Table 1. Study on brain-derived neurotrophic factor and oxidative stress roles in Alzheimer’s disease by year order.
| Reference | Size (n) and Design | Diseases | Key findings |
|---|---|---|---|
| Yasutake et al. 125 | 60 AD, 60 VaD, 33 healthy elderly controls. Cross-sectional. | AD and VaD | Serum BDNF levels are significantly lower in AD groups than in VaD and controls group. BDNF plays pathological roles in AD, but further investigation is needed. |
| Laske et al. 126 | 15 early stages AD, 15 severe stages AD, 10 healthy elderly controls. Cross-sectional. | AD | Serum BDNF levels increased in the early stages of AD, reflecting the compensatory mechanism of early neurodegeneration, while in time, they will decrease, correlating with the severity of AD because of trophic support lacking and increasing Aβ plaque accumulation contributing to specific progressive degeneration in the affected brain region. BDNF in both groups is not detected in CSF because its level is below the detection limit. Further investigation is needed to define BDNF as an AD clinical diagnosis marker and for therapeutic monitoring. |
| Laske et al. 127 | 27 AD, 9 NPH, 29 healthy elderly controls. Cross-sectional. | AD and NPH | Significant decreases in BDNF serum levels in AD and NPH patients compared to healthy controls, reflecting a lack of trophic support and progressive neurodegeneration. BDNF serum levels did not correlate with MMSE, age, and CSF levels. No significant differences in BDNF levels in CSF in AD, NPH, and controls because of its low concentration. Further investigation is needed to explain the reasons for blood BDNF level reduction between AD and NPH patients. |
| Leyhe et al. 128 | 19 AD, 20 healthy elderly controls. Prospective cohort study. | AD | Serum BDNF levels were significantly decreased in the AD group before AChE-inhibitors treatment (10 mg Donepezil per day) and significantly increased after 15 months of treatment with no more significant difference from the control group. Down-regulation of BDNF begins with the first clinical symptoms and becomes persistent in the AD continuum, while up-regulation of BDNF happens along with the neuroprotective effect of AChE-inhibitor. |
| Angelucci et al. 115 | 86 AD, 54 aMCI and MCI-MD, 27 healthy elderly controls. Cross-sectional. | aMCI, MCI-MD, mild AD, and moderate-sever AD | BDNF has a potential role as a biomarker during the AD course, shown by an upregulation of BDNF serum levels that significantly increased in MCI and AD compared to healthy groups. However, the BDNF levels among aMCI, MCI-MD, mild AD, and moderate-severe AD are insignificantly different. Upregulation of BDNF is an early compensatory against neurodegeneration. |
| Forlenza et al. 116 | 30 AD, 71 MCI, 59 healthy elderly controls. Prospective cohort study. | AD and MCI | Decreased serum BDNF levels, along with a continuum of MCI to AD, indicate a reduced BDNF systemic availability that plays a role in the neurodegenerative process. The presence of the Met-BDNF allele and the APOE ε4 gene predict a worsened cognitive outcome in MCI patients. |
| O’Bryant et al. 129 | 198 AD, 291 controls. Prospective cohort study. | AD | Serum BDNF levels increased in the AD group associated with lower neuropsychological function on visual and verbal memory. Still, they had no significant difference in BDNF levels compared to the control group. |
| Sonali et al. 130 | 63 AD, 15 aMCI, 63 healthy elderly controls. Cross-sectional. | AD and aMCI | Serum BDNF levels were insignificantly higher in the AD group than in the aMCI group controls. BDNF was insignificantly different in genotype and allele distribution between the three groups and did not significantly affect MMSE score in AD and aMCI. Further investigation is needed to examine the potential of BDNF as an AD biomarker. |
| Ventriglia et al. 131 | 266 AD, 28 FTD, 40 LBD, 91 VaD, 30 PD, 169 healthy controls. Cohort retrospective and cross-sectional. | AD, FTD, LBD, VaD, and idiopathic PD. | BDNF levels decreased in several cognitive disorders as a non-specific marker for neurodegeneration. The use of psychotropic drugs during BDNF studies could create a confounding effect, therefore, needs to be controlled before BDNF analysis. BDNF can potentially be used as a new therapeutic target because it involves dementia and PD neuropathology. |
