Journal of Molecular Neuroscience

, Volume 23, Issue 3, pp 189–204 | Cite as

Apolipoprotein E

Diversity of cellular origins, structural and biophysical properties, and effects in Alzheimer’s disease
  • Yadong Huang
  • Karl H. Weisgraber
  • Lennart Mucke
  • Robert W. Mahley
Original Article


Apolipoprotein E4 (apoE4) is a major risk factor for Alzheimer’s disease (AD). Several hypotheses have been proposed to explain the association of the APOE ε4 allele with AD; however, the mechanisms underlying this association are largely unknown. Initially, apoE was thought to be synthesized primarily by astrocytes but not by neurons in the brain. However, subsequent studies have demonstrated that central nervous system neurons also express apoE under diverse physiological and pathological conditions. Detailed studies of the structure and biophysical properties of apoE isoforms have demonstrated unique properties distinguishing apoE4 from apoE3. Because the structural and biophysical properties of a protein determine how it functions under normal and abnormal conditions, apoE4, with its multiple cellular origins and multiple structural and biophysical properties, might contribute to the pathology of AD through several different mechanisms. Some of these mechanisms might be suitable targets for the development of new treatments for AD.

Index Entries

Alzheimer’s disease apolipoprotein E proteolysis therapeutics transgenic mice 


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Copyright information

© Humana Press Inc 2004

Authors and Affiliations

  • Yadong Huang
    • 1
    • 2
    • 3
  • Karl H. Weisgraber
    • 1
    • 2
    • 3
  • Lennart Mucke
    • 1
    • 4
  • Robert W. Mahley
    • 1
    • 2
    • 3
    • 5
  1. 1.Gladstone Institute of Neurological DiseaseUniversity of CaliforniaSan Francisco
  2. 2.Gladstone Institute of Cardiovascular DiseaseUniversity of CaliforniaSan Francisco
  3. 3.Department of PathologyUniversity of CaliforniaSan Francisco
  4. 4.Department of NeurologyUniversity of CaliforniaSan Francisco
  5. 5.Department of MedicineUniversity of CaliforniaSan Francisco

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