Neurodegenerative disease

2012 senior Scholar Award in aging

This project seeks to understand the nature of a material called “aging pigment”, referred to as lipofuscin (“lipo-fusin”), that accumulates in the lysosomes of neurons of normal animals. Lysosomes are small membrane-bounded sacs that contain a high concentration of degradative enzymes that... >> MORE

2011 senior Scholar Award in aging

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that constitutes the major cause of neurological motor impairment in the elderly and as such places an extraordinary burden on the US health care system, at an estimated cost of $25 billion annually. The major risk factor for... >> MORE

2011 senior Scholar Award in aging

The goal of our project is to investigate the impact of the metabolism of phosphoinositides on the neurological manifestations of aging. Phosphoinositides are low abundance membrane phospholipids that have key roles in signaling, membrane trafficking, and cytoskeletal dynamics in all cells.... >> MORE

2010 senior Scholar Award in aging

Neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) are devastating disorders for which there are no known cures. Advancing age is the major demographic risk for these diseases. Thus, as the population ages the prevalence of such diseases increase such that... >> MORE

2010 senior Scholar Award in aging

Sleep is essential for life but is a poorly understood process. Sleep is disrupted during aging and even more so in common diseases that occur during aging such as Alzheimer's disease (AD). Whether normal variations between people in the sleep-wake cycle during mid-life and during aging... >> MORE

2009 senior Scholar Award in aging

It now seems likely that memory involves changes in the strength of synapses. These changes occur during learning and can lead to either an increase or decrease in the strength of synapses. Strong stimulation strengthens synapses, a process called long-term potentiation (LTP). Weaker stimulation... >> MORE

2009 senior Scholar Award in aging

The cause of Alzheimer disease (AD), the most common neurodegenerative disorder of aging, is unclear. It is known that there is an increased accumulation of various proteins in the brain of AD patients (in so-called "amyloid plaques" and "tangles") that are clearly associated... >> MORE

2009 senior Scholar Award in aging

Mitochondria provide the cell with the energy they need to run on, but damaged mitochondria can be highly deleterious to cells. In a large cell like a neuron, getting the right number of mitochondria to the right part of the cell to provide for its needs can be crucial to its health. Clearing... >> MORE

2008 senior Scholar Award in aging
There is a great deal of evidence indicating that microglial cell dysfunction plays a role in a variety of neurodegenerative diseases associated with aging, including Alzheimer's, Multiple Sclerosis, Parkinson's Disease and Stroke. Microglia make up approximately 10% of the cells in the brain. They... >> MORE
2006 senior Scholar Award in aging

There have recently been many exciting advances in research aimed at understanding and ultimately curing devastating neurodegenerative disorders like Alzheimer's disease and Parkinson's disease. In particular, the explosion of molecular genetic technology has led to the identification of genes... >> MORE

2005 senior Scholar Award in aging

During the last year we made a surprising discovery that could lead to a new approach to developing a therapeutic drug to treat Alzheimer's disease. We plan to follow up on this discovery to elucidate the molecular mechanism of Alzheimer's disease in order to develop new molecular targets for... >> MORE

2004 senior Scholar Award in aging

Approximately 10% of individuals over age 65, and nearly half of those over age 85, suffer from Alzheimer's disease. Parkinson's afflicts 1% of people over age 60 and the risk of contracting the disease increases with age. Currently, approximately 4.5 million Americans have Alzheimer's, and more... >> MORE

2003 senior Scholar Award in aging

Aging is invariably associated with reduced neurological function. Moreover, the incidence of acute neurodegenerative disease strongly increases with age. As the average lifespan lengthens due to improvements in medicine and public health, the incidence of devastating neurodegenerative diseases... >> MORE

2002 senior Scholar Award in aging

Alzheimer's disease (AD) is the most common form of dementia in the elderly afflicting over 20 million people worldwide. Overwhelming neuropathological and genetic data support the abnormal accumulation and deposition of a small protein called the Aβ peptide as the critical event in AD... >> MORE

2001 senior Scholar Award in aging

Neuronal degeneration and death are hallmarks of Alzheimer's Disease, but why they occur is still poorly understood. Most workers accept the hypothesis that degradation of a neuronal protein called Amyloid Precursor Protein (APP) is an early event in the pathogenesis of Alzheimer's disease (AD... >> MORE

2000 senior Scholar Award in aging

Alzheimer's disease (AD) is characterized by loss of memory and decreased intellectual function, which result from the loss of function of nerve cells in the brain. Cortical amyloid plaques comprising fibrillar deposits of the amyloid beta [Aβ] proteins Aβ40 and Aβ42 are a... >> MORE

1998 senior Scholar Award in aging

Amyloid Precursor Protein (APP) is the precursor of Aβ, which appears to be critical in the initiation of Alzheimer's disease. Dr. Greengard's research will characterize synaptic organelles that are the major site of APP in nerve terminals.

