Presymptomatic Reduction of Individuality in the AppNL-F Knockin Model of Alzheimer's Disease

Research output: Contribution to journalResearch articleContributedpeer-review



Background: 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. Methods: 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). Results: 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. Conclusions: 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.


Original languageEnglish
Pages (from-to)721-731
Number of pages11
JournalBiological psychiatry
Issue number9
Publication statusPublished - 1 Nov 2023

External IDs

PubMed 37076091
ORCID /0000-0002-5304-4061/work/150328880
ORCID /0000-0003-4820-0979/work/150330820


Research priority areas of TU Dresden

Sustainable Development Goals

ASJC Scopus subject areas


  • Adult neurogenesis, Dementia, Hippocampus, Learning, Reserve, Variability, Alzheimer Disease/genetics, Mice, Transgenic, Animals, Amyloid beta-Protein Precursor/genetics, Amyloid beta-Peptides, Individuality, Mice, Disease Models, Animal

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