| Faria et al. 132 | 50 AD, 37 MC, 56 healthy elderly controls. Cross-sectional. | AD and MCI | AD patients showed a higher peripheral BDNF level reflecting a compensatory mechanism toward early neurodegeneration and related to immune cell activation (higher sTNFR1 and sICAM-1). Both peripheral BDNF and inflammatory markers are potentials to be an additional tool to differentiate cognitive impairment degrees. |
| Turana et al. 6 | 51 aMCI, 58 healthy elderly controls. Cross-sectional. | aMCI | Low plasma BDNF levels and the presence of the APOE ε4 gene improve the diagnostic value of aMCI diagnostic tool combination using pupillary response and olfactory test. |
| Liu et al. 133 | 110 AD, 120 healthy controls. Cross-sectional. | AD | Significantly lower serum BDNF levels in the AD group suggest an insufficient neurotrophic supply. BDNF levels were also significantly lower among all subjects in the AD group with APOE ε4 gene. BDNF possibly interacted with APOE ε4 and co-effects with MMSE scores. BDNF potential contributed to the molecular mechanism of the AD continuum. |
| Passaro et al. 134 | 44 late onset AD, 50 VaD, 23 CVD not dementia, 47 healthy controls. Cross-sectional. | AD, VaD, CVD not dementia | Plasma BDNF level in dementia (AD and VaD) groups affected by diabetes is the lowest among all subjects. BDNF levels affected by dementia synergically with diabetes status. |
| Ng et al. 135 | 2,067 AD and healthy control. Systematic review and meta-analysis. | AD | Serum BDNF levels were significantly lower in AD (excluding MCI) group than in controls with significant heterogenicity caused by age and MMSE scores as significant moderators during meta-regression analysis. Change in peripheral BDNF is only detected at the late stage of the AD continuum. Further investigation is needed, including molecular mechanisms, interventional trials, and BDNF potential use as an AD biomarker. |
| Mizoguchi et al. 136 | 256 elderlies with independent daily life without dementia. Cross-sectional observational study (2010 to 2016). | Memory impairment | Lower serum BDNF levels, older ages, lower physical activity, and hippocampal atrophy were associated with memory impairment independently. Impaired BDNF function (excluding proBDNF) combined with lower physical activity and hippocampal atrophy is associated with age-related memory impairment; therefore, BDNF is potentially used as a therapeutic target to prevent dementia. |
| Mori et al. 137 | 23 AD, 22 MCI, 21 healthy controls. Cross sectional. | AD and MCI | MCI group had significantly lower serum BDNF levels compared to the control group. AD group had a downward trend of serum BDNF levels than control group, but was not statistically significant. BDNF levels have a positive correlation with Aβ42 levels in CSF. The decreased serum BDNF levels could potentially be used as an AD early detection and progression biomarker. |
| Ng et al. 138 | 40 aMCI and non-aMCI, 56 healthy controls. Case-control. | aMCI, and non-aMCI | Plasma BDNF levels significantly increased in all MCI subjects with good discriminative accuracy as an early compensatory mechanism in preclinical dementia. BDNF is also correlated with neurotrophic and inflammation because it positively correlates with plasma high-sensitivity C-reactive protein. |
| Perkovic et al. 139 | 295 AD, 209 MCI. | AD and MCI | The increase in plasma BDNF levels in AD patients more significantly than in the MCI group might be due to counteracting mechanisms in the early-middle stage of neurodegeneration. |
Abbreviations: AChE, acetylcholinesterase; AD, Alzheimer’s disease; aMCI, amnestic mild cognitive impairment; BDNF, brain-derived neurotrophic factor; CSF, cerebrospinal fluid; CVD, cerebrovascular disease not dementia; FTD, frontotemporal dementia; LBD, Lewy body dementia; MCI, mild cognitive impairment; MCI-MD, multidomain mild cognitive impairment; MMSE, Mini-Mental State Examination; NPH, normal pressure hydrocephalus; PD, Parkinson’s disease; proBDNF, propeptide brain-derived neurotrophic factor; sICAM-1, Soluble intercellular adhesion molecule-1; sTNFR1, Soluble tumor necrosis factor receptor-1; VaD, vascular dementia.