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ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42.
Neurobiol Dis 2005; 18(1):75-82ND

Abstract

Amyloid-beta1-42 (Abeta1-42) is crucial to Alzheimer disease (AD) pathogenesis but the conformation of the toxic Abeta species remains uncertain. AD risk is increased by apolipoprotein E4 (apoE4) and decreased by apoE2 compared with the apoE3 isoform, but whether inheritance of apoE4 represents a gain of negative or a loss of protective function is also unresolved. Using hippocampal slices from apoE knockout (apoE-KO) and human apoE2, E3, and E4 targeted replacement (apoE-TR) mice, we found that oligomeric Abeta1-42 inhibited long-term potentiation (LTP) with a hierarchy of susceptibility mirroring clinical AD risk (apoE4-TR > apoE3-TR = apoE-KO > apoE2-TR), and that comparable doses of unaggregated Abeta1-42 did not affect LTP. These data provide a novel link among apoE isoform, Abeta1-42, and a functional cellular model of memory. In this model, apoE4 confers a gain of negative function synergistic with Abeta1-42, apoE2 is protective, and the apoE-Abeta interaction is specific to oligomeric Abeta1-42.

Authors+Show Affiliations

Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60614, USA. btrommer@northwestern.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15649697

Citation

Trommer, Barbara L., et al. "ApoE Isoform-specific Effects On LTP: Blockade By Oligomeric Amyloid-beta1-42." Neurobiology of Disease, vol. 18, no. 1, 2005, pp. 75-82.
Trommer BL, Shah C, Yun SH, et al. ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42. Neurobiol Dis. 2005;18(1):75-82.
Trommer, B. L., Shah, C., Yun, S. H., Gamkrelidze, G., Pasternak, E. S., Stine, W. B., ... LaDu, M. J. (2005). ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42. Neurobiology of Disease, 18(1), pp. 75-82.
Trommer BL, et al. ApoE Isoform-specific Effects On LTP: Blockade By Oligomeric Amyloid-beta1-42. Neurobiol Dis. 2005;18(1):75-82. PubMed PMID: 15649697.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - ApoE isoform-specific effects on LTP: blockade by oligomeric amyloid-beta1-42. AU - Trommer,Barbara L, AU - Shah,Chirag, AU - Yun,Sung Hwan, AU - Gamkrelidze,Georgi, AU - Pasternak,Emily S, AU - Stine,W Blaine, AU - Manelli,Arlene, AU - Sullivan,Patrick, AU - Pasternak,Joseph F, AU - LaDu,Mary Jo, PY - 2004/07/28/received PY - 2004/07/28/revised PY - 2004/08/30/accepted PY - 2005/1/15/pubmed PY - 2005/5/17/medline PY - 2005/1/15/entrez SP - 75 EP - 82 JF - Neurobiology of disease JO - Neurobiol. Dis. VL - 18 IS - 1 N2 - Amyloid-beta1-42 (Abeta1-42) is crucial to Alzheimer disease (AD) pathogenesis but the conformation of the toxic Abeta species remains uncertain. AD risk is increased by apolipoprotein E4 (apoE4) and decreased by apoE2 compared with the apoE3 isoform, but whether inheritance of apoE4 represents a gain of negative or a loss of protective function is also unresolved. Using hippocampal slices from apoE knockout (apoE-KO) and human apoE2, E3, and E4 targeted replacement (apoE-TR) mice, we found that oligomeric Abeta1-42 inhibited long-term potentiation (LTP) with a hierarchy of susceptibility mirroring clinical AD risk (apoE4-TR > apoE3-TR = apoE-KO > apoE2-TR), and that comparable doses of unaggregated Abeta1-42 did not affect LTP. These data provide a novel link among apoE isoform, Abeta1-42, and a functional cellular model of memory. In this model, apoE4 confers a gain of negative function synergistic with Abeta1-42, apoE2 is protective, and the apoE-Abeta interaction is specific to oligomeric Abeta1-42. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/15649697/ApoE_isoform_specific_effects_on_LTP:_blockade_by_oligomeric_amyloid_beta1_42_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(04)00198-6 DB - PRIME DP - Unbound Medicine ER -