Environmental Impacts on Risk for Dementia & Alzheimer's Disease
The Purdue Institute for Integrative Neuroscience (PIIN) hosted its first virtual workshop to create interdisciplinary research teams focused on tackling major problems in Alzheimer’s disease and related dementias (ADRDs) on August 12, 2020. The workshop was focused on 'Environmental impacts on risk for dementia and Alzheimer’s disease’. The agenda included welcoming remarks from Dr. Chris Rochet, the John and Donna Krenicki Director of PIIN, followed by presentations from Dr. Aaron Bowman, Professor and Head, School of Health Sciences, Dr. Jason Cannon, Associate Professor, School of Health Sciences, and Dr. Julia Chester, Professor, Department of Psychological Sciences. The virtual workshop, attended by more than 60 faculty members, involved five breakout sessions where various faculty members shared their research ideas and discussed potential funding opportunities. The presentations and a summary of the breakout session discussions are below.
Presentations
ADRD Breakout Sessions Summary
A stem cell model for Alzheimer's disease (hosted by Dr. Aaron Bowman)
The Bowman lab is collaborating with Dr. Liana Apostolova (Indiana University School of Medicine) as part of a multisite trial to identify individuals with early-onset (but not familial) Alzheimer's disease (AD) in the context of the known genetic risk factors for familial AD. In this process, the Apostolova group collects lymphocytes, and Dr. Bowman's lab is generating STEM cell lines from the samples collected from early-onset AD individuals. PIIN and Dr. Bowman’s lab are working on an MTA to allow Purdue investigators interested in these cell lines to have access to them for research purposes. The group discussed multiple aspects of the process of developing and studying such stem cell lines. The PIIN Neuroscience Core is developing methods to carry out CRISPR-mediated gene editing in these stem cell lines. Faculty members expressed interest in understanding cellular mechanisms of neurodegeneration (e.g., cytoskeleton disruption or perturbations of membrane trafficking) of AD as potential future research work.
Environmental and epidemiological factors of AD (hosted by Dr. Riyi Shi)
The group expressed interest in studying the effects of manganese in neurodegeneration. There was interest in assessing neurotoxic concentrations of manganese and understanding how the metal ion crosses the blood-brain barrier. Welders and steel workers get the most exposure to metals used in their occupation through the nasal cavity. For others, exposure is probably mostly through the diet, which is a less direct route of exposure. Dr. Sereno is interested in studying executive function like attention and memory and has approached this problem in a monkey animal model by recording in different parts of the cortex. She has also tested humans, typically using eye trackers, to perform simplified tasks. Dr. Sereno’s human cohorts consist of individuals without disease as well as clinical populations, including developmental disorders like autism, neurological diseases like Parkinson's, and psychiatric disorders like schizophrenia. The group discussed the possibility of future collaboration with Dr. Ellen Wells, with the aim of using the eye tracker and other tests to study individuals with neurodegenerative diseases. Dr. Riyi Shi is interested in studying how TBI can be a factor that could lead to AD. The Shi lab is also interested in understanding the role of environmental factors such as manganese and acrolein levels. Studies have shown that Indiana has a high level of acrolein in the ambient air. It is capable of directly causing protein aggregation and triggering oxidative stress. The group also discussed various topics regarding the blood-brain barrier, cerebral spinal fluid production, or interstitial fluid production in AD. More about this topic will be discussed in greater detail in the next workshop.
Preclinical behavioral assessment of environmental impacts on ADRD risk (hosted by Dr. Julia Chester)
The Chester lab is interested in understanding how alcohol and alcohol-related behaviors could increase AD risk. Her lab focused on animal models and stress-related modeling, and how environmental impacts can accumulate over the lifetime, whether exposure to chemicals, drugs like alcohol, stress, or traumas. Dr. Chester and Dr. Cannon have been working on a project related to alcohol and Parkinson's disease (PD) and environmental toxins and psychiatric disease risk, particularly psychosis. The team is trying to find a genetic model in combination with the environmental exposure model that would produce a phenotype that would be relevant. The group expressed interest in using preclinical models for in utero alcohol exposure and how that might impact the progression of neurodegenerative diseases such as AD across the lifespan. Dr. Allison Schaser, is interested in understanding the pathophysiology of age-related synucleinopathies and their role in neurodegeneration such as PD. Drs. Chester and Schaser began exploring potential research collaborations. The group also discussed epigenetic mechanisms with respect to alcohol-related risk factors. The team will be using the PIIN Animal Behavior Core Facility to perform behavioral tests and test various animal models.
Dietary toxins and AD (hosted by Dr. Jason Cannon)
The majority of the discussion focused on the role of beta-secretase 1 (BACE1) in Alzheimer’s disease, both in response to environmental exposures and as a therapeutic target. Heterocyclic aromatic amine neurotoxicity relevant to AD was discussed and how it might be mediated through BACE1. An interesting effect that opioid receptors have in regulating BACE1 was brought to light as a potential source of collaboration by Richard van Rijn. This is one very interesting angle, how could those prescribed or abusing opioids differentially respond to AD relevant insults through BACE activity alterations? Blood-brain-barrier import/export mechanisms were also discussed with Greg Knipp.