Serum levels of inflammatory factors, such as C3, C4, C-reactive protein (CRP), immunoglobulin (Ig) G, IgA, and IgM, in patients with Alzheimer’s disease (AD) and their correlation with cognitive function remain unexplored.
Objective:
To investigate the expression of serum inflammatory factors in patients with AD and its correlation with cognitive function.
Methods:
Serum levels of C3, C4, CRP, IgG, IgA, and IgM in 200 patients with AD (mild, moderate, and severe) and those in 174 normal controls were assessed. Spearman’s rank correlation analysis was used to explore the relationships among biomarker levels, cognitive function, and activities of daily living (ADL).
Results:
Among these inflammatory factors, C3 and CRP levels were significantly lower, and IgG and IgA levels were significantly higher in the AD group than in the control group (p < 0.05). There were no significant differences in C4 and IgM levels between the two groups (p > 0.05). In all participants, CRP level was positively correlated with the Mini-Mental State Examination and Montreal Cognitive Assessment scores (p < 0.05). In the AD group, IgA level was negatively associated with ADL scores (p < 0.05). No significant correlation was detected between the other factors and different cognitive scores (p > 0.05).
Conclusion:
Inflammatory factors C3, CRP, IgG, and IgA have the potential to serve as biomarkers for AD. Furthermore, serum IgA was not only correlated with AD but also with ADL. These results support the hypothesis that inflammation is involved in the occurrence and development of AD.
JevticS, SengarAS, SalterMW, McLaurinJ (2017) The role of the immune system in Alzheimer disease: Etiology and treatment. Ageing Res Rev40, 84–94.
2.
SjobergAP, TrouwLA, BlomAM (2009) Complement activation and inhibition: A delicate balance. Trends Immunol30, 83–90.
3.
YasojimaK, SchwabC, McGeerEG, McGeerPL (1999) Up-regulated production and activation of the complement system in Alzheimer’s disease brain. Am J Pathol154, 927–936.
4.
StrohmeyerR, ShenY, RogersJ (2000) Detection of complement alternative pathway mRNA and proteins in the Alzheimer’s disease brain. Brain Res Mol Brain Res81, 7–18.
5.
RogersJ, CooperNR, WebsterS, SchultzJ, McGeerPL, StyrenSD, CivinWH, BrachovaL, BradtB, WardP, LieberburgI (1992) Complement activation by beta-amyloid in Alzheimer disease. Proc Natl Acad Sci U S A89, 10016–10020.
CrehanH, HardyJ, PocockJ (2012) Microglia, Alzheimer’s disease, and complement. Int J Alzheimers Dis2012, 983640.
8.
ZanjaniH, FinchCE, KemperC, AtkinsonJ, McKeelD, MorrisJC, PriceJL (2005) Complement activation in very early Alzheimer disease. Alzheimer Dis Assoc Disord19, 55–66.
9.
BiBT, LinHB, ChengYF, ZhouH, LinT, ZhangMZ, LiTJ, XuJP (2012) Promotion of beta-amyloid production by C-reactive protein and its implications in the early pathogenesis of Alzheimer’s disease. Neurochem Int60, 257–266.
SuC, ZhaoK, XiaH, XuY (2019) Peripheral inflammatory biomarkers in Alzheimer’s disease and mild cognitive impairment: A systematic review and meta-analysis. Psychogeriatrics19, 300–309.
12.
JackCR, AlbertMS, KnopmanDS, McKhannGM, SperlingRA, CarrilloMC, ThiesB, PhelpsCH (2011) Introduction to the recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement7, 257–262.
13.
SchmidtR, SchmidtH, CurbJD, MasakiK, WhiteLR, LaunerLJ (2002) Early inflammation and dementia: A 25-year follow-up of the Honolulu-Asia Aging Study. Ann Neurol52, 168–174.
14.
GabinJM, SaltvedtI, TambsK, HolmenJ (2018) The association of high sensitivity C-reactive protein and incident Alzheimer disease in patients 60 years and older: The HUNT study, Norway. Immun Ageing15, 4.
15.
O’BryantSE, JohnsonL, EdwardsM, SoaresH, DevousMD, RossS, RohlfingG, HallJ, Texas Alzheimer’s Research & Care Consortium (2013) The link between C-reactive protein and Alzheimer’s disease among Mexican Americans. J Alzheimers Dis34, 701–706.
