Objective: Study on the value of the corpus callosum measurement at mid-sagittal slice of magnetic resonance imaging (MRI) and the phosphorylated tau protein (p-tau) and Amyloid beta (Abeta) 1-42 immunoreactive deposits (Aβ 1-42) assay in cerebral spinal fluid (CSF) on early Alzheimer's disease (AD) diagnosis. Methods: Consecutive probable AD diagnosed with the National institute of neurology and communication disorder and stroke-Alzheimer disease or AD related disease academy (NINCDS-ADRDA) criteria were divided into two groups according to MMSE score. The average MMSE score were 20.5 ± 2.5 in group AD1 and 14.7 ± 3.8 in Group AD2, and was 27.8 ± 1.7 in control group, which was well matched with the two AD groups in gender, age and education degree. The area of corpus callosum was measured directly by the autmeas soft ware on MRI, and the levels of p-tau and Aβ 1-42 in CSF were assaied by enzyme-labeled immunosorbent assay (ELISA). Results: The levels of p-tau in CSF in AD1 group was (25.8 ± 3.1) pg/ml, which was higher than that of sex-and age-matched normal control (17.7 ± 1.5) pg/ml, and the level of Aβ 1-42 in AD1 group was (329.3 ± 15.2) pg/ml, which was lower than that of normal control (522.5 ± 15.1) pg/ml. AD1 group has a mild corpus callosum shrink. There was a remarkably corpus callosum shrinke in AD2 group, especially at the area of the head and body of callus. The level of p-tau increased and the level of Aβ 1-42 decreased remarkably in AD2 group (31.3 ± 4.8) pg/ml and (318.5 ± 30.8) pg/ml than that in AD1 group. Conclusions: The corpus callosum measurement combined with the p-tau and Aβ 1-42 assay was useful in early AD diagnosis. Moreover, it was helpful to evaluate AD proceeding.