early brain dysfunction that could be assessed as an outcome measure in response to therapeutic interventions. very mildly impaired humans who are developing AD pathology, the sleep-wake cycle may be a useful indicator of accumulation. If analogous abnormalities in the sleep-wake cycle are present in cognitively normal and β caused by A fluctuation and normal sleep patterns. These findings sugg...

β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) initiates the production of β-amyloid (Aβ), the major constituent of amyloid plaques in Alzheimer's disease (AD). BACE1 is elevated ∼2-3 fold in AD brain and is concentrated in dystrophic neurites near plaques, suggesting BACE1 elevation is Aβ-dependent. Previously, we showed that phosphorylation of the translation initiation fact...

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that involves strong inflammatory components. Aberrant and prolonged inflammation in the CNS thought to contribute development of pathology. The use single cytokine approaches curb or leverage mechanisms for modifying benefit has often resulted conflicting data. Furthermore, these treatments were usually delivered locally into par...

One of the neuropathological hallmarks of Alzheimer's disease (AD) is the amyloid plaque, primarily composed of aggregated amyloid-beta (Abeta) peptide. In vitro, Abeta(1-42), the major alloform of Abeta found in plaques, self-assembles into fibrils at micromolar concentrations and acidic pH. Such conditions do not exist in the extracellular fluid of the brain where the pH is neutral and Abeta ...

BACKGROUND Most Alzheimer's disease (AD) cases arise sporadically and may involve innate immune activation of microglial expressed Toll-like receptors regulated through the myeloid differentiation protein 88 (MyD88) pathway. OBJECTIVE It was the aim of this study to test the innate immune involvement in AD pathology. METHODS We mated APPsw/PS1ΔE9 mice with MyD88-deficient mice. RESULTS Pr...

Brain positron emission tomography (PET) has also been used over many years to diagnose neurodegenerative diseases, and has advantages over MRI due to its higher sensitivity to detect pathologies at a molecular level. While 18F-fluorodeoxyglucose (FDG) PETCT is an established imaging technique for assisting in the differential diagnosis of Alzheimer’s disease (AD) and other forms of dementia, P...

Prominent cerebral amyloid angiopathy is often observed in the brains of elderly individuals and is almost universally found in patients with Alzheimer's disease. Cerebral amyloid angiopathy is characterized by accumulation of the shorter amyloid-β isoform(s) (predominantly amyloid-β40) in the walls of leptomeningeal and cortical arterioles and is likely a contributory factor to vascular dysfun...

Despite many years of intensive study, the specific amyloid-b species in the human brain responsible for the pathophysiological processes underlying Alzheimer’s disease have yet to be identified. In part, this may be because we have been ‘searching under the streetlight’: examination of other sources of amyloid-b such as synthetic preparations, material derived from the brains of transgenic ani...

BACKGROUND NADPH oxidase is implicated in neurotoxic microglial activation and the progressive nature of Alzheimer's Disease (AD). Here, we test the ability of two NADPH oxidase inhibitors, apocynin and dextromethorphan (DM), to reduce learning deficits and neuropathology in transgenic mice overexpressing human amyloid precursor protein with the Swedish and London mutations (hAPP(751)(SL)). M...