Education: University of Leeds, England, l969-l974
B. Sc. (Hons., lst class, in Biochemistry), l97l
Ph. D., Biochemistry, l974
Albert Einstein College of Medicine, Bronx, New York,
Department of Pathology and Neuroscience,
Assistant Professor. 07/l8/77-06/30/8l
Associate Professor. 07/0l/8l-06/30/86
Professor. 07/01/86 to-date
Phone: (516) 562-3492
Email: pdavies@nshs.edu

Plaques and tangles may be the sign posts for Alzheimer's disease, but Peter Davies, PhD, has discovered the road itself - and it is a pathway that scientists in the field have missed after decades spent exploring the terrain of the diseased brain. Dr. Davies runs a large Alzheimer's research center and his scientists come at the disease from all sides. Their work may well change the way people think about Alzheimer's disease. Today, most of the attention goes to the amyloid-filled plaques and tau-laden tangles. But Dr. Davies said that Alzheimer's disease may be a process of cell cycle division gone wild.

He has evidence that the switch that drives the cell cycle of neurons, which is a one-time event when the neuron is born, is somehow tripped and reactivated late in life. It is this catastrophic occurrence that sets the stage for cell death. "Neurons don't divide but for some reason the machinery for cell division is turned on in the brains of Alzheimer's patients," Dr. Davies said. "These are differentiated neurons that are not built to divide. The machinery is making enzymes and proteins that the cells are not supposed to see, and this just isn't good for the cell." They designed an experiment to turn on the cell cycle in laboratory models. They put a viral oncogene into differentiated neurons and watched as pathological events unfolded. If Dr. Davies is right, it's the unbridled and unexpected cell division that is the initial event in the disease process. Many other teams have replicated the finding.

Dr. Davies is also known for his work on the tau protein that accumulates in the damaged neurons of Alzheimer's patients. His studies have led him to rethink the relationship tau plays in the diseased brain. "Alzheimer's doesn't start with tau or amyloid," Dr. Davies said. "They are the sign posts that tell us that the cell cycle has been turned on." That would mean a drug that stops this machinery could prevent both of these pathological events. More importantly, it may stop the brain cells from dying. The goal of the research lab is to develop and test new treatments for Alzheimer's disease.

Dr. Davies and his collaborators have already identified a marker in cerebrospinal fluid that can distinguish Alzheimer's disease from normal aging, as well as discriminate between Alzheimer's and other forms of dementia. The overall goal of Dr. Davies' research is to develop treatments to slow or halt the progression of Alzheimer's disease. To accomplish this, he and his team have established a program of research into the basic biology of the disease in the human brain. They are especially interested in biochemical events that occur early in the course of the disease and modify the two major proteins involved - tau and the amyloid precursor protein. They have established clear ideas of the biochemical pathways that lead to the incorporation of tau into neurofibrillary tangles and designed several projects to better understand amyloid deposition in plaques. This research involves direct examination of human brain tissue and extensive work on transgenic mouse models of aspects of the disease, as well as molecular and cell biology.

As new treatments for Alzheimer's disease are discovered by work in Dr. Davies' lab and by other groups, there will be an increasing need for translational research to examine the effects of these treatments in human patients. The Litwin-Zucker center has established a clinical research group that will use biological markers, imaging techniques and sophisticated neuropsychological assessments to better define the effects of these treatments on the course of the disease. Dr. Davies is internationally known for his work in unraveling the mystery of Alzheimer's disease.

Basic Science Research
Our goal is to understand the basic biological processes that happen in the brain in the earliest stages of Alzheimer's disease. These processes set in motion a cascade of changes that lead to the characteristic hallmarks of the disease, neuritic plaques, neurofibrillary tangles and cell death. An improved understanding of the cellular and molecular nature of these changes will lead to the discovery and development of drugs to block the progress of the disease in it's earliest stages. The team is already actively involved in drug discovery programs, aimed at blocking some of the earliest changes detectable in Alzheimer's disease. Ongoing work to develop more accurate early detection of the disease will prove vital to treatment of early stage disease. We are also very committed to discovering what factors make the brains of some individuals more susceptible to Alzheimer's disease. As these factors are better defined, efforts to prevent the disease can move forward.

