Complement 3 and factor H in human cerebrospinal fluid in Parkinson's disease, Alzheimer's disease, and multiple-system atrophy

Yu Wang; Aneeka M. Hancock; Joshua Bradner; Kathryn A. Chung; Joseph F. Quinn; Elaine R. Peskind; Douglas Galasko; Joseph Jankovic; Cyrus P. Zabetian; Hojoong M. Kim; James B. Leverenz; Thomas J. Montine; Carmen Ginghina; Karen L. Edwards; Katherine W. Snapinn; David S. Goldstein; Min Shi; Jing Zhang

doi:10.1016/j.ajpath.2011.01.006

Complement 3 and factor H in human cerebrospinal fluid in Parkinson's disease, Alzheimer's disease, and multiple-system atrophy

Yu Wang, Aneeka M. Hancock, Joshua Bradner, Kathryn A. Chung, Joseph F. Quinn, Elaine R. Peskind, Douglas Galasko, Joseph Jankovic, Cyrus P. Zabetian, Hojoong M. Kim, James B. Leverenz, Thomas J. Montine, Carmen Ginghina, Karen L. Edwards, Katherine W. Snapinn, David S. Goldstein, Min Shi, Jing Zhang

Neurology

Research output: Contribution to journal › Article › peer-review

91 Scopus citations

Abstract

Complement activation, a key component of neuroinflammation, has been reported in both Parkinson's disease (PD) and Alzheimer's disease (AD). However, it is unclear whether complement activation and neuroinflammation in general are distinctly different from each another in major neurodegenerative disorders. In the present study, cerebrospinal fluid complement 3 (C3) and factor H (FH) were measured and evaluated together with amyloid-β₄₂ (Aβ₄₂), which in recent investigations was decreased in patients with PD, in particular those with cognitive impairment. The study included 345 participants: 126 patients with PD at various stages with or without cognitive impairment, 50 with AD, and 32 with multiple-system atrophy, and 137 healthy control individuals. In addition to changes in Aβ₄₂ concentrations, there were clear differences in the patterns of complement profiles among neurodegenerative disorders. The C3/FH ratio demonstrated high sensitivity and specificity in differentiating patients with multiple-system atrophy from those with AD or PD and control individuals. In addition, the C3/Aβ₄₂ and FH/Aβ₄₂ ratios not only correlated with PD severity approximated using the Unified Parkinson's Disease Rating Scale but also with the presence of cognitive impairment or dementia in PD. Both C3 and FH correlated with the severity of impairment in AD as indicated using Mini-Mental State Examination scores.

Original language	English (US)
Pages (from-to)	1509-1516
Number of pages	8
Journal	American Journal of Pathology
Volume	178
Issue number	4
DOIs	https://doi.org/10.1016/j.ajpath.2011.01.006
State	Published - Apr 2011

ASJC Scopus subject areas

Pathology and Forensic Medicine

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10.1016/j.ajpath.2011.01.006

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Wang, Y., Hancock, A. M., Bradner, J., Chung, K. A., Quinn, J. F., Peskind, E. R., Galasko, D., Jankovic, J., Zabetian, C. P., Kim, H. M., Leverenz, J. B., Montine, T. J., Ginghina, C., Edwards, K. L., Snapinn, K. W., Goldstein, D. S., Shi, M., & Zhang, J. (2011). Complement 3 and factor H in human cerebrospinal fluid in Parkinson's disease, Alzheimer's disease, and multiple-system atrophy. American Journal of Pathology, 178(4), 1509-1516. https://doi.org/10.1016/j.ajpath.2011.01.006

Wang, Y, Hancock, AM, Bradner, J, Chung, KA , Quinn, JF, Peskind, ER, Galasko, D, Jankovic, J, Zabetian, CP, Kim, HM, Leverenz, JB, Montine, TJ, Ginghina, C, Edwards, KL, Snapinn, KW, Goldstein, DS, Shi, M & Zhang, J 2011, 'Complement 3 and factor H in human cerebrospinal fluid in Parkinson's disease, Alzheimer's disease, and multiple-system atrophy', American Journal of Pathology, vol. 178, no. 4, pp. 1509-1516. https://doi.org/10.1016/j.ajpath.2011.01.006

@article{e718cdb2f7d0494ca8197290d37ca06b,

title = "Complement 3 and factor H in human cerebrospinal fluid in Parkinson's disease, Alzheimer's disease, and multiple-system atrophy",

abstract = "Complement activation, a key component of neuroinflammation, has been reported in both Parkinson's disease (PD) and Alzheimer's disease (AD). However, it is unclear whether complement activation and neuroinflammation in general are distinctly different from each another in major neurodegenerative disorders. In the present study, cerebrospinal fluid complement 3 (C3) and factor H (FH) were measured and evaluated together with amyloid-β42 (Aβ42), which in recent investigations was decreased in patients with PD, in particular those with cognitive impairment. The study included 345 participants: 126 patients with PD at various stages with or without cognitive impairment, 50 with AD, and 32 with multiple-system atrophy, and 137 healthy control individuals. In addition to changes in Aβ42 concentrations, there were clear differences in the patterns of complement profiles among neurodegenerative disorders. The C3/FH ratio demonstrated high sensitivity and specificity in differentiating patients with multiple-system atrophy from those with AD or PD and control individuals. In addition, the C3/Aβ42 and FH/Aβ42 ratios not only correlated with PD severity approximated using the Unified Parkinson's Disease Rating Scale but also with the presence of cognitive impairment or dementia in PD. Both C3 and FH correlated with the severity of impairment in AD as indicated using Mini-Mental State Examination scores.",

