Welcome

Dwight German Lab
Left to right, Yan Deng; Dwight German, Ph.D.; Sayed Zaman; Wenhao Li; Bharathi Gadad; Sarika Singh; Umar Yazdani; Howard Gunn.

Research Interests

Parkinson’s disease

Parkinson’s disease (PD) caused certain dopamine-containing nerve cells in the brain to die. The death of these neurons causes the major symptoms of the disease (i.e., slowness of movement, muscular rigidity and resting tremor). In animals and man, exposure to a neurotoxin (MPTP) causes death of the same population of neurons that die in patients with PD. We have recently created a progressive rodent model of PD using chronic infusion of the MPTP toxin (MPP+) directly into the brain. Unlike acute MPTP models of PD, this progressive model shows increasing neurodegeneration over time. The progressive nature of the neurodegeneration is what occurs in humans with the disease. This model will be useful for testing therapeutics that aim to stop the loss of neurons. Recently, we have found that caffeine treatment markedly reduces the degeneration of the dopamine-containing neurons, which parallels the human observation that caffeine consumption is negatively correlated with the incidence of PD.

Alzheimer’s Disease

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is initially characterized by the inability to form new memories. The neuropathology of AD begins 10-20 years before the memory impairment becomes apparent. We have been working to develop a blood biomarker to identify those that are in the early stage of the disease. Using a combinatorial library of peptoid molecules, antibodies have been identified in the blood of AD patients that are elevated when compared to age-matched normal subjects and those with Parkinson’s disease. These peptoid biomarkers are also elevated in people in the early stage of AD (i.e., those with mild cognitive impairment). Such biomarkers are critical for the development of AD therapeutic drugs because they will enable subjects to be selected for therapeutic testing to determine whether the drugs can block the disease progression.

Certain environmental conditions may contribute to the development of AD. We have recently found that AD patients have elevated levels of a metabolite of the pesticide DDT. This pesticide is used widely throughout the world. We are currently working to determine whether this DDT metabolite plays a causal role in the development of AD neuropathology.

Autism

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by impairments in communication (verbal and nonverbal), social interactions, and stereotyped behaviors/interests. The etiology of ASD is not well understood, though it likely involves both genetic and environmental factors. Immune system dysfunction has been reported in many ASD studies. Systemic immunologic alterations in autistic individuals often have been associated with autoimmunity; in particular, the generation of antibodies reactive against brain and CNS proteins. We are working to identify serum antibody biomarkers for ASD using the same approach that we have used to identify serum antibody biomarkers for Alzheimer’s disease. An ASD blood biomarker would be very useful for early identification and targeted therapeutic intervention.

ASD symptoms become apparent during the time period when children are given vaccinations, leading some people to think that the vaccines and/or the mercury preservative (thimerosal) play a role in symptom onset. We are studying the brains and behavior of non-human primates, exposed to the same 1990 and 2008 childhood vaccination schedules to determine whether neurodevelopmental changes occur. This work is being done in collaboration with the National Primate Research Center at the University of Washington Medical School. Preliminary findings indicate that some of the neuropathological changes observed in post-mortem brains from ASD patients are also found in the vaccine/thimerosal-treated monkeys given the 1990 vaccination schedule.