Positron Emission Tomography (PET) is widely used for cancer screening, heart disease, brain disease, and etc. Alzheimer’s disease, known as the most common form of dementia, has several competing hypotheses to explain the cause of the disease. The amyloid hypothesis postulated that the major reason of Alzheimer’s disease is due to precipitation of extracellular amyloid beta (Aβ) . This disease can be diagnosed by measuring the distribution of beta amyloid plaques using PET. PET for the whole body has the advantage of being able to inspect large objects, but it is expensive and has a low sensitivity. Optimized brain PET for diagnosis of Alzheimer’s disease is needed. The purpose of this study is to design of brain PET with depth of interaction (DOI) for diagnosis of Alzheimer’s disease using Monte Carlo simulation. If the length of the scintillation crystal is long, a parallax error occurs in which two gamma rays generated at a distance from the origin are obliquely incident on the scintillation crystal. This error makes the spatial resolution non-uniform and can be corrected by measuring DOI. The spatial resolution of brain PET should be uniform because beta amyloid plaques are more distributed in the outside than in the center of the brain. Many DOI measurement techniques have been developed. DOI techniques, based on sharing and redirection of scintillation light among multiple detectors and together with attenuation of light over the length of the crystals were used for this study . Figure 1 shows DOI techniques. The overall dimensions of LYSO were 24 x 24 x 15 mm3, each 3 x 3 x 15 mm3, and each lateral faces were depolished for DOI. The Geant4 Application for Tomographic Emission: a simulation toolkit for PET and SPECT was used this study to design of brain PET. Brain PET consisted of detector module, ring detector, signal processing board, data acquisition board, reconstruction algorithm, and software. Detector module and ring detector consisted of two sets of 8x8 array LYSO coupled silicon photomultiplier and 72 modules, respectively. The inner diameter and axial length of brain PET were 293.5 mm and 51 mm, respectively. Radioactive source emitting 511 keV gamma rays was located at the center and outside of detector ring. Uniformity of spatial resolution, energy resolution, and sensitivity will be evaluated.