Dataset

DZNE-2026-00278

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset: Over-expression of human mutated APP transgene in the mouse brain induces differential gene expression profiles depending on the age of exposure

Xie, K.DZNE* ; Ryan, D. ; Bonn, S. ; Ehninger, D.DZNE*

2026
Gene Expression Omnibus

Abstract: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder causing about two third of all dementia cases in the elderly. Although AD pathological features have been intensively examined in numerous scientific studies employing invertebrate and vertebrate model organisms, the exact underlying mechanisms remain poorly understood. Extracellular accumulation of amyloid beta (Aβ) peptides represents a pathological hallmark of AD and it has been considered as the initiation point of AD by the popular amyloid hypothesis. In the current study, we aim to address whether expression of a mutated APP transgene (APPSweInd) would provoke differential neurological outcomes depending on the age of exposure in mice. Towards this end, we employed a tetracycline-based inducible genetic system to target APPSweInd transgene expression to defined age intervals initiated at adulthood, i.e., between 6-18 months (= mid-aged group) and 12-24 months (= aged group). Surprisingly, over-expression of mutant APP reduced the transcriptional levels of genes embedded in the cholinergic network exclusively in the aged mouse brain, while gene expression profiles related to inflammatory activation and exacerbated gliosis were shared between age groups. Hence, our data support the notion that AD pathology may rely on a disruption of the cholinergic system that is triggered through an altered response of the aged brain towards toxic Aβ aggregates.

---

Contributing Institute(s):

1. Translational Biogerontology (AG Ehninger)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

---

---

Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Journal Article Xie, K. (First author)DZNE* ; Ryan, D.DZNE* ; Schröder, S.DZNE* ; Freund, L.DZNE* ; Bonn, S. ; Zhou, Y. ; Ehninger, D. (Last author)DZNE*
Selective vulnerability of the aging cholinergic system to amyloid pathology revealed by induced APP overexpression.
Journal of neuroinflammation 23(1), 39 (2026) [10.1186/s12974-025-03682-2]2026   Files  Fulltext by Pubmed Central BibTeX | EndNote: XML, Text | RIS

---