. 2018 Feb 22;8:158–171. doi: 10.1016/j.ynstr.2018.02.004

Table 2.

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

Model (Strain and Gender)	Physical Activity Type	Intensity and Duration	Frequency	Major AD Outcomes	Reference
NSE/APPsw Male or Female not specified	Treadmill running	13.2 m/min, 0% grade 1 h/day	5 days/week 16 weeks Beginning at 13 months of age	↑MWM ↓ Aβ₄₂ deposition ↑BDNF and GLUT-1 ↑HSP70 ↑SOD and catalase ↓pro-apoptotic proteins	Um et al., 2008
NSE/APPsw Male or Female not specified	Treadmill running	13.2 m/min, 0% grade 1 h/day	5 days/week 16 weeks Beginning at 13 months of age	↑MWM ↓ Aβ₄₂ deposition ↑BDNF and GLUT-1 ↓pro-apoptotic proteins ↑HSP70 ↑SOD and catalase ↓Brain Total cholesterol, glucose, and insulin	Cho et al., 2010
NSE/hPS2m Male or Female not specified	Treadmill running	12 m/min, 0% grade 1 h/day 5 days/week	5 days/week 3 months Beginning at 24 months of age	↑MWM ↓ Aβ₄₂ deposition ↓tau phosporylation ↑BDNF, NGF, CREB ↑HSP70 ↑MAPK signaling ↓neuronal apoptosis	Um et al., 2011
NSE/hPS2m Male or Female not specified	Treadmill running	12 m/min, 0% grade 1 h/day	5 days/week 12 weeks Beginning at 24 months of age	↑MWM ↓Aβ₄₂ deposition ↓BACE-1 activity (β-secretase) ↓ER stress	Kang et al., 2013
3xTg-AD Male and Female	Treadmill running	4.2 m/min, 0% grade 30 min/day	5 days/week 5 weeks beginning at 6 months of age	Corner test (ns) Dark-Light box test (ns) MWM (ns) T-Maze (ns) ∼ Aβ₄₀; Aβ₄₂ (ns in females, improved ratio in males) Tau (ns)	Giménez-Llort et al., 2010
APP/PS1 Male or Female not specified	Treadmill running No electric shock motivation	5-11 m/min, 0% grade 30 min/day	5 days/week 5 months from 3 to 8 months of age	↑MWM ↑synaptic plasticity, LTP ↓BDNF mRNA	Liu et al., 2011
APP/PS1 Female	Treadmill running No electric shock motivation	5-11 m/min, 0% grade 30 min/day	5 days/week 5 months from 3 to 8 months of age	↓amyloid plaque ↓soluble Aβ₄₀ APP (ns) ↓sAPPβ, sAPPα (ns) ↓CTFα and CTFβ ↓hyperphosphorylated tau	Liu et al., 2013
APPswe/PS1dE9 Male	Treadmill running Gentle tail touching motivation no electric shock	Gradual distance increase 70–300 m/day with gradual speed increase from 5 to 8 to 10–15 m/min	6 days/week 5 months beginning at 4 months of age	↑MWM Amyloid plaque (ns) ↓microglial activation	Xiong et al., 2015
APP/PS1	Treadmill running No electric shock motivation	5-11 m/min, 0% grade 30 min/day	5 days/week 5 months 2 groups; one beginning at 3 months of age the other beginning at 12 months of age	Young group: ↑MWM ↓amyloid plaque ↓guanidine extracted soluble Aβ₄₀ and Aβ₄₂ ↑LTP Old group: ↑MWM Amyloid plaque in old mice (ns) ↓guanidine extracted soluble Aβ₄₀ and Aβ₄₂ ↑LTP	Zhao et al., 2015
APP/PS1 Male	Treadmill running Gentle tail touching motivation no electric shock	Week 1: 5 m/min, 0% grade 10 min/day Week 2: 10 m/min, 0% grade Time increased by 10 min each day Week 3–5: 10 m/min, 0% grade 60 min/day	5 days/week 5 weeks 2 groups; one beginning at 7 months of age the other at 24 months of age	Adult group: Passive avoidance (ns) ↓ anxiety MWM (ns) ↓guanidine extracted soluble Aβ₄₀ and Aβ₄₂ Few amyloid plaques detected in SED or EX BDNF (ns) Aged group: Passive avoidance (ns) Anxiety (ns) ↑MWM soluble Aβ₄₀ and Aβ₄₂ not assessed ↓ amyloid plaque	Ke et al., 2011
