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Alzheimer's disease causes a progressive dementia that currently affects over 35 million individuals worldwide and is expected to affect 115 million by 2050 (ref. 1). There are no cures or disease-modifying therapies, and this may be due to our inability to detect the disease before it has progressed to produce evident memory loss and functional decline.(More)
Parkinson's disease, an age-related neurodegenerative disorder, is characterized by the loss of dopamine neurons in the substantia nigra, the accumulation of α-synuclein in Lewy bodies and neurites, and neuroinflammation. While the exact etiology of sporadic Parkinson's disease remains elusive, a growing body of evidence suggests that misfolded α-synuclein(More)
A recent history of failed clinical trials suggests that waiting until even the early stages of onset of Alzheimer's disease may be too late for effective treatment, pointing to the importance of early intervention in young people. Early intervention will require markers of Alzheimer's risk that track with genotype but are capable of responding to(More)
Parkinson’s disease (PD) is the second most common age-related neurodegenerative disorder typified by tremor, rigidity, akinesia and postural instability due in part to the loss of dopamine within the nigrostriatal system. The pathologic features of this disorder include the loss of substantia nigra dopamine neurons and attendant striatal terminals, the(More)
The midbrain dopamine system mediates normal and pathologic behaviors related to motor activity, attention, motivation/reward and cognition. These are complex, quantitative traits whose variation among individuals is modulated by genetic, epigenetic and environmental factors. Conventional genetic methods have identified several genes important to this(More)
The properties of depolarization-evoked calcium transients are known to change during the maturation of dissociated cerebellar granule neuron cultures. Here, we assessed the role of the calcium-induced calcium release (CICR) mechanism in granule neuron maturation. Both depletion of intracellular calcium stores and the pharmacological blockade of CICR(More)
Brain-derived neurotrophic factor (BDNF) appears to be both regulated by and a regulator of epileptogenesis. In the flurothyl (HFE) model of kindling mice exposed to successive flurothyl trials over 8 days express a rapid, long-lasting reduction in generalized seizure threshold and a more slowly evolving change in seizure phenotype in response to subsequent(More)
The molecular profiling of peripheral tissues, including circulating leukocytes, may hold promise in the discovery of biomarkers for diagnosing and treating neurodegenerative diseases, including Alzheimer's disease (AD). As a proof-of-concept, we performed a proteomics study on peripheral leukocytes from patients with AD both before and during treatment(More)
PURPOSE Juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten disease, is a pediatric neurodegenerative disease characterized by vision loss, seizure activity, cognitive decline, and premature death. Discovery of the Batten disease-related gene, CLN3, led to creation of a Cln3 protein-deficient mouse model (Cln3-/-), which recapitulates some of the(More)
In the central nervous system, chemokines are primarily mediators of inflammatory processes. Their receptors, in particular, CXCR4 and CCR5, serve as co-factors along with CD4 that permit Human immunodeficiency virus-1 (HIV) infection. Moreover, experimental evidence has shown that CXCR4 and CCR5 mediate the neurotoxic effects of the HIV envelope protein(More)