Program of Research

Jennifer Court

For my three papers, I found the main author to be Jennifer Court, who transitioned to having her own lab. Jennifer is associated with Newcastle University, and most of her research seems to focus on investigating the cholinergic pathways in people with AD and PD. She seems to be far along in her career with publications stretching as far back as 1986. All three papers are concerned with nicotinic receptors and their function within patients with AD, PD, AND DLB.

A common symptom of AD is the build up of B-amyloid plaques in the brain. In this study, the researchers treated mice that were carrying an amyloid precursor protein. These mice were treated with nicotine drinking fluid to see if a reduction in in these plaques will occur. They began the study with nine month old mice, and had an estimated daily intake of 25-35mg of nicotine. The study also utilized a control group of mice that received a sucrose solution. The mice were then killed by cervical dislocation in order to perform an analysis of their brain. They found that both male and female rats that received the nicotine solution saw a reduction in plaques and plaque density in the frontoparietal, hippocampus, and olfactory tract. Males also had a more dramatic reduction in plaque in the frontal cortex. 

Citation: Nordberg, Agneta, et al. "Chronic nicotine treatment reduces β‐amyloidosis in the brain of a mouse model of Alzheimer's disease (APPsw)." Journal of neurochemistry 81.3 (2002): 655-658.

It is known that nAChR binding decreases with age, yet it has not yet been determined what specific subunits deteriorate to contribute to symptoms of AD. This study is the first to utilize immunoprecipitation techniques to study the subunit composition of nAChRs, and investigates the loss of nAChR subunits that contribute to difficulty binding in the temporal cortex and striatum. Tissue was obtained with patients' consent, and past criteria indicated the presence of dementia or PD. The study found that alpha4 and beta2 containing receptors are the most dominant nAChRs in the neocortex and striatum. They concluded that therapies targeting nAChRs can best treat patients with AD, PD, and DLB. 

Citation: Gotti, Cecilia, et al. "Selective nicotinic acetylcholine receptor subunit deficits identified in Alzheimer's disease, Parkinson's disease and dementia with Lewy bodies by immunoprecipitation." Neurobiology of disease 23.2 (2006): 481-489.

This current study aims to understand the relationship between alphaBGT and nicotine binding in the thalamus in patients with schizophrenia and DLB. 12 samples of brain tissue were obtained from patients that meet the diagnostic criteria, and 12 control cases that were free of schizophrenia and DLB. Nicotine receptor autoradiography was then analyzed and an average value for the intensity of binding in the nucleus was measured. They found that in both patients with schizophrenia and DLB, average values of alphaBGT were greatly reduced in the reticular nucleus. They also found a slight loss of binding in the lateral dorsal nucleus. 

Citation: Court, Jennifer, et al. "Neuronal Nicotinic Receptors in Dementia with Lewy Bodies and Schizophrenia: α‐Bungarotoxin and Nicotine Binding in the Thalamus." Journal of neurochemistry 73.4 (1999): 1590-1597.

Within the three papers I found, they tend to become more specific. The papers that observed the amyloid plaques in rats and the aBGT in the thalamus were much more specific than the paper where she wanted to determine the range of nAChR subunits contribute to symptoms of AD.