APP/PS1 Male	Treadmill running	11 m/min 30 min/day 0% grade	5 days/week 20 weeks; from 3 months of age to 8 months of age	↑ Y maze ↑ Passive Avoidance ↑ Mitochondrial function and antioxidant enzymes ↓ Mitochondrial ROS ↓ Aβ₄₂	Bo et al., 2014
APP/PS1 Male	Treadmill running	10 m/min 20 min/day 0% grade	5 days/week 4 months; from 6 months of age to 10 months of age	↑ MWM ↑ White matter capillary length and volume White matter capillary surface area (ns)	Zhang et al., 2017
3xTg-AD Male or Female not specified	Treadmill running Gentle tail touching motivation no electric shock	10 m/min 20 min/day 0% grade	5 days/week 12 weeks 2 groups; one beginning at 4 months of age the other beginning at 24 months of age	Young group: ↑MWM Aβ₄₀ and Aβ₄₂ (ns) Amyloid plaque (ns) APP (ns) Presenilin 1 (ns) CFTβ (ns) ADAM10&17 (ns) BACE1 (ns) IDE (ns) Neprilysin (ns) ↓phosporylated tau ↑PSD-95 and synaptophysin BDNF and NGF (ns) Old group: ↑MWM ↓ Aβ₄₀ and Aβ₄₂ ↓Amyloid plaque ↓APP ↓Presenilin 1 ↓BASE1 ↓ CFTβ ADAM10&17 (ns) BACE1 (ns) IDE (ns) Neprilysin (ns) ↓phosporylated tau ↑PSD-95 and synaptophysin ↑BDNF NGF (ns)	Cho et al., 2015
APPswe/PS1dE9 Male and Female	Treadmill running	Acclimation at 10 m/min 20–60 min/day first 4 weeks gradually increasing to 12 m/min 1hr/day 0% grade	5 days/week for 9 weeks beginning at 6 weeks of age	↑Conditioned fear memory ↑dendritic complexity ↑BDNF signaling pathways ↑LRP1 ↓Aβ₄₀ and Aβ₄₂	Lin et al., 2015
NSE/htau23 Male or Female not specified	Treadmill running	Acclimation at 9 m/min for 20 min/day Gradual increase from 12 m/min for 30 min/day to 14.4 m/min for 50 min/day 0% grade	5 days/week for 12 weeks	↑improved autophagy ↑GSK-3β ↓tau and phospho-tau ↑MWM	Kang and Cho, 2015
Tg-NSE/hPS2m Male or Female not specified	Treadmill running	12 m/min 1 h/day 0% grade	5 days/week for 3 months from 24 months of age	↑MWM ↑anti-apoptotic factors ↑insulin signaling pathways ↓COX-2 ↑BDNF ↑HSP70	Koo et al., 2013
3xTg-AD Male	Forced Wheel running	8 m/min 1 h/day 0% grade	2 groups: 1x/week or 3x/week for 12 weeks from 2.5 to 6 months of age	Improvement in blood and brain inflammatory chemokines in the 3x/week group, but not the 1x/week group	Haskins et al., 2016
Tg2576 Male and Female	Treadmill running	10.9 m/min, 0% grade 1 h/day	5 day/week 16 weeks From 5 to 9 months of age	↓amyloid plaque Soluble Aβ (ns) NOR (ns) ↑hippocampal volume	Yuede et al., 2009
Tg2576 Male	Treadmill running	Low Intensity group: 15 m/min 0% grade Hi Intensity group: 32 m/min 10% grade 1 h/day	5 days/week 3 months From 3 to 6 months of age	↓soluble Aβ₄₀ and Aβ₄₂ HI > LOW > SED ↑numerous Aβ clearance proteins HI > LOW > SED	Moore et al., 2016

Abbreviations: MWM = Morris Water Maze, APP = Amyloid Precursor Protein, BDNF = Brain Derived Neurotrophic Factor, HSP = Heat Shock Protein, CTF = C Terminal Fragment, SOD = Superoxide Dismutase, LTP = Long Term Potentiation, NGF = Nerve Growth Factor, ROS = reactive oxygen species.