Endogenous murine A beta increases amyloid deposition in APP23 but not in APPPS1 transgenic mice
2015 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 36, no 7, 2241-2247 p.Article in journal (Refereed) Published
Endogenous murine amyloid-beta peptide (A beta) is expressed in most A beta precursor protein (APP) transgenic mouse models of Alzheimers disease but its contribution to beta-amyloidosis remains unclear. We demonstrate similar to 35% increased cerebral A beta load in APP23 transgenic mice compared with age-matched APP23 mice on an App-null background. No such difference was found for the much faster A beta-depositing APPPS1 transgenic mouse model between animals with or without the murine App gene. Nevertheless, both APP23 and APPPS1 mice codeposited murine A beta, and immunoelectron microscopy revealed a tight association of murine A beta with human A beta fibrils. Deposition of murine A beta was considerably less efficient compared with the deposition of human A beta indicating a lower amyloidogenic potential of murine A beta in vivo. The amyloid dyes Pittsburgh Compound-B and pentamer formyl thiophene acetic acid did not differentiate between amyloid deposits consisting of human A beta and deposits of mixed human-murine A beta. Our data demonstrate a differential effect of murine A beta on human A beta deposition in different APP transgenic mice. The mechanistically complex interaction of human and mouse A beta may affect pathogenesis of the models and should be considered when models are used for translational preclinical studies.
Place, publisher, year, edition, pages
Elsevier , 2015. Vol. 36, no 7, 2241-2247 p.
Alzheimers disease; APP transgenic mouse models; Murine APP knockout; Murine amyloid-beta (A beta); Beta-amyloid; Mixed amyloid-beta (A beta) fibrils
IdentifiersURN: urn:nbn:se:liu:diva-119786DOI: 10.1016/j.neurobiolaging.2015.03.011ISI: 000355378700003PubMedID: 25911278OAI: oai:DiVA.org:liu-119786DiVA: diva2:827279
Funding Agencies|German Network in Degenerative Dementias [BMBF-01G10705]; NIA [AG017617]; Hertie Foundation, Frankfurt, Germany; ERC Starting Independent Researcher Grant (Project: MUMID) from the European Research Council2015-06-262015-06-262015-06-26