author = "Yu Wang and Hancock, {Aneeka M.} and Joshua Bradner and Chung, {Kathryn A.} and Quinn, {Joseph F.} and Peskind, {Elaine R.} and Douglas Galasko and Joseph Jankovic and Zabetian, {Cyrus P.} and Kim, {Hojoong M.} and Leverenz, {James B.} and Montine, {Thomas J.} and Carmen Ginghina and Edwards, {Karen L.} and Snapinn, {Katherine W.} and Goldstein, {David S.} and Min Shi and Jing Zhang",

note = "Funding Information: Supported by grants ES004696 , NS057567 , AG025327 , AG033398 , and NS060252 (J.Z.), NS062684 (T.J.M., C.P.Z., J.B.L., and J.Z.), AG005136 (E.R.P. and T.J.M.), and AG008017 (K.A.C. and J.F.Q.) from the National Institutes of Health , and grants from the Michael J. Fox Foundation and the Cheng-Mei Shaw Endowment (J.Z.) and the Nancy and Buster Alvord Endowment (T.J.M.). ",

year = "2011",

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doi = "10.1016/j.ajpath.2011.01.006",

language = "English (US)",

volume = "178",

pages = "1509--1516",

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T1 - Complement 3 and factor H in human cerebrospinal fluid in Parkinson's disease, Alzheimer's disease, and multiple-system atrophy

AU - Wang, Yu

AU - Hancock, Aneeka M.

AU - Bradner, Joshua

AU - Chung, Kathryn A.

AU - Quinn, Joseph F.

AU - Peskind, Elaine R.

AU - Galasko, Douglas

AU - Jankovic, Joseph

AU - Zabetian, Cyrus P.

AU - Kim, Hojoong M.

AU - Leverenz, James B.

AU - Montine, Thomas J.

AU - Ginghina, Carmen

AU - Edwards, Karen L.

AU - Snapinn, Katherine W.

AU - Goldstein, David S.

AU - Shi, Min

AU - Zhang, Jing

N1 - Funding Information: Supported by grants ES004696 , NS057567 , AG025327 , AG033398 , and NS060252 (J.Z.), NS062684 (T.J.M., C.P.Z., J.B.L., and J.Z.), AG005136 (E.R.P. and T.J.M.), and AG008017 (K.A.C. and J.F.Q.) from the National Institutes of Health , and grants from the Michael J. Fox Foundation and the Cheng-Mei Shaw Endowment (J.Z.) and the Nancy and Buster Alvord Endowment (T.J.M.).

PY - 2011/4

Y1 - 2011/4

N2 - Complement activation, a key component of neuroinflammation, has been reported in both Parkinson's disease (PD) and Alzheimer's disease (AD). However, it is unclear whether complement activation and neuroinflammation in general are distinctly different from each another in major neurodegenerative disorders. In the present study, cerebrospinal fluid complement 3 (C3) and factor H (FH) were measured and evaluated together with amyloid-β42 (Aβ42), which in recent investigations was decreased in patients with PD, in particular those with cognitive impairment. The study included 345 participants: 126 patients with PD at various stages with or without cognitive impairment, 50 with AD, and 32 with multiple-system atrophy, and 137 healthy control individuals. In addition to changes in Aβ42 concentrations, there were clear differences in the patterns of complement profiles among neurodegenerative disorders. The C3/FH ratio demonstrated high sensitivity and specificity in differentiating patients with multiple-system atrophy from those with AD or PD and control individuals. In addition, the C3/Aβ42 and FH/Aβ42 ratios not only correlated with PD severity approximated using the Unified Parkinson's Disease Rating Scale but also with the presence of cognitive impairment or dementia in PD. Both C3 and FH correlated with the severity of impairment in AD as indicated using Mini-Mental State Examination scores.

AB - Complement activation, a key component of neuroinflammation, has been reported in both Parkinson's disease (PD) and Alzheimer's disease (AD). However, it is unclear whether complement activation and neuroinflammation in general are distinctly different from each another in major neurodegenerative disorders. In the present study, cerebrospinal fluid complement 3 (C3) and factor H (FH) were measured and evaluated together with amyloid-β42 (Aβ42), which in recent investigations was decreased in patients with PD, in particular those with cognitive impairment. The study included 345 participants: 126 patients with PD at various stages with or without cognitive impairment, 50 with AD, and 32 with multiple-system atrophy, and 137 healthy control individuals. In addition to changes in Aβ42 concentrations, there were clear differences in the patterns of complement profiles among neurodegenerative disorders. The C3/FH ratio demonstrated high sensitivity and specificity in differentiating patients with multiple-system atrophy from those with AD or PD and control individuals. In addition, the C3/Aβ42 and FH/Aβ42 ratios not only correlated with PD severity approximated using the Unified Parkinson's Disease Rating Scale but also with the presence of cognitive impairment or dementia in PD. Both C3 and FH correlated with the severity of impairment in AD as indicated using Mini-Mental State Examination scores.

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Complement 3 and factor H in human cerebrospinal fluid in Parkinson's disease, Alzheimer's disease, and multiple-system atrophy

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