Late running is not too late against Alzheimer's pathology.
In the last decade a vast number of animal studies have produced overwhelming evidence that exercise not only compensates for memory loss by increasing brain plasticity and cognitive reserve but also directly counteracts Alzheimer-like pathology when provided before disease onset or in early disease stages. But so far, there is little knowledge about therapeutic effects of training when started in advanced disease stages. In the present study we show that following seven months of sedentary life style five months of wheel running, started four months after disease onset was still able to mitigate at least some aspects of the full-blown Alzheimer's pathology in TgCRND8 mice. Late running had mild but significant effects on structural plasticity by increasing the dendritic complexity. It further reduced beta-amyloid (Aβ) plaque burden and enhanced Aβ clearance across the blood-brain barrier, along with attenuating microgliosis, inflammation, oxidative stress, and autophagy deficits, resulting in better memory performance and less agitation. However, unlike early exercise, late running did not affect abnormal amyloid precursor protein metabolism, tau pathology, or angiogenesis. These results allow concluding that it is never too late to counteract Alzheimer's disease with physical training but the earlier the intervention starts, the more pronounced is the therapeutic potential.
Institute of Neuropathology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Arne
A
Herring
Institute of Neuropathology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Yvonne
Y
Münster
Institute of Neuropathology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Judith
J
Metzdorf
Institute of Neuropathology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Bastien
B
Bolczek
Institute of Neuropathology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Sarah
S
Krüssel
Institute of Neuropathology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
David
D
Krieter
Institute of Neuropathology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Ilkay
I
Yavuz
Institute of Neuropathology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Fro
F
Karim
Institute of Neuropathology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Constanze
C
Roggendorf
Institute of Neuropathology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Anthony
A
Stang
Department of Neurology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Yachao
Y
Wang
Department of Neurology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Dirk M
DM
Hermann
Institute of Neuropathology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany.
Sarah
S
Teuber-Hanselmann
Institute of Neuropathology, University of Duisburg-Essen, Hufelandstr. 55, 45122 Essen, Germany. Electronic address: kathy.keyvani@uk-essen.de.
Kathy
K
Keyvani
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D058225:Plaque, Amyloid / Q000378:metabolism; D012420:Running; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins
Alzheimer's disease; Aβ metabolism; Inflammation & autophagy; Late physical activity; Neuroplasticity