Apolipoprotein E (apoE) is one of the strongest risk factors of Alzheimer’s disease (AD). ApoE is known to participate in the fibril formation of amyloid β in isoform-dependent manner. Due to its amphipathic nature, apoE can possess various structural arrangements including lipidated ‘open form’ and lipid-free ‘closed form’. In this thesis, the nanoscale structures of apoE were identified using biophysical techniques such as transmission electron microscopy (TEM), synchrotron small angle X-ray scattering (SAXS), and atomic force microscopy (AFM). At high concentration (> 0.1 mg/mL), apoE existed as tetramer, which appeared as ‘short rod’ shape. Interestingly, when apoE is diluted to physiological concentration (0.01-0.05 mg/mL), it formed elongated fibril structure. This fibrillation also occurred at chemically denaturing condition and high ionic strength, suggesting that ‘open form’ of apoE can be a prerequisite of fibrillation. This finding provides new insights on apoE self-association mechanism and its role in AD pathology.