Journal Article

DZNE-2024-00045

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Localized APP expression results in progressive network dysfunction by disorganizing spike timing.

Viana-da-Silva, S. (First author)DZNE* ; Haberl, M.Extern* ; Gaur, K. ; Patel, R.Extern* ; Narayan, G. ; Ledakis, M. ; Fu, M. L. ; de Castro Vieira, M. ; Koo, E. H. ; Leutgeb, J. K. ; Leutgeb, S.

2024
Elsevier New York, NY

This record in other databases:    

Please use a persistent id in citations: doi:10.1016/j.neuron.2023.10.001

Abstract: Progressive cognitive decline in Alzheimer's disease could either be caused by a spreading molecular pathology or by an initially focal pathology that causes aberrant neuronal activity in a larger network. To distinguish between these possibilities, we generated a mouse model with expression of mutant human amyloid precursor protein (APP) in only hippocampal CA3 cells. We found that performance in a hippocampus-dependent memory task was impaired in young adult and aged mutant mice. In both age groups, we then recorded from the CA1 region, which receives inputs from APP-expressing CA3 cells. We observed that theta oscillation frequency in CA1 was reduced along with disrupted relative timing of principal cells. Highly localized pathology limited to the presynaptic CA3 cells is thus sufficient to cause aberrant firing patterns in postsynaptic neuronal networks, which indicates that disease progression is not only from spreading pathology but also mediated by progressively advancing physiological dysfunction.

Keyword(s): Mice (MeSH) ; Humans (MeSH) ; Animals (MeSH) ; Aged (MeSH) ; Amyloid beta-Protein Precursor: genetics (MeSH) ; Amyloid beta-Protein Precursor: metabolism (MeSH) ; Hippocampus: metabolism (MeSH) ; Neurons: physiology (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Synapses: physiology (MeSH) ; Mice, Transgenic (MeSH) ; Alzheimer’s disease ; Alzheimer’s disease ; Alzheimer’s disease ; Alzheimer’s disease ; Alzheimer’s disease ; Alzheimer’s disease ; amyloid precursor protein ; hippocampus ; phase precession ; spike timing ; theta oscillations ; Amyloid beta-Protein Precursor

---

Contributing Institute(s):

1. Cellular Circuits of Memory (AG Viana-da-Silva)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2024

---

Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---