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Endogenous murine A? increases amyloid deposition in APP23 but not in APPPS1 transgenic mice.


ABSTRACT: Endogenous murine amyloid-? peptide (A?) is expressed in most A? precursor protein (APP) transgenic mouse models of Alzheimer's disease but its contribution to ?-amyloidosis remains unclear. We demonstrate ? 35% increased cerebral A? 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?-depositing APPPS1 transgenic mouse model between animals with or without the murine App gene. Nevertheless, both APP23 and APPPS1 mice codeposited murine A?, and immunoelectron microscopy revealed a tight association of murine A? with human A? fibrils. Deposition of murine A? was considerably less efficient compared with the deposition of human A? indicating a lower amyloidogenic potential of murine A? in vivo. The amyloid dyes Pittsburgh Compound-B and pentamer formyl thiophene acetic acid did not differentiate between amyloid deposits consisting of human A? and deposits of mixed human-murine A?. Our data demonstrate a differential effect of murine A? on human A? deposition in different APP transgenic mice. The mechanistically complex interaction of human and mouse A? may affect pathogenesis of the models and should be considered when models are used for translational preclinical studies.

SUBMITTER: Mahler J 

PROVIDER: S-EPMC4457564 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Endogenous murine amyloid-β peptide (Aβ) is expressed in most Aβ precursor protein (APP) transgenic mouse models of Alzheimer's disease but its contribution to β-amyloidosis remains unclear. We demonstrate ∼ 35% increased cerebral Aβ 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 Aβ-depositing APPPS1 transgenic mouse model between animals with or without the murine App gene. Nevertheless, both APP23 a  ...[more]

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