Cascade Biotechnology INC | Complement Therapeutics; novel approach to CNS/PNS disease management using the innate complement system.

Cognitive Disorders: Alzheimer's Disease

The complement system facilitates the immune response to destroy and remove pathogens. In aging and potentially Alzheimer’s disease, complement influences beta-amyloid, tau and APOe4 interactