $250,000 grant from The CART Fund in 2016.

Alzheimer’s disease (AD) is characterized by an aggregation of toxic proteins that build up in the brain. Normally, a process called autophagy allows cells to rid themselves of any “garbage” they hold. We define that garbage as proteins that are unnecessary or dysfunctional components.

When people have AD, the autophagy process fails with two specific proteins, toxic amyloid beta plaques and tau tangles. The cells cannot rid themselves of these proteins. In fact, we can see the cumulative toxicity when we examine the brain of a patient with AD who has passed away.

AD is caused by progressive brain cell death over time. We believe that AD, as well as other neurodegenerative disorders, can be treated by addressing breakdown in the cells’ autophagic pathways. If the pathways can return to functioning properly, the cells may able to engage in their own housekeeping and free themselves of the damaging detritus.

My team is looking at ways to clear the autophagic pathways in these cells. Because of advanced technologies, we can use chemical libraries to screen for and identify existing drug molecules that promote the proper function of these cleaning pathways.

With this generous grant, we have identified such molecules. We have also synthesized the molecules because in doing so we can improve their drug properties.

As we move forward, we’re continuing to develop this class of molecules as drug candidates to further understand, and possibly treat, AD. Our progress has brought us closer to our goal of bringing relief to individuals and families living with this difficult and progressive neurological disease.

Posted October 15, 2018