ZaciragicA, LeparaO, ValjevacA, ArslanagicS, FajkicA, Hadzovic-DzuvoA, AvdagicN, AlajbegovicA, Mehmedika-SuljicE, CoricG (2007) Elevated serum C-reactive protein concentration in Bosnian patients with probable Alzheimer’s disease. J Alzheimers Dis12, 151–156.
18.
DemirciS, AynaliA, DemirciK, DemirciS, AridoganBC (2017) The serum levels of resistin and its relationship with other proinflammatory cytokines in patients with Alzheimer’s disease. Clin Psychopharmacol Neurosci15, 59–63.
19.
GongC, WeiD, WangY, MaJ, YuanC, ZhangW, YuG, ZhaoY (2016) A meta-analysis of C-reactive protein in patients with Alzheimer’s disease. Am J Alzheimers Dis Other Demen31, 194–200.
20.
NilssonK, GustafsonL, HultbergB (2011) C-reactive protein level is decreased in patients with Alzheimer’s disease and related to cognitive function and survival time. Clin Biochem44, 1205–1208.
21.
RobertsRO, GedaYE, KnopmanDS, BoeveBF, ChristiansonTJ, PankratzVS, KulloIJ, TangalosEG, IvnikRJ, PetersenRC (2009) Association of C-reactive protein with mild cognitive impairment. Alzheimers Dement5, 398–405.
22.
VintimillaR, HallJ, JohnsonL, O’BryantS (2019) The relationship of CRP and cognition in cognitively normal older Mexican Americans: A cross-sectional study of the HABLE cohort. Medicine (Baltimore)98, e15605.
23.
DikMG, JonkerC, HackCE, SmitJH, ComijsHC, EikelenboomP (2005) Serum inflammatory proteins and cognitive decline in older persons. Neurology64, 1371–1377.
24.
NorgaardI, NielsenSF, NordestgaardBG (2016) Complement C3 and high risk of venous thromboembolism: 80517 individuals from the Copenhagen General Population Study. Clin Chem62, 525–534.
25.
MaierM, PengY, JiangL, SeabrookTJ, CarrollMC, LemereCA (2008) Complement C3 deficiency leads to accelerated amyloid beta plaque deposition and neurodegeneration and modulation of the microglia/macrophage phenotype in amyloid precursor protein transgenic mice. J Neurosci28, 6333–6341.
26.
RasmussenKL, NordestgaardBG, Frikke-SchmidtR, NielsenSF (2018) An updated Alzheimer hypothesis: Complement C3 and risk of Alzheimer’s disease-A cohort study of 95,442 individuals. Alzheimers Dement14, 1589–1601.
WuW, YuE, RenA, ZhuL, ZhouJ (2010) Examinations of lymphocytes and inflammatory proteins in mild cognitive impairment. Shanghai Arch Psychiatry22, 147.
31.
XiaW, XuL, MiaoX (2020) Study of immunologic function in patients with Alzheimer’s Disease. Chinese J Health Lab Technol30, 77–79+82.
32.
Sparks SteinP, SteffenMJ, SmithC, JichaG, EbersoleJL, AbnerE, DawsonD, 3rd (2012) Serum antibodies to periodontal pathogens are a risk factor for Alzheimer’s disease. Alzheimers Dement8, 196–203.
33.
WilsonJS, MruthintiS, BuccafuscoJJ, SchadeRF, MitchellMB, HarrellDU, GulatiNK, MillerLS (2009) Anti-RAGE and A immunoglobulin levels are related to dementia level and cognitive performance. J Gerontol A Biol Sci Med Sci64, 262–271.
34.
SabharwalP, WisniewskiT (2014) Novel immunological approaches for the treatment of Alzheimer’s disease. Chinese J Contemp Neurol Neurosurg14, 139–151.
35.
DodelRC, DuY, DepboyluC, FrolichL, HaagA, HemmeterU, PaulsenS, TeipelSJ, BrettschneiderS, SpottkeA, NolkerC, MollerHJ, WeiX, FarlowM, SommerN, OertelW H (2004) Intravenous immunoglobulins containing antibodies against beta-amyloid for the treatment of Alzheimer’s disease. J Neurol Neurosurg Psychiatry75, 1472–1474.
