Table 1.

Summary of studies investigating chronic voluntary physical activity in transgenic mouse models of Alzheimer's disease.

Model (Strain and Gender)	Physical Activity Type	Intensity (estimated) and Duration	Frequency	Major AD Outcomes	Reference
TgCRND8 Female	Wheel running	3.7–6.0 m/min 12 h/day	7 days/week 5 months From 1 to 6 months of age	↓ amyloid plaque ↑MWM	Adlard et al., 2005
APP23 Female	Wheel running	Multiple animals per cage w/single running wheel Distance run not reported	Beginning at 10 weeks of age Ending at 11 months of age	MWM (ns) Amyloid plaque (ns)	Wolf et al., 2006
APPsw Male or Female not specified	Wheel running	Multiple animals per cage w/single running wheel Distance run not reported	Beginning at 6 weeks of age Ending at 9 months of age	MWM (ns) RAWM (ns) Cortisol (ns) Cytokines (ns) Amyloid plaque (ns) Synaptophysin (ns)	Cracchiolo et al., 2007
Tg2576 Male or Female not specified	Wheel running	2.4 m/min 12 h/day	7 day/week 3 weeks Age ranged from 16 to 18 months at beginning of treatment	↓ soluble Aβ40 Aβ42 (ns) Aβ insoluble fraction (ns) ↓TNF-α and IL-1β	Nichol et al., 2008
Tg2576 Male and Female	Wheel running	12 h/day Distance run not reported	3 weeks in 16–18 month old mice	↑RAWM although performance similar to group with locked wheel	Nichol et al., 2007
Tg2576 Male or Female not specified	Wheel running	12 h/day Distance run not reported	7 days/week 3 weeks Age ranged from 15 to 19 months at beginning of treatment	Insoluble Aβ40 and Aβ42 (ns) ↑RAWM both reference and working memory	Parachikova et al., 2008
TgCRND8 Male	Wheel running Animals housed individually	2.0 m/min 12 h/day	7 days/week Treatment from 80 to 150 days of age (10 weeks)	NOR (ns) Barnes maze (ns) Spontaneous behavior (ns) Corticosterone (ns) Amyloid plaque (ns)	Richter et al., 2008
Tg2576 Male and Female	Wheel running	10.9 m/min 60 min/day	5 day/week 16 weeks From 5 to 9 months of age	↓amyloid plaque Soluble Aβ (ns) ↑NOR ↑hippocampal volume	Yuede et al., 2009
APP23 Female	Wheel Running	12 h/day	7 days/week 2 groups: Animals had access to running for 10 days one group was 6 months of age the other was 18 months of age	6 month group: No amyloid plaque present Adult hippocampal neurogenesis (ns) 18 month group: Amyloid plaque (ns) ↑ Adult hippocampal neurogenesis	Mirochnic et al., 2009
THY-Tau22 Male	Wheel Running	12 h/day Distance run not reported	7 days/week 9 months from 3 to 12 months of age	↑Y-Maze ↓pathological tau species Astrogliosis (ns) Inflammation (ns) Cholinergic neurons (ns) BDNF (ns)	Belarbi et al., 2011
3xTg-AD Male and Female	Wheel running	12 h/day Distance run not reported	7 days/week 2 groups: One month beginning at 3 months of age 6 months beginning at 1 month of age	1 month group: ↑MWM Corner test (ns) Open field (ns) Dark-light box test (ns) Boissier's 4 hole board test (ns) Soluble Aβ (ns) Amyloid plaque (ns) 6 month group: ↑MWM Corner test (ns) Open field (ns) Dark-light box test (ns) Boissier's 4 hole board test (ns) Soluble Aβ (ns) Amyloid plaque (ns) ↓oxidative stress	García-Mesa et al., 2011
3xTg-AD male	Wheel running	4.0 m/min 12 h/day	7 days/week 6 months from 6 to 12 months of age	↑MWM ↑sensorimotor function ↑dark-light box test ↑Boissier's hole board test ↓oxidative stress ↓amyloid plaque phosphorylated tau (ns)	García-Mesa et al., 2012
SAMP8 Female	Wheel running	0.55 m/min 12 h/day	7 days/week 8 weeks from 6 months of age to 8 months of age	↑growth factors in plasma and cortex Plasma triglycerides (ns)	Cosín-Tomás et al., 2014
3xTg-AD Male or Female Not specified	Wheel running	12 h/day distance not reported	7 days/week for 6 months from 1 to 7 months of age	↑Neuroprotective factors ↑synaptic proteins APP (ns) Tau (ns)	Revilla et al., 2014
3xTg-AD female	Wheel running	3.3 m/min 12 h/day	7 days/week 3 months from 12 to 15 months of age	↑MWM ↑locomotion ↑dark-light box test ↑Boissier's hole board test ↓oxidative stress ↓amyloid plaque ↓phosphorylated tau	García-Mesa et al., 2016
APPswe/PS1ΔE9 Male or Female not specified	Wheel Running	12 h/day Distance run not reported	7 days/week 10 weeks beginning at 5 months of age	↑MWM ↓Aβ oligomers ↓amyloid plaque ↓phosporylated tau ↓inflammation ↓neuronal cell loss ↑neurogenesis	Tapia-Rojas et al., 2016
TgCRND8 Male or Female not specified	Wheel Running	13.75 m/min 12 h/day	7 days/week Two groups: 1 month or running from 3 to 4 months of age 2 months of running from 3 to 5 months of age	1 month group: Open field (ns) ↑Y-Maze ↑ neurogenesis amyloid plaque area, size, and number (ns) 2 month group: ↑ Y-Maze ↓amyloid plaque area, size, and number ↑ neurogenesis	Maliszewska-Cyna et al., 2016

Abbreviations: MWM = Morris Water Maze, NOR = Novel Object Recognition, RAWM = Radial Arm Water Maze, BDNF = Brain Derived Neurotrophic Factor, APP = Amyloid Precursor Protein.

Clarifications:

1. In our experience mice exposed to running wheels 24 h per day, 7 days per week run in the wheel almost constantly during the 12 h dark cycle and almost not at all during the light cycle. Therefore, in this summary we report exercise duration as 12 h/day.

2. We estimated daily exercise intensity (speed) in studies that reported average distance run by dividing distance (meters) by 720 min (minutes in 12 h). This likely underestimates intensity slightly as the mice do not run constantly for the full 12 h dark cycle.

3. Several studies reported in this summary employed multiple groups as part of larger enrichment studies. For these studies, we only report findings comparing the group that only had access to a running wheel to the group receiving no enrichment.