The present invention relates to the field of Alzheimer's disease (AD). More specifically, the present invention provides methods and compositions useful in diagnosing and assessing AD. In another embodiment, a method for diagnosing Alzheimer's Disease (AD) in a patient comprises the steps of (a) obtaining CSF sample from the patient; (b) adding to the sample isotopically labeled peptides identical to a portion of one or more biomarker proteins, wherein the one or more biomarker proteins comprise total APP, APP isoform 751, APP isoform 770, amyloid beta 40 peptide, APOE, and Clusterin; and (c) measuring the one or more biomarker proteins in the sample using mass spectrometry, wherein the level of one or more biomarker proteins compared to a control correlates with AD in the patient.