Synaptic pathology is a prominent feature of Alzheimer's disease and strongly correlates with cognitive impairments. Synaptic damage occurs early in AD development, suggesting that synaptic alterations are a primary event in the progression of AD. However, the underlying mechanisms of synaptic pathology in AD are not completely understood. The main objective of the research awarded the prize was to determine whether presynaptic or postsynaptic compartments of neurons in AD patients are preferentially affected by disease.
Using immunoblotting, immunohistochemistry, and densitometry techniques, Reddy and his colleagues investigated 7 synaptic proteins in a large number of postmortem brains from AD patients and age-matched control subjects. They found a selective loss of both presynaptic and post synaptic proteins in the postmortem brains from the AD patients relative to those from the age-matched control subjects. Of the 7 proteins studied, the presynaptic proteins synaptophysin and rab 3A, and the postsynaptic protein synaptopodin were the most down-regulated. In addition, this paper is the first to report on the loss of synaptopodin in the postmortem brains from AD patients – a finding that beckons further investigation of postsynaptic proteins in AD patients.
P. Hemachandra Reddy was a commonwealth scholar (1990-1993) before receiving his Ph.D. (1994) from University College, London University. He did his postdoctoral training (1995-2000) with Dr. Danilo A. Tagle at the National Human Genome Research Institute, National Institutes of Health, Bethesda, MD. In his post-doctoral research, Dr. Reddy isolated and characterized cDNAs containing polymorphic polyglutamine (CAG)n repeats in the adult human brain cDNA library. In 1998, Dr. Reddy was the first researcher to develop a transgenic mouse model for Huntington's disease (HD) using full-length HD cDNA. This mouse model showed progressive phenotypic behavior and selective neurodegeneration in the striatum and cortex. After his postdoctoral training, Dr. Reddy joined the Neurological Sciences Institute Faculty at Oregon Health & Science University (OHSU) in July 2000 and established the OHSU Neurogenetics Laboratory. The research focus in the Reddy laboratory is on understanding molecular and cellular bases of neurodegenerative diseases. Currently, the Reddy laboratory is focusing on unraveling the connection between amyloid-ß (Aß) and synaptic damage, and Aß and mitochondrial oxidative damage in AD.
Each year the Associate Editors of the Journal of Alzheimer's Disease select the award recipient from among articles published in the previous year's volume. The awardee will receive the Alzheimer Medal, a handsome bronze medal with the likeness of Alois Alzheimer as well as a cash award. Former winners include Lester I. Binder, PhD, Massimo Tabaton, MD, Thomas Wisniewski, MD, Luciano D'Adamio, MD, PhD, Suzanne de la Monte, MD, MPH, Hideo Hara, M.D. and Takeshi Tabira, M.D., Ph.D.
This annual award is generously sponsored by Elan Pharmaceuticals.