Oscar L. Lopez, MD
Director of University of Pittsburgh Alzheimer’s Disease Research Center
Dr. Lopez's research will focus on plasmapheresis (the removal, treatment and return or exchange of blood components) in mice. To date there are no animal models, although it was previously tested in his trial with human subjects with a proven 66% success rate of stopping the progression of Alzheimer’s disease, and in some cases, even improvement; however, the “why” is still unknown. A breakthrough in these results will have implications on the optimal dosage and frequency of the treatment in humans, providing proper treatment as it relates to the varying disease stages.
The Scientist Behind the Mission
Dr. Lopez is the principal investigator of 3 NIH-funded grants as well as co-investigator in another 6 NIH-funded projects. You can read more about Dr. Friedlander's research and background in his University of Pittsburgh's Biography.
"We are trying to create something called compression of mobility... basically we try to make people live healthy, physically and cognitively as long as they can, and as they approach the final days, they will reach those in very good physical and cognitive heath."
- Dr. Oscar Lopez
Explore Lopez's Dementia Research
Dr. Oscar L. Lopez and colleagues previously demonstrated that patients suffering from moderate Alzheimer’s disease (AD) showed improvement in neuropsychological tests of memory, language, and processing speed functions following treatment with therapeutic plasma exchange (TPE). While results from this human clinical trial showed that PE reduced the level of inflammatory biomarkers in blood and was effective in AD patients regardless of cerebrospinal fluid amyloid-beta (Abeta 42), the underlying mechanisms and impact on preserving vascular function remain unclear. Thus, it has been critical to conduct continued research in an AD mouse model that can advance to future human clinical trials.
Since AD pathology is usually associated with vascular dysfunction, Dr. Lopez’s most recent study investigated the therapeutic potential of TPE in preserving vascular reactivity in a young AD mouse model.
Testing Methodology: Bi-monthly TPE began at 6-months of age (mo) in the treatment APP/PS1 group (n=6), exchanging 300-400 μL of plasma from a 2-3 mo donor, wild-type (WT) mouse. The control groups, APP/PS1 (n=6) and WT group (n=5), received no treatment. Wide-field optical imaging (WFOI) at 620nm light was used to assess vascular function. Peak changes from baseline blood oxygenation (OIS-BOLD) were measured (Fig. 1) and images of cortical amyloid plaques were obtained monthly using fluorescence microscopy 6-24 hrs after Methoxy-X04 administration (Fig. 2). To account for mouse variability in plaque accumulation, plaque data were normalized to their value immediately prior to their treatment (i.e., 6 mo data). An analysis of covariance was used to assess statics for vascular reactivity and plaque load.
The results below show a decline in plaque and increased vascular reactivity in mice treated through TPE.
When the study was completed, TPE showed a trend towards reduced cortical plaque load in 8-12 month treated mice and vascular reactivity values measured by blood oxygenation (OIS-BOLD) also showed a trend toward improved function (Fig. 3). Continued studies on old-aged mice will provide additional information about the effects of TPE on AD and vascular function for use in future clinical trials.
Collaborative research findings shared between all current CTF Consortium members can be found here.
