Intraneuronal APP and extracellular Aβ independently cause dendritic spine pathology in transgenic mouse models of Alzheimer’s disease

• DOI: 10.1007/s00401-015-1421-4
• Publication Date: 2015-04-10T19:15:00Z
• Authors: Chengyu Zou; Elena Montagna; Yuan Shi; Finn Peters; Lidia Blazquez-Ll...; Song Shi; Severin Filser; Mario M. Dorostkar; Jochen Herms
• Keywords: Amyloid (mycology); Cognitive Decline

Alzheimer’s disease (AD) is thought to be caused by accumulation of amyloid-β protein (Aβ), which a cleavage product amyloid precursor (APP). Transgenic mice overexpressing APP have been used recapitulate pathology. Among them, APP23 and APPswe/PS1deltaE9 (deltaE9) are extensively studied. express with Swedish mutation develop plaques late in their life, while cognitive deficits observed young age. In contrast, deltaE9 mutant presenilin-1 early but show typical old To unveil the reasons for different progressions decline these commonly mouse models, we analyzed number turnover dendritic spines as important structural correlates learning memory. Chronic vivo two-photon imaging apical tufts layer V pyramidal neurons revealed decreased spine density 4–5-month-old mice. age-matched mice, loss was only on cortical dendrites that were close proximity plaques. both cases, reduced formation. Interestingly, patterns alterations morphology differed between two transgenic models. Moreover, found accumulate intracellularly its content inversely correlated absolute relative mushroom spines. Collectively, our results suggest pathological mechanisms, namely an intracellular or extracellular plaques, may lead abnormalities adult respectively. These distinct features, represent very mechanisms synaptic failure AD, taken into consideration when translating from animal studies human disease.