The effect of physical activity on cognition relative to APOE genotype (PAAD-2): study protocol for a phase II randomized control trial

Table 1 Biomarkers to be measured and potential mechanisms

Biomarker	Potential mechanism or proposed pathway
BDNF	Crucial role in plasticity of central and peripheral nervous systems [49]; Exercise responsive [50, 51]; Binds to tropomyosin-related kinase B (TrkB) receptor, ↑ glucose uptake, interacts with autonomic nervous system [42]
SAP	Biomarker of progression to AD [52, 53]
Albumin	Neuroprotective due in part to anti-oxidative properties [53, 54]
Glucose	Levels altered by exercise and related to irisin and/or BDNF; high levels have negative effect on neuroplasticity [55, 56]
IGF-I	Interacts with BDNF in response to exercise; neural plasticity [57,58,59]
APOE	Linked to Aβ clearance and lipid homeostasis [53, 60]
alpha-2 macroglobulin	Proteinase inhibitor associated with AD disease severity [53, 61]
Insulin	Altered by exercise and irisin; ↑ insulin sensitivity [62, 63]
Irisin	Exercise ↑ FNDC5/irisin release from muscle; ↑ BDNF transcription in hippocampus [42, 64, 65]
TNF-α	Pro-inflammatory [66, 67]; related to dementia [68, 69]

AD Alzheimer’s disease, APOE apolipoprotein epsilon 4 allele, BDNF Brain-derived neurotrophic factor, CRP C-reactive protein, FNDC5 fibronectin type III domain containing 5, IGF insulin-like growth factor, IL interleukin, SAP serum amyloid P, TNF Tumor necrosis factor

ISSN: 1471-2377