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N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits.
Acta Neuropathol 2013; 126(2):189-205AN

Abstract

N-truncated Aβ4-42 is highly abundant in Alzheimer disease (AD) brain and was the first Aβ peptide discovered in AD plaques. However, a possible role in AD aetiology has largely been neglected. In the present report, we demonstrate that Aβ4-42 rapidly forms aggregates possessing a high aggregation propensity in terms of monomer consumption and oligomer formation. Short-term treatment of primary cortical neurons indicated that Aβ4-42 is as toxic as pyroglutamate Aβ3-42 and Aβ1-42. In line with these findings, treatment of wildtype mice using intraventricular Aβ injection induced significant working memory deficits with Aβ4-42, pyroglutamate Aβ3-42 and Aβ1-42. Transgenic mice expressing Aβ4-42 (Tg4-42 transgenic line) developed a massive CA1 pyramidal neuron loss in the hippocampus. The hippocampus-specific expression of Aβ4-42 correlates well with age-dependent spatial reference memory deficits assessed by the Morris water maze test. Our findings indicate that N-truncated Aβ4-42 triggers acute and long-lasting behavioral deficits comparable to AD typical memory dysfunction.

Authors+Show Affiliations

Division of Molecular Psychiatry, Georg-August-University Goettingen, University Medicine Goettingen, von-Siebold-Strasse 5, 37075, Goettingen, Germany.No 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 availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23685882

Citation

Bouter, Yvonne, et al. "N-truncated Amyloid Β (Aβ) 4-42 Forms Stable Aggregates and Induces Acute and Long-lasting Behavioral Deficits." Acta Neuropathologica, vol. 126, no. 2, 2013, pp. 189-205.
Bouter Y, Dietrich K, Wittnam JL, et al. N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits. Acta Neuropathol. 2013;126(2):189-205.
Bouter, Y., Dietrich, K., Wittnam, J. L., Rezaei-Ghaleh, N., Pillot, T., Papot-Couturier, S., ... Bayer, T. A. (2013). N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits. Acta Neuropathologica, 126(2), pp. 189-205. doi:10.1007/s00401-013-1129-2.
Bouter Y, et al. N-truncated Amyloid Β (Aβ) 4-42 Forms Stable Aggregates and Induces Acute and Long-lasting Behavioral Deficits. Acta Neuropathol. 2013;126(2):189-205. PubMed PMID: 23685882.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - N-truncated amyloid β (Aβ) 4-42 forms stable aggregates and induces acute and long-lasting behavioral deficits. AU - Bouter,Yvonne, AU - Dietrich,Katharina, AU - Wittnam,Jessica L, AU - Rezaei-Ghaleh,Nasrollah, AU - Pillot,Thierry, AU - Papot-Couturier,Sophie, AU - Lefebvre,Thomas, AU - Sprenger,Frederick, AU - Wirths,Oliver, AU - Zweckstetter,Markus, AU - Bayer,Thomas A, Y1 - 2013/05/18/ PY - 2013/03/05/received PY - 2013/05/09/accepted PY - 2013/05/08/revised PY - 2013/5/21/entrez PY - 2013/5/21/pubmed PY - 2013/10/23/medline SP - 189 EP - 205 JF - Acta neuropathologica JO - Acta Neuropathol. VL - 126 IS - 2 N2 - N-truncated Aβ4-42 is highly abundant in Alzheimer disease (AD) brain and was the first Aβ peptide discovered in AD plaques. However, a possible role in AD aetiology has largely been neglected. In the present report, we demonstrate that Aβ4-42 rapidly forms aggregates possessing a high aggregation propensity in terms of monomer consumption and oligomer formation. Short-term treatment of primary cortical neurons indicated that Aβ4-42 is as toxic as pyroglutamate Aβ3-42 and Aβ1-42. In line with these findings, treatment of wildtype mice using intraventricular Aβ injection induced significant working memory deficits with Aβ4-42, pyroglutamate Aβ3-42 and Aβ1-42. Transgenic mice expressing Aβ4-42 (Tg4-42 transgenic line) developed a massive CA1 pyramidal neuron loss in the hippocampus. The hippocampus-specific expression of Aβ4-42 correlates well with age-dependent spatial reference memory deficits assessed by the Morris water maze test. Our findings indicate that N-truncated Aβ4-42 triggers acute and long-lasting behavioral deficits comparable to AD typical memory dysfunction. SN - 1432-0533 UR - https://www.unboundmedicine.com/medline/citation/23685882/N_truncated_amyloid_β__Aβ__4_42_forms_stable_aggregates_and_induces_acute_and_long_lasting_behavioral_deficits_ L2 - https://dx.doi.org/10.1007/s00401-013-1129-2 DB - PRIME DP - Unbound Medicine ER -