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Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer's disease and apoE TR mouse cortex.

Publication ,  Journal Article
Arold, S; Sullivan, P; Bilousova, T; Teng, E; Miller, CA; Poon, WW; Vinters, HV; Cornwell, LB; Saing, T; Cole, GM; Gylys, KH
Published in: Acta Neuropathol
January 2012

The apolipoprotein E4 allele (APOE4) contributes to Alzheimer's disease (AD) risk and APOE2 is protective, but the relevant cellular mechanisms are unknown. We have used flow cytometry analysis to measure apolipoprotein E (apoE) and amyloid beta peptide (Aβ) levels in large populations of synaptic terminals from AD and aged cognitively normal controls, and demonstrate that modest but significant increases in soluble apoE levels accompany elevated Aβ in AD cortical synapses and in an APP/PS1 rat model of AD. Dual labeling experiments document co-localization of apoE and Aβ in individual synapses with concentration of Aβ in a small population of apoE-positive synapses in both AD and controls. Consistent with a clearance role, the apoE level was higher in Aβ-positive synapses in control cases. In aged targeted replacement mice expressing human apoE, apoE2/4 synaptic terminals demonstrated the highest level of apoE and the lowest level of Aβ compared to apoE3/3 and apoE4/4 lines. In apoE2/4 terminals, the pattern of immunolabeling for apoE and Aβ closely resembled the pattern in human control cases, and elevated apoE was accompanied by elevated free cholesterol in apoE2/4 synaptic terminals. These results are consistent with a role for APOE in Aβ clearance in AD synapses, and suggest that optimal lipidation of apoE2 compared to E3 and E4 makes an important contribution to Aβ clearance and synaptic function.

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Published In

Acta Neuropathol

DOI

EISSN

1432-0533

Publication Date

January 2012

Volume

123

Issue

1

Start / End Page

39 / 52

Location

Germany

Related Subject Headings

  • Rats, Transgenic
  • Rats
  • Presynaptic Terminals
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Humans
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
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Arold, S., Sullivan, P., Bilousova, T., Teng, E., Miller, C. A., Poon, W. W., … Gylys, K. H. (2012). Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer's disease and apoE TR mouse cortex. Acta Neuropathol, 123(1), 39–52. https://doi.org/10.1007/s00401-011-0892-1
Arold, Stephen, Patrick Sullivan, Tina Bilousova, Edmond Teng, Carol A. Miller, Wayne W. Poon, Harry V. Vinters, et al. “Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer's disease and apoE TR mouse cortex.Acta Neuropathol 123, no. 1 (January 2012): 39–52. https://doi.org/10.1007/s00401-011-0892-1.
Arold S, Sullivan P, Bilousova T, Teng E, Miller CA, Poon WW, et al. Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer's disease and apoE TR mouse cortex. Acta Neuropathol. 2012 Jan;123(1):39–52.
Arold, Stephen, et al. “Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer's disease and apoE TR mouse cortex.Acta Neuropathol, vol. 123, no. 1, Jan. 2012, pp. 39–52. Pubmed, doi:10.1007/s00401-011-0892-1.
Arold S, Sullivan P, Bilousova T, Teng E, Miller CA, Poon WW, Vinters HV, Cornwell LB, Saing T, Cole GM, Gylys KH. Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer's disease and apoE TR mouse cortex. Acta Neuropathol. 2012 Jan;123(1):39–52.
Journal cover image

Published In

Acta Neuropathol

DOI

EISSN

1432-0533

Publication Date

January 2012

Volume

123

Issue

1

Start / End Page

39 / 52

Location

Germany

Related Subject Headings

  • Rats, Transgenic
  • Rats
  • Presynaptic Terminals
  • Neurology & Neurosurgery
  • Mice, Transgenic
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Humans
  • Female