Current Alzheimer Research - Volume 4, Issue 3, 2007

Anesthesia and surgery have been reported to produce long-term cognitive problems, and to accelerate neurodegenerative disorders in the elderly. In previous work, we found that inhaled anesthetics enhance fibril formation and cytotoxicity of amyloid β peptide. In this work we show that the inhaled anesthetics halothane (2-bromo-2-chloro-1,1,1- trifluoroethane) and isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromet Read More

Alzheimer's disease (AD) involves neuronal loss and reduction of synaptic density in specific brain region. Some of the neuronal deaths are associated with excitotoxicity. We previously reported that amyloid β-peptide (Aβ) induced release of N-methyl-D-aspartate receptor (NMDA-R) co-agonists, including glutamate and D-serine. The induction of D-serine production by Aβ involves transcriptional and/or translational regul Read More

For centuries, extracts from the leaves of the Ginkgo biloba tree have been used as Chinese herbal medicine to treat a variety of health disorders. The standardized Ginkgo biloba extract EGb 761 was marketed in France and Germany 30 years ago for various vascular and cerebral deficits and is now classified as a food supplement in the United States. EGb 761 is currently the focus of phase-III clinical trials, GEM and GuidAge st Read More

One of the earliest manifestations of Alzheimer's disease (AD) is the characteristic inability of affected individuals to form new memories. Memory impairment appears to significantly predate the death of nerve cells, implying that neuronal dysfunction is responsible for the pathophysiology of early stage AD. Mounting evidence now indicates that soluble oligomers of the amyloid-β peptide (Aβ) are the main neurotoxins that lea Read More

Previous research suggests separate neural networks for implicit (non-declarative) and explicit (declarative) memory processes. A core cognitive impairment in mild to moderate Alzheimer's disease (AD) is a pronounced declarative memory and learning deficit with relative preservation of non-declarative memory. Cholinesterase inhibitors has been purported to enhance cognitive function, and previous clinical trials consiste Read More

Executive functions describe a variety of cognitive processes responsible for structuring behaviors around goals, and developing plans to achieve those goals in relation to the environment. In addition to deficits in basal forebrain cholinergic neuronal input into the frontal cortex, impaired control of executive function has been associated with lesions to the frontal cortex and its basal ganglia-thalamic connections. In additio Read More

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Transgenic mouse models of Alzheimer's disease (AD) are being utilized as models for elucidating AD etiology and potential therapeutic approaches. However, two major drawbacks of these models are: (1) transgenic animals often over-express amyloid beta (Aβ) to high levels compared to that seen in sporadic human AD and (2) the current intellectual property issues surrounding a number of these models ma Read More

Amyloid peptides (Aβ) are fragments of the Amyloid Precursor Protein (APP), an integral membrane protein. Aβ peptides are continuously generated by neurons and non-neuronal cells via sequential cleavage of APP by secretases. In particular, Aβ1-42 is the main component of the senile plaques associated with Alzheimer's disease (AD). Glial cells participate in the uptake of soluble extra-cellular Aβ and in the cleara Read More

The aggregation of tau protein into paired helical filaments is one of the hallmarks of Alzheimer's disease and related dementias. We therefore continue our search for non-toxic, cell penetrating inhibitors of tau aggregation, which hold potential for brain penetration. Pickhardt et al. (2005) have reported a high throughput screen for tau aggregation inhibitors previously, which resulted in the identification of several hit classe Read More

CATIE-AD was a multicenter effectiveness trial of atypical antipsychotics in patients with agitation and psychosis associated with AD who resided in the community. The study enrolled 421 participants. In this paper we present and discuss baseline characteristics of participants (demographics, cognitive, behavioral, and functional assessments), caregivers (demographics and caregiver burden) and settings at randomization. Tho Read More