Tracking early signs of Alzheimer's pathology in a mouse model
Behavioral interventions may alter trajectory

Date:
May 31, 2023
Source:
Elsevier
Summary:
About two-thirds of the risk for Alzheimer's disease (AD) is
thought to arise from genetic influences, but about a third
could be influenced by environment and lifestyle, opening the
door for behavioral interventions that could delay or prevent
pathophysiological changes that occur with AD. Now a new study in a
mouse model of AD examines the effects of environmental enrichment
on AD symptom progression and pathology.


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FULL STORY ========================================================================== About two-thirds of the risk for Alzheimer's disease (AD) is thought to
arise from genetic influences, but about a third could be influenced by environment and lifestyle, opening the door for behavioral interventions
that could delay or prevent pathophysiological changes that occur with
AD. Now a new study in a mouse model of AD examines the effects of environmental enrichment on AD symptom progression and pathology. The
study appears in Biological Psychiatry, published by Elsevier.

Gerd Kempermann, PhD, from the German Center for Neurodegenerative
Diseases in Dresden, Germany, and senior author of the study, emphasized
the importance of studying the early stages of disease, when interventions might be most effective.

Dr. Kempermann commented, "AD does not start when the symptoms become
obvious.

There is a decades-long silent period, during which the pathology
progresses undetected. Clinicians and researchers have become increasingly interested in what happens during this phase." To study this early
pathology, Dr. Kempermann and colleagues used a mouse model of AD that replicates this silent period. The model contains several mutations
associated with human AD in the gene encoding amyloid precursor protein
(App).

These AppNL-F mice develop toxic amyloid-beta plaques by age 6 months
and cognitive impairment by 18 months.

Dr. Kempermann said, "However, we discovered that there are already subtle
but important behavioral changes long before the first plaques appear,
and the cognitive deficits become detectable." The mice were housed
in an enriched environment, which consisted of 60 interconnected cages,
from age 6 weeks to 23 weeks and were then moved to standard cages after
4 months. Living in the enriched environment improved several measures
of metabolism, which are known risk factors for AD.

Dr. Kempermann explained, "The [AD model] mice in our study showed
a reduction in individual behaviors. They became more similar and
more rigid. As this individualization is to a large degree driven by
individual behavior and depends on brain plasticity, we can conclude
that the affected mice had behavioral deficits very early in the
course of the disease. They did not respond normally to the offerings
of their environment. This finding is important, because it will help
us to understand how we can best tailor preventive measures during
the pre-clinical phase. It also underscores that prevention has to
start early." The researchers also examined markers of neurogenesis in
the mice.

Paradoxically, the AppNL-F mice had higher rates of neurogenesis than
control mice, which is interpreted as a failing attempt at compensation
and as paradoxically counterproductive. This overshooting compensation
was normalized by exposure to enrichment.

John Krystal, MD, Editor of Biological Psychiatry, said of the work,
"This novel study suggests that environmental enrichment may reduce
the early accumulation of amyloid plaques in a mouse model of AD. This
insight may suggest a strategy for delaying the development of symptoms associated with this disorder."
* RELATED_TOPICS
o Health_&_Medicine
# Alzheimer's_Research # Healthy_Aging #
Parkinson's_Research # Chronic_Illness
o Mind_&_Brain
# Alzheimer's # Dementia # Behavior # Huntington's_Disease
* RELATED_TERMS
o Alzheimer's_disease o Mouse o Personalized_medicine o
Delayed_puberty o Dementia_with_Lewy_bodies o Animal_cognition
o Homosexuality o House_mouse

========================================================================== Story Source: Materials provided by Elsevier. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Fanny Ehret, Meike S. Pelz, Anna N. Senko, Karla E.G. Soto,
Hang Liu,
Gerd Kempermann. Pre-symptomatic reduction of individuality in
the App NL-F knock-in model of Alzheimer's disease. Biological
Psychiatry, 2023; DOI: 10.1016/j.biopsych.2023.04.009 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/05/230531150058.htm

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