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1998 senior Scholar Award in aging

Fragments of Alzheimer's polypeptide (APP) are found in senile plaques. Some fragments (Aβ 1-40 and 1-42) appear to be toxic to the brain. Dr. Petsko proposes to identify the enzyme(s) that produce these fragments and then, using Aβ-resistant mutants, determine how the Aβ... >> MORE

2013 new Scholar Award in aging

Aging results in a decline in the integrity and function of cells and tissues.  One reason for this decline is thought to be the inevitable accumulation of misfolded and damaged proteins with time accompanied by the collapse in the cells’ protective protein quality control mechanisms to deal... >> MORE

2012 new Scholar Award in aging

Neurons are highly specialized cells with very long projections called axons, which they use to communicate with one another. Neurons communicate with each other by transmitting signaling molecules. Some of these signaling molecules, and most of the machinery that stores and sends these signals... >> MORE

2009 new Scholar Award in aging
As life spans increase through improvements in medicine and public health, the prevalence of devastating nerve degeneration diseases will inexorably increase to become one of the most severe obstacles to living longer, more fulfilling lives. We are in urgent need of new concepts and approaches to... >> MORE
2008 new Scholar Award in aging
Many neurodegenerative disorders that manifest late in life are caused by mutations that disrupt proper folding of proteins. While young cells often have the capacity to withstand stress caused by misfolded protein overload, old cells frequently succumb to such stress and hence lead to degenerative... >> MORE
2007 new Scholar Award in aging
Adult onset neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS) or Huntington's disease, don't present clinical symptoms until late in life suggesting that the normal aging process plays an important role in determining when affected individuals begin to show disease symptoms.... >> MORE
2007 new Scholar Award in aging

In Parkinson's disease the death of dopaminergic neurons in the brain results in the progressive loss of control of body movement. An estimated 1% of the population aged 65 and older suffers from Parkinson's disease, making it the most common neurodegenerative movement disorder. With this... >> MORE

2006 new Scholar Award in aging
Parkinsonís disease (PD) is the most common movement disorder affecting over one million people in North America alone. It is characterized clinically by resting tremor, slowness of movement, postural instability, and muscle rigidity with these disabilities largely attributed to the extensive loss... >> MORE
2006 new Scholar Award in aging
Alzheimer's disease is one of the most dreaded and common causes of dementia in elderly humans. Recent clinical evidence has identified disease and dysfunction in small blood vessels in the brain as being intimately linked to the development and severity of Alzheimer's disease. It remains unclear,... >> MORE
2004 new Scholar Award in aging
Synaptic stability is likely to be critical for long term information storage and normal memory function. In Alzheimer's disease (AD), synapses have been shown to be one of the earliest neuronal structures to be affected and their loss could be a very important factor in the cognitive decline... >> MORE
2003 new Scholar Award in aging
Prion diseases belong to a large group of neurodegenerative disorders occurring in the elderly, such as Alzheimer's disease and Parkinson's disease. Like other neurodegenerative disorders, prion disease can be manifested as a sporadic or inherited disease. However, prion diseases can also be... >> MORE
2003 new Scholar Award in aging

In Alzheimer's disease, a chronic inflammatory response to β-amyloid has been proposed to underly neuro-degenerative pathology. Central to this hypothesis is the observation that microglia are recruited to, and accumulate at, sites of β-amyloid deposition. These cells produce... >> MORE

2002 new Scholar Award in aging

Human gamma-secretase is a large membrane protein complex catalyzing a novel reaction of intramembrane proteolysis. This activity is important in a number of cellular signaling pathways. There are three known gamma-secretase components, presenilin, nicastrin and beta-catenin. Mutations in... >> MORE

2002 new Scholar Award in aging

Progressive loss of neurons in the brain is a hallmark of many neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. The only known risk factor for the majority of such patients is aging. Nonetheless, most people do not develop these disorders during aging, so other... >> MORE

2002 new Scholar Award in aging
Alzheimer's disease (AD) is the most common form of age-related dementia and one of the most serious health problems in the U.S. Most cases of early-onset familial Alzheimer's disease (FAD) are caused by mutations in two related genes, known as presenilin 1 and 2 (PS1 and PS2). Deciphering the... >> MORE
2001 new Scholar Award in aging

Neurodegenerative diseases share many molecular and pathological similarities, yet no unifying explanation exists to explain how and why they arise. We propose that defects in a novel biological system underlie development of these disorders, and will test this hypothesis by investigating a... >> MORE

2000 new Scholar Award in aging
In vivo analysis of the role of tau in neurodegeneration >> MORE
2000 new Scholar Award in aging

The transgenic and gene knockout technology has proved to be a powerful system to elucidate in vivo functions of target genes and to establish mouse models of human diseases. However, the conventional approach introduces modifications in mouse germline, which may lead to adverse effects... >> MORE

1999 new Scholar Award in aging

As we age, neurons in our brain tend to accumulate abnormal protein. The same process occurs in degenerative diseases of aging such as Alzheimer and Parkinson diseases, but at a much faster rate. Our research aims to identify the various ways that abnormal protein accumulation compromises the... >> MORE

1999 new Scholar Award in aging

Alzheimer's disease (AD) occurs when large numbers of neurons - the cells which make up the brain, die over many years. These cells are in the areas of the brain which are responsible for forming and storing memories and for performing higher thought processes. This is why AD affects memory and... >> MORE

1998 new Scholar Award in aging
Dr. Golde compares Alzheimer's disease (AD) to atherosclerosis. Both are diseases associated with aging, both have strong genetic components, and both are diseases of deposition. Atherosclerosis involves deposition of cholesterol within blood vessels, which damages the cardiovascular system.... >> MORE
1998 new Scholar Award in aging

Apoptosis is a genetically regulated form of cell death which is critical for the normal development and adult function of multicellular organisms. Inappropriate activation of apoptosis also contributes to the neuronal cell loss associated with acute brain injuries such as stroke, and in age-... >> MORE