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The mediating role of inflammation in the relationship between α‐synuclein and cognitive functioning
Author(s) -
Dabiri Sanaz,
Ruiz Mara Ramirez,
Obisesan Thomas O.,
Ntekim Oyonumo,
Mwendwa Denée T.,
Ngwa Julius S.,
Campbell Alfonso L.
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.052597
Subject(s) - cognitive decline , mediation , inflammation , medicine , cerebrospinal fluid , cognition , neuroimaging , psychology , disease , effects of sleep deprivation on cognitive performance , oncology , endocrinology , dementia , neuroscience , political science , law
Background Accumulating evidence suggests that α‐synuclein is associated with poor cognitive functioning and plays a role in the pathophysiology of AD. High accumulation of α‐synuclein eventually leads to neuronal death and the initiation of inflammatory cascades. Prior research suggests inflammation plays a role in the development and acceleration of cognitive decline. Moreover, recent studies suggest VEGF may be involved in the development of AD. Therefore, this study examined whether α‐synuclein in cerebrospinal fluid (CSF) was associated with cognitive functioning among older adults. We also determined whether this relationship was influenced by elevated levels of pro‐inflammatory cytokines TNFα, IL‐6, soluble IL‐6 receptor along with VEGF. Method Using a cross‐sectional Alzheimer’s Disease Neuroimaging Initiative (ADNI; n= 148) sample, we examined the relationship between CSF measured α ‐ synuclein and participants' performance on MMSE and ADAS‐Cog 13 at baseline. Mediation analyses while adjusting for age, education, APOEe4, and GDS scores were utilized. Result Participants in the current sample were largely males (58.3%), Caucasian (95.5%), average education of 15.5 (SD = 2.97) years and average age 74.4 (SD = 7.51). We observed that higher accumulation of α ‐ synuclein was associated with lower performance on the MMSE (β =‐.41, SE=1.54, p <.001). This relationship was also mediated by VEGF (β =.27, SE=2.15, p =.025) and IL‐6r (β =.22, SE=1.66, p <.026). In addition, α ‐ synuclein was associated with poorer performance on the ADAS‐Cog 13 (β =0.34, p =.005) and mediated by VEGF (β =‐.19, SE=4.13, p =.025) after adjusting for age, education, APOEe4, and depressive symptoms. Conclusion Our findings suggest that α‐synuclein can be used as an additional biomarker for poor cognitive functioning. VEGF and IL‐6 soluble receptors were significant mediators in the relationship between α‐synuclein and cognitive functioning. However, this study observed that pro‐inflammatory cytokines TNFα and IL‐6 did not mediate this relationship. If confirmed in prospective analyses, these findings can further inform the pathologic cascade and early diagnosis of AD.