Detection of Niemann-Pick disease comprising detection of lysozyme and cathepsins

Provided herein are methods for detecting an increased probability or risk of neurodegeneration in a subject. In some embodiments the method comprises assaying a sample from the subject for lysozyme and/or cathepsin S and detecting the lysozyme and/or cathepsin S from the sample, wherein an increased lysozyme and/or cathepsin S compared to levels in a control subject sample indicate an increased probability or risk of neurodegeneration. Methods of treatment and screening assays for determining drug effectiveness are also provided herein.