Neuronal degeneration in Alzheimer's disease (AD). This research focuses on the molecular basis of the neuronal degeneration that occurs in Alzheimer's disease. The research team is studying the early biochemical changes that lead to the formation of two classic lesions of the AD brain, the senile plaques and the neurofibrillary tangles. The team has developed genetic, molecular and cell-biology methods for the purification and analysis of the core components of these lesions, the amyloid-beta peptides and the hyperphosphorylated tau. The team has also recently discovered a novel candidate gene involved in late-onset AD.

The Endocannabinoid System in Alzheimer's Disease. The body produces substances called endocannabinoids that are closely related in structure and function to the active ingredient in marijuana, and may have effects on immunity and memory. This study examines the link between the cannabinoid system and Alzheimer's disease through the development of an Alzheimer's mouse model deficient in cannabinoid signaling.

Molecular Studies in Alzheimer's Disease. Tau is an important protein found in neurons. Abnormal tau aggregates into neurofibrillary tangles, one of the hallmarks of AD. In molecular experiments in living cells, the study team is examining the effects of abnormal tau on different cell functions, and how different drugs may impact tau protein. In another set of studies, the team is examining every protein found in the brain using a method based on cutting edge microarray technology. This technology enables the study of abnormal expression of proteins in tissue from people at high risk for Alzheimer's disease, and people with the disease. The team hopes to identify novel brain chemicals that are involved in the pathological processes that result in neurodegenerative disease like Alzheimer's disease and also to identify factors that protect people from developing the disease. This will help to discover brain chemicals that are treatment targets for new drugs.

Selected Publications:

Hampel H, Buerger K, Zinkowski R, Goernitz A, Teipel SJ, Andreasen N, Sjogren M, DeBernardis J,  Kerkman D, Ishiguro K, Ohno H, Vanmechelen E, Vanderstichele H, McCulloch C, Möller HJ, Davies P, Blennow K. Measurement of phosphorylated tau epitopes in the differential diagnosis of Alzheinmer's disease - a comparative CSF study, Archives of General Psychiatry , 61; 95-102, 2004

Conrad C. Vianna C. Schultz C. Thal DR. Ghebremedhin E. Lenz J. Braak H. Davies P. Molecular Evolution and Genetics of the Saitohin Gene and tau haplotype in Alzheimer’s Disease and Argyrophilic Grain Disease. J Neurochem, 89, 179-188, 2004.

Bargorn S. Davies P. Mandelkow E. Tau paired helical filaments from Alzheimer’s disease brain and assembled in vitro are based on beta-structure in the core domain. Biochemistry , 43, 1694-1703, 2004.

Andorfer CA. Acker CM. Kress Y. Hof PR. Duff K. Davies P. Cell Cycle Re-entry and Cell Death In Transgenic Mice Expressing Non-Mutant Human Tau Isoforms. J Neurosci, 25; 5446-5454, 2005.

Marambaud P. Zhao H. Davies P. Resveratrol promotes clearance of Alzheimer’s disease amyloid-beta peptides. J Biol Chem, 280, 37377-37382, 2005.

de Leon MJ. DeSanti S. Zinkowski R. Mehta PD. Pratico D. Segala S. Rusinek  H. Lia J. Tsui W. Saint Louis LA. Clark CM. Tarshish C. Lia Y. Lair L. Javier E. Rich K. Lesbre P. Mosconi L. Reisberg B. Sadowski M. DeBernadis JF. Kerkman DJ. Hampel H. Wahlund  L-O. Davies P. Longitudinal CSF and MRI biomarkers improve the diagnosis of mild cognitive impairment. Neurobiology of Aging 27, 394-401, 2006.

d’Abramo C.Ricciarelli R. Pronzato MA. Davies P. Troglitazone, a Peroxisome Proliferator-activated Receptor-gamma  agonist, decreases tau phosphorylation in CHOtau4R cells. J. Neurochem, 98, 1068-1077, 2006.

 Park KHJ. Hallows JL Chakrabarty P Davies P Vincent I. Conditional neuronal SV40 T Antigen expression induces Alzheimer-like tau and amyloid pathology in mice. J Neurosci, 27, 2969-2978, 2007.

Espinoza M. de Silva R. Dickson DW. Davies P. Differential Incorporation of Tau Isoforms in Alzheimer’s Disease. Journal of Alzheimer’s Disease, 14, 1-16, 2008.