Choroidal lesions preceding symptom onset in birdshot chorioretinopathy.
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Adult↗
Biomedical subjects
Alex Harper
Publications and source records attributed to Alex Harper.
Elevated levels of amyloid precursor protein in muscle of patients with amyotrophic lateral sclerosis and a mouse model of the disease.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease defined by motor neuron loss. Transgenic mouse models show features that closely mimic those seen in the clinical situation, reflected in the molecular changes observed in mouse models and in tissues from patients. We report a dramatic increase in the expression of amyloid precursor protein (APP) in the hindlimb muscles, but not the spinal cord of the G93A transgenic mouse model, significantly before the appearance of clinical abnormalities. APP levels were unchanged in nontransgenic mice and in mice overexpressing human wild-type Cu/Zn-dependent superoxide dismutase 1 (SOD1). Preliminary results indicate a similar change in APP expression in human deltoid muscle samples from ALS patients compared with age-matched controls. The inhibitory role of APP in innervation at the neuromuscular junction and increased expression in inclusion-body myositis suggest that presymptomatic upregulation of APP may be consistent with a potential role for APP in ALS pathology.
Adult↗
Imaging and spatial distribution of beta-amyloid peptide and metal ions in Alzheimer's plaques by laser ablation-inductively coupled plasma-mass spectrometry.
Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) has been developed as a new strategy for detection and imaging of beta-amyloid protein in immunohistochemical sections from the brains of a transgenic mouse model of Alzheimer's disease. The distribution of beta-amyloid deposits in tissue was based on measurement of Eu- and Ni-coupled antibodies. The laser-based methodologies (spot ablation, single line raster, and two-dimensional imaging) were also used to detect and map trace element distributions and thus provide a novel probe for both elemental and protein data. We also report the combination of laser capture microdissection with LA-ICP-MS as an alternative strategy for microanalysis of immunohistochemical sections.
Alzheimer Disease↗