Lary C. Walker

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Protein aggregation is an established pathogenic mechanism in Alzheimer's disease, but little is known about the initiation of this process in vivo. Intracerebral injection of dilute, amyloid-beta (Abeta)-containing brain extracts from humans with Alzheimer's disease or beta-amyloid precursor protein (APP) transgenic mice induced cerebral beta-amyloidosis(More)
For several decades scientists have speculated that the key to understanding age-related neurodegenerative disorders may be found in the unusual biology of the prion diseases. Recently, owing largely to the advent of new disease models, this hypothesis has gained experimental momentum. In a remarkable variety of diseases, specific proteins have been found(More)
The misfolding and aggregation of specific proteins is a seminal occurrence in a remarkable variety of neurodegenerative disorders. In Alzheimer disease (the most prevalent cerebral proteopathy), the two principal aggregating proteins are β-amyloid (Aβ) and tau. The abnormal assemblies formed by conformational variants of these proteins range in size from(More)
The intracerebral injection of β-amyloid-containing brain extracts can induce cerebral β-amyloidosis and associated pathologies in susceptible hosts. We found that intraperitoneal inoculation with β-amyloid-rich extracts induced β-amyloidosis in the brains of β-amyloid precursor protein transgenic mice after prolonged incubation times.
Many neurodegenerative diseases are associated with the abnormal sequestration of disease-specific proteins in the brain, but the events that initiate this process remain unclear. To determine whether the deposition of the beta-amyloid peptide (Abeta), a key pathological feature of Alzheimer's disease (AD), can be induced in vivo, we infused dilute(More)
Following cerebral ischemia, perilesional astrocytes and activated microglia form a glial scar that hinders the genesis of new axons and blood vessels in the infarcted region. Since glial reactivity is chronically augmented in the normal aging brain, the authors hypothesized that postischemic gliosis would be temporally abnormal in aged rats compared to(More)
Ultrastructural reconstruction of 27 fibrillar plaques in different stages of formation and maturation was undertaken to characterize the development of fibrillar plaques in the brains of human APP(SW) transgenic mice (Tg2576). The study suggests that microglial cells are not engaged in Abeta removal and plaque degradation, but in contrast, are a driving(More)
To determine whether the decline of behavioral abilities with aging in monkeys is selective or widespread, we examined 18 monkeys ranging from 3 to 34 years of age on a wide variety of tests with the ultimate goal of correlating behavioral deficits with age-related changes in the brain. In our initial study we found impaired visual recognition ability in(More)
The age-related decline in plasticity of the brain may be one factor underlying poor functional recovery after stroke. In the present work we tested the hypothesis that the attenuation of neural plasticity in old age could be the result of an altered temporal relationship between factors promoting brain plasticity [microtubule-associated protein 1B (MAP1B)](More)
Transgenic mice (Tg2576) overexpressing human beta-amyloid precursor protein with the Swedish mutation (APP695SWE) develop Alzheimer's disease-like amyloid beta protein (Abeta) deposits by 8 to 10 months of age. These mice show elevated levels of Abeta40 and Abeta42, as well as an age-related increase in diffuse and compact senile plaques in the brain.(More)