Journal Article

DZNE-2023-01032

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Presymptomatic Reduction of Individuality in the AppNL-F Knockin Model of Alzheimer's Disease.

Ehret, F. (First author)DZNE* ; Pelz, M. S.DZNE* ; Senko, A. N.DZNE* ; Soto, K. E. G.DZNE* ; Liu, H.DZNE* ; Kempermann, G. (Last author)DZNE*

2023
Elsevier Science Amsterdam [u.a.]

This record in other databases:    

Please use a persistent id in citations: doi:10.1016/j.biopsych.2023.04.009

Abstract: One-third of the risk for Alzheimer's disease is explained by environment and lifestyle, but Alzheimer's disease pathology might also affect lifestyle and thereby impair the individual potential for health behavior and prevention.We examined in mice how the AppNL-F/NL-F (NL-F) knockin mutation affects the presymptomatic response to environmental enrichment (ENR) as an experimental paradigm addressing nongenetic factors. We assessed the emergence of interindividual phenotypic variation under the condition that both the genetic background and the shared environment were held constant, thereby isolating the contribution of individual behavior (nonshared environment).After 4 months of ENR, the mean and variability of plasma ApoE were increased in NL-F mice, suggesting a presymptomatic variation in pathogenic processes. Roaming entropy as a measure of behavioral activity was continuously assessed with radiofrequency identification (RFID) technology and revealed reduced habituation and variance in NL-F mice compared with control animals, which do not carry a Beyreuther/Iberian mutation. Intraindividual variation decreased, while behavioral stability was reduced in NL-F mice. Seven months after discontinuation of ENR, we found no difference in plaque size and number, but ENR increased variance in hippocampal plaque counts in NL-F mice. A reactive increase in adult hippocampal neurogenesis in NL-F mice, known from other models, was normalized by ENR.Our data suggest that while NL-F has early effects on individual behavioral patterns in response to ENR, there are lasting effects on cellular plasticity even after the discontinuation of ENR. Hence, early behavior matters for maintaining individual behavioral trajectories and brain plasticity even under maximally constrained conditions.

Keyword(s): Mice (MeSH) ; Animals (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Amyloid beta-Protein Precursor: genetics (MeSH) ; Amyloid beta-Peptides (MeSH) ; Individuality (MeSH) ; Mobile Applications (MeSH) ; Mice, Transgenic (MeSH) ; Disease Models, Animal (MeSH) ; Adult neurogenesis ; Dementia ; Hippocampus ; Learning ; Reserve ; Variability ; Amyloid beta-Protein Precursor ; Amyloid beta-Peptides

---

Contributing Institute(s):

1. Adult Neurogenesis (AG Kempermann)

Research Program(s):

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

Appears in the scientific report 2023

---

Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---