Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

Apolipoprotein E associates with beta amyloid peptide of Alzheimer's disease to form novel monofibrils. Isoform apoE4 associates more efficiently than apoE3.

D A Sanan; K H Weisgraber; S J Russell; R W Mahley; D Huang; A Saunders; D Schmechel; T Wisniewski; B Frangione; A D Roses (Profiled Authors: Roses, Allen D; Schmechel, Donald E; Saunders, Ann M; Frangione, Blas)

Gladstone Institute of Cardiovascular Disease, Cardiovascular Research Institute, San Francisco, California 94141-9100.
The Journal of clinical investigation 1994;94(2):860-9.

Late-onset and sporadic Alzheimer's disease are associated with the apolipoprotein E (apoE) type 4 allele expressing the protein isoform apoE4. Apolipoprotein E binds avidly to beta amyloid (A beta) peptide, a major component of senile plaque of Alzheimer's disease, in an isoform-specific manner. The apoE4 isoform binds to A beta peptide more rapidly than apoE3. We observed that soluble SDS-stable complexes of apoE3 or apoE4, formed by coincubation with A beta peptide, precipitated after several days of incubation at 37 degrees C with apoE4 complexes precipitating more rapidly than apoE3 complexes. A beta(1-28) and A beta(1-40) peptides were incubated in the presence or absence of apoE3, apoE4, or bovine serum albumin for 4 d at 37 degrees C (pH 7.3). Negative stain electron microscopy revealed that the A beta peptide alone self-assembled into twisted ribbons containing two or three strands but occasionally into multistranded sheets. The apoE/A beta coincubates yielded monofibrils 7 nm in diameter. ApoE4/A beta coincubates yielded a denser matrix of monofibrils than apoE3/A beta coincubates. Unlike purely monofibrillar apoE4/A beta coincubates, apoE3/A beta coincubates also contained double- and triple-stranded structures. Both apoE isoforms were shown by immunogold labeling to be uniformly distributed along the A beta peptide monofibrils. Monofibrils appeared earlier in apoE4/A beta than in apoE3/A beta in time-course experiments. Thus apoE3 and apoE4 each interact with beta amyloid peptide to form novel monofibrillar structures, apoE4 more avidly, a finding consistent with the biochemical and genetic association between apoE4 and Alzheimer's disease.

4 Originating Grant

• 1.

  Schmechel, Donald E

  ALZHEIMER'S DISEASE RESEARCH CENTER

  1 May 2000 - 30 April 2005

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 16,537,307

• 2.

  ROSES, ALLEN D

  GENETICS OF LATE AND EARLY ONSET ALZHEIMERS DISEASE

  1 August 1988 - 31 July 1996

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 5,327,551

• 3.

  ROSES, ALLEN D

  ALZHEIMERS DISEASE RESEARCH CENTER

  30 September 1985 - 30 April 2000

  NATIONAL INSTITUTE ON AGING

  Total Funding: $ 17,660,528

• 4.

  Frangione, Blas

  ALZHEIMERS DISEASE AND AMYLOID PROTEINS

  Total Funding: $ 4,881,560

Scientific Context

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