Neuronal localization of C1q in preclinical Alzheimer's disease

Maria I Fonseca,Claudia H Kawas,Juan C Troncoso,Andrea J Tenner

doi:10.1016/j.nbd.2003.09.004

Abstract

Complement has been postulated to contribute to inflammatory reactions associated with the neuropathology of Alzheimer's disease (AD). C1q, an initial component of the complement cascade, is associated with neuritic plaques and with neurons in the hippocampus of AD brain. Here, we report the presence of C1q in a cognitively intact subject, previously identified as preclinical AD. We compared in detail brain tissue of this preclinical case with a genetically related late-onset AD case. In the AD brain, C1q was typically associated with fibrillar Aβ plaques in frontal cortex and with plaques and neurons in the hippocampus. In the preclinical subject, C1q was abundantly present but it was cell-associated only, being primarily colocalized with neurons in both frontal cortex and hippocampus. However, no predominant cortical neuronal C1q localization was found in other preclinical cases or in Down's cases of different ages. Thus, it is possible that this neuronal-associated C1q reflects an early, but transient, response to injury that may modulate the progression of neurological dysfunction in AD.

Highlights

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with the loss of cognitive function and the presence of characteristic neuropathological changes that include synaptic and neuronal loss, neurofibrillary tangles, and extracellular senile plaques composed of h-amyloid (Ah) protein deposits
Immunohistochemical staining of frontal cortex from the preclinical case showed the presence of robust C1q immunostaining mainly associated with neurons (Figs. 1A and Postmortem interval for the mother/daughter subjects, and the controls for the same cause of death was about 36 h (Troncoso et al, 1998)
While neuronal-associated C1q is found in AD hippocampus (Afagh et al, 1996), little to no such neuronal C1q has been detected in frontal cortex in other brain areas in AD or other preclinical AD cases

Summary

Introduction

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with the loss of cognitive function and the presence of characteristic neuropathological changes that include synaptic and neuronal loss, neurofibrillary tangles, and extracellular senile plaques composed of h-amyloid (Ah) protein deposits. The association of complement proteins, as well as acute phase proteins and reactive glia, with senile plaques in AD brain, suggests that inflammatory processes may play a role in this disease (Akiyama et al, 2000; Rogers et al, 1996). In AD, C1q has been shown to be associated with fibrillar Ah plaques, and with tangles (PHF1 positive), but not with early tangles (AT-8 positive) (Afagh et al, 1996; Shen et al, 2001). It has been hypothesized that C1q, via activation of complement, can play a detrimental role in the development of AD pathology, promoting an inflammatory state via the recruitment of activated glial cells

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