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Alzheimer's disease (AD) pathology is estimated to develop many years before detectable cognitive decline. Fluid and imaging biomarkers may identify people in early symptomatic and even preclinical stages, possibly when potential treatments can best preserve cognitive function. We previously reported that cerebrospinal fluid (CSF) levels of amyloid-beta(42)(More)
OBJECTIVE For therapies for Alzheimer's disease (AD) to have the greatest impact, it will likely be necessary to treat individuals in the "preclinical" (presymptomatic) stage. Fluid and neuroimaging measures are being explored as possible biomarkers of AD pathology that could aid in identifying individuals in this stage to target them for clinical trials(More)
OBJECTIVES Amyloid-beta(42) (Abeta(42)) appears central to Alzheimer's disease (AD) pathogenesis and is a major component of amyloid plaques. Mean cerebrospinal fluid (CSF) Abeta(42) is decreased in dementia of the Alzheimer's type. This decrease may reflect plaques acting as an Abeta(42) "sink," hindering transport of soluble Abeta(42) between brain and(More)
Hypoxic-ischemic (H-I) brain injury in the human perinatal period often leads to significant long-term neurobehavioral dysfunction in the cognitive and sensory-motor domains. Using a neonatal H-I injury model (unilateral carotid ligation followed by hypoxia) in postnatal day seven rats, previous studies have shown that neurotrophins, such as brain-derived(More)
BACKGROUND We have previously characterised functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's disease. To gain further knowledge on the preclinical phase of Alzheimer's disease, we sought to characterise structural and functional MRI, CSF, and plasma biomarkers in a cohort of young adults carrying a high-penetrance(More)
Hypoxic-ischemic (H-I) injury to the brain in the perinatal period often leads to significant long-term neurological deficits. In a model of neonatal H-I injury in postnatal day 7 rats, our previous data have shown that cell death with features of apoptosis is prominent between 6 and 24 h after H-I and that neurotrophins, particularly BDNF, can markedly(More)
BACKGROUND HIV-associated neurologic disorders (HAND) continue to develop in many patients with HIV. CSF amyloid measurements in HAND have been reported to be similar to those in dementia of the Alzheimer type (DAT). Confirmatory evaluation of this finding in carefully evaluated subjects is needed. METHODS CSF specimens were obtained from subjects(More)
Cerebral ischemia is often followed by a period of delayed hypoperfusion that may contribute to tissue injury. We tested the hypothesis that augmentation of interstitial adenosine can improve tissue perfusion under this condition 10 min global ischemia was produced in two groups of isoflurane-anesthetized newborn pigs by occlusion of subclavian and(More)
OBJECTIVE Biomarkers are needed to improve the sensitivity and accuracy of diagnosis, and also prognosis, in individuals with early Alzheimer disease (AD). Measures of brain structure and disease-related proteins in the cerebrospinal fluid (CSF) have been proposed as biomarkers, yet relatively little is known about the relationships between such measures.(More)
Very recent studies in adult gerbils and rats have shown that exposure to sublethal ischemia can confer neuroprotection from subsequent lethal ischemic episodes. To determine if a similar phenomenon can be elicited during the perinatal period, we have developed a preconditioning regimen that involves exposure to normothermic hypoxia (8% oxygen) 24 h prior(More)