texas-red and Alzheimer-Disease

In this chapter we describe in detail the surgical and imaging techniques employed for the study of the anatomical routes of drainage of cerebrospinal fluid (CSF) and interstitial fluid (ISF) from the brain. The types of tracers, sites of injection, and volumes injected are crucial. For example, when testing the drainage of ISF from the parenchyma, volumes larger than 0.5 μL result in spillage of ISF into the ventricular CSF.

Topics: Alzheimer Disease; Animals; Cisterna Magna; Extracellular Fluid; Fixatives; Fluorescent Dyes; Formaldehyde; Hippocampus; Humans; Immunohistochemistry; Injections, Intraventricular; Lymphatic Vessels; Mice; Microscopy, Fluorescence; Parenchymal Tissue; Perfusion; Polymers; Stereotaxic Techniques; Tissue Embedding; Xanthenes

Antibodies to different phosphorylated and non-phosphorylated tau epitopes have been used to identify three histologically distinct types of neurofibrillary tangles in Alzheimer's disease. Intracellular tangles (Type 1) were identified by antibodies recognizing epitopes throughout the tau molecule, including the NH2-terminus. Compact extracellular tangles (Type 2) were characterized by the loss of NH2-terminal immunoreactivity and retention of other tau epitopes. Dispersed extracellular tangles (Type 3) were characterized by the presence of epitopes associated with the microtubule binding region and the COOH-terminus. These three types of tangles, found in situ in hippocampus, could be created experimentally by proteolytic treatment of brain sections. These findings suggest that three stages of neurofibrillary degeneration can be understood as a sequential stripping of paired helical filaments in which the loss of amino-terminus epitopes, followed by loss of phosphorylated epitopes, results in the appearance of dispersed extracellular tangles containing PHF-core epitopes.

Topics: Alzheimer Disease; Antibodies; Epitopes; Fluorescein-5-isothiocyanate; Hippocampus; Humans; Immunohistochemistry; Microscopy; Nerve Degeneration; Neurofibrillary Tangles; Pronase; tau Proteins; Xanthenes