Table 1 Effects of non-invasive therapy for Alzheimer’s disease
From: Therapeutic non-invasive brain treatments in Alzheimer’s disease: recent advances and challenges
Therapy | Effects of non-invasive therapy and underlying mechanisms |
|---|---|
PBM | • Improves spatial learning and memory [69, 70, 105] • Improves the auditory sentence comprehension [171] • Increases the ability of Aβ phagocytosis [69, 70] • Reduces the levels of Aβ1-40 and Aβ1-42 [69, 70] • Regulates microglia’s morphological transformation [70] • Upregulates VEGF levels to promote angiogenesis [69] • Alleviates the tau hyperphosphorylation [102] • Attenuates anxious-depressive-like behavior [92, 115,116,117] • Protects against neuronal damage, degeneration, and apoptosis [7] • Improves cerebral perfusion and resting-state functional connectivity [105] • Enhances mitochondrial cytochrome c oxidase (complex IV) activity [8, 22] • Preserves mitochondrial dynamic and inhibits mitochondrial fragmentation [102, 125, 126] • Recruits microglia around amyloid plaques and improves microglial phagocytosis [70] • Promotes the transformation of microglia from a neuroprotective to a neurotoxic phenotype and inhibits neuroinflammation [69, 102] • Inhibits oxidative stress and oxidative damage by activating NF-κB and PI3K/Akt pathway [125, 142,143,144,145] |
rTMS | • Improves learning and memory [171, 174, 176, 177] • Decreases Aβ accumulation and tauopathy [174, 175, 179] • Improved auditory sentence comprehension [175] • Regulates long-term potentiation/depression (LTP/LTD) by modulating the strength of Ca2+ internal flow and the intracellular Ca2+ level in the postsynaptic membrane [181] • Promotes neurogenesis and the differentiation of newborn cells into mature neurons [186] • Promotes the expressions of synaptic protein markers [178, 182] • Enhances brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B [178, 182] • Inhibits oxidative stress [223] • Regulates neurotransmitters and their receptors (e.g., 5-HT content, 5-HT receptors, dopamine, gamma-aminobutyric acid) [154, 199,200,201,202, 208] • Alleviates the impairment of synaptic plasticity [219] • Inhibits neuroinflammation through PI3K/Akt/NF-κB signaling pathway [219] • Exerts neurogenic and neuroprotective effects by improving the production of the brain-derived neurotrophic factors [177, 231] |
tDCS | • Improves cognitive function and reduces amyloid plaques [242, 251] • Improves cerebral blood flow [261] • Regulates synaptic plasticity by modulating membrane polarization, cortical excitability, and NMDA receptor [266] • Regulations on neurotransmitter systems [272,273,274] • Reduces the excessive activation of glial cells and inhibits neuroinflammation [251, 275] |
Exercise | • Alleviates learning and memory deficits and anxious-depressive-like behaviors [192, 286] • Increases cerebral blood flow [301, 302, 309] • Inhibits the release of inflammatory factors and gliosis [44, 286] • Promotes the transformation of astrocytes from neurotoxic A1 phenotype to neuroprotective A2 phenotype [311] • Promotes astrocytic brain-derived neurotrophic factor [313] • Promotes oxidative stress-related adaptations and alleviates oxidative damage [44, 286, 314] • Promotes Nrf2 DNA-binding activity [44] • Improves glymphatic clearance [319, 322, 325] • Enhances the activity of enzymes in ETC and the rates of mitochondrial respiration [328] • Induces mitochondrial adaptions to oxidative stress and improves the brain’s enzymatic antioxidant system [329] • Alleviates the damage of mtDNA [330] • Preserves mitochondrial dynamics and maintains mitochondrial homeostasis [331, 334] • Promotes the efficiency of mitochondrial quality control by improving the expressions of mitochondrial dynamics associated proteins [339] |