Neurobiologist Ryan Watts and his colleagues at the biotechnology company Genentech in South San Francisco have sought to break through the barrier by exploiting transferrin, a protein that sits on the surface of blood vessels and carries iron into the brain. The team created an antibody with two ends. One end binds loosely to transferrin and uses the protein to transport itself into the brain. And once the antibody is inside, its other end targets an enzyme called β-secretase 1 (BACE1), which produces amyloid-β. Crucially, the antibody binds more tightly to BACE1 than to transferrin, and this pulls it off the blood vessel and into the brain. It locks BACE1 shut and prevents it from making amyloid-β.
http://www.nature.com/news/alzheimer-s-drug-sneaks-through-blood-brain-barrier-1.16291
Showing posts with label alzheimer's. Show all posts
Showing posts with label alzheimer's. Show all posts
Monday, November 10, 2014
Thursday, July 17, 2014
Plasma proteins predict conversion to dementia from prodromal disease
http://www.sciencedirect.com/science/article/pii/S1552526014024546
Abstract
Background
The study aimed to validate previously discovered plasma biomarkers associated with AD, using a design based on imaging measures as surrogate for disease severity and assess their prognostic value in predicting conversion to dementia.
Methods
Three multicenter cohorts of cognitively healthy elderly, mild cognitive impairment (MCI), and AD participants with standardized clinical assessments and structural neuroimaging measures were used. Twenty-six candidate proteins were quantified in 1148 subjects using multiplex (xMAP) assays.
Results
Sixteen proteins correlated with disease severity and cognitive decline. Strongest associations were in the MCI group with a panel of 10 proteins predicting progression to AD (accuracy 87%, sensitivity 85%, and specificity 88%).
Conclusions
We have identified 10 plasma proteins strongly associated with disease severity and disease progression. Such markers may be useful for patient selection for clinical trials and assessment of patients with predisease subjective memory complaints.
Keywords
Plasma; Mild cognitive impairment; Pathology; Alzheimer's disease; Biomarker; Prediction and magnetic resonance imaging
Abstract
Background
The study aimed to validate previously discovered plasma biomarkers associated with AD, using a design based on imaging measures as surrogate for disease severity and assess their prognostic value in predicting conversion to dementia.
Methods
Three multicenter cohorts of cognitively healthy elderly, mild cognitive impairment (MCI), and AD participants with standardized clinical assessments and structural neuroimaging measures were used. Twenty-six candidate proteins were quantified in 1148 subjects using multiplex (xMAP) assays.
Results
Sixteen proteins correlated with disease severity and cognitive decline. Strongest associations were in the MCI group with a panel of 10 proteins predicting progression to AD (accuracy 87%, sensitivity 85%, and specificity 88%).
Conclusions
We have identified 10 plasma proteins strongly associated with disease severity and disease progression. Such markers may be useful for patient selection for clinical trials and assessment of patients with predisease subjective memory complaints.
Keywords
Plasma; Mild cognitive impairment; Pathology; Alzheimer's disease; Biomarker; Prediction and magnetic resonance imaging
Thursday, July 5, 2012
Alzheimer's disease: A breach in the blood–brain barrier
http://www.nature.com/nature/journal/v485/n7399/full/485451a.html
Bell et al. find that APOE3 — which does not trigger BBB dysfunction — binds to a receptor protein (LRP1) on the surface of pericytes and, by doing so, prevents the inflammatory response. By contrast, in mice expressing APOE4 or lacking any APOE proteins, this interaction does not occur, and the resulting inflammatory response breaks down the BBB. The authors' findings suggest that APOE4 cannot bind to LRP1 as efficiently as does APOE3, and so fails to 'cool down' the brain pericytes. Of note, the researchers show that the APOE4-triggered changes in the BBB precede neurological deterioration in the mice studied. Moreover, chemical inhibitors of this pro-inflammatory pathway healed the breached BBB and ameliorated the neuronal changes in the animals, opening up the possibility of improved treatment of Alzheimer's disease.
Apolipoprotein E controls cerebrovascular integrity via cyclophilin A (Bell et al. 2012)
http://www.ncbi.nlm.nih.gov/
Bell et al. find that APOE3 — which does not trigger BBB dysfunction — binds to a receptor protein (LRP1) on the surface of pericytes and, by doing so, prevents the inflammatory response. By contrast, in mice expressing APOE4 or lacking any APOE proteins, this interaction does not occur, and the resulting inflammatory response breaks down the BBB. The authors' findings suggest that APOE4 cannot bind to LRP1 as efficiently as does APOE3, and so fails to 'cool down' the brain pericytes. Of note, the researchers show that the APOE4-triggered changes in the BBB precede neurological deterioration in the mice studied. Moreover, chemical inhibitors of this pro-inflammatory pathway healed the breached BBB and ameliorated the neuronal changes in the animals, opening up the possibility of improved treatment of Alzheimer's disease.
Apolipoprotein E controls cerebrovascular integrity via cyclophilin A (Bell et al. 2012)
http://www.ncbi.nlm.nih.gov/
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