Tottori J. Clin. Res. 9(1), XX-XX, 2017

Reduced CD59 expression is associated with high membrane attack complex(MAC) levels in neurons of Alzheimer’s disease
Yuki Shimoda1), Yoshihiro Konishi1), Lucia I. Sue2), Thomas G. Beach2), Yong Shen3)
1) Department of Clinical Research, NHO Tottori Medical Center
2) Brain and Body Donation Program and Department of Neuropathology,
Banner Sun Health Research Institute3) Center for Advanced Therapeutic Strategies for Brain Disorders, Roskamp Institute*Correspondence: ykonishi@tottori-iryo.hosp.go.jp
Abstract
Complement proteins, including C1q, factor B, and the membrane attack complex (MAC), have beenreported to be activated and play important roles in Alzheimer’s disease (AD) brain. However, it remains
controversial whether the expression of CD59, which regulates the terminal complement pathway and thus
prevents the formation of lytic MAC, is upregulated or deficient in the AD brain. In this study, we used double
immunofluorescence labeling to demonstrate that neurons in AD brains lacked CD59, whereas CD59 waspresent almost all neurons in the low pathology control (LPC) brains. In the high pathology control (HPC)
brains, 20 ‒ 45% of neurons were positive for CD59. We also observed that many neurons in the AD brains
were positive for MAC, whereas almost all neurons in the LPC brains lacked MAC. In the HPC brains, 10% orfewer neurons were positive for MAC. These results indicate that labeling of MAC in neurons is associatedwith deficient CD59 expression in neurons in AD brains. Moreover, the changes in CD59 (55 ‒ 80% reduction)and MAC (10% or fewer positive) in neurons observed in HPC individuals, who are an intermediate subset
between the AD and LPC stages, indicate that changes in CD59 start to occur in the early stage of AD. Thesechanges likely precede the completion of terminal complement activation in the brain, although it is uncertain
whether reduced expression of CD59 or production of MAC occurs earlier. Tottori J. Clin. Res. 9(1), XX-XX,
2017
Keywords: neuroinflammation, complement proteins, membrane attack complex (MAC), CD59, Alzheimer’s
disease (AD)Introduction
Numerous inflammatory mediators havebeen identified in AD brains but not detected inelderly individuals without dementia [1].
Mountingevidencesuggests
thatneuroinflammation
isinvolvedin
thepathogenesis of AD [2,3]. In particular, thecomplement system has been shown to play
important roles. While both the classical andalternative complement pathways contribute to
the pathogenesis of AD [4], evidence is lacking
for a direct involvement of the lectin pathway [5].
Complement proteins such as C1q, factor B, andtheMAC(C5b‒9)have
been
immunohistochemically identified in β-amyloid(Aβ)-positive plaques and in phosphorylated tau(p-tau)-positive tangles in the AD brain [6‒9]. In
addition, Aβ and p-tau have been reported toactivate the complement system in AD [10‒12] ina unique manner that is Aβ- and p-tau-mediatedand antibody-independent, the effect of whichlead to neurodegeneration in AD [10,13].
Several defense or regulatory proteins
control complement activation [13,14], and thesefall into two distinct groups. The first group
comprises inhibitors of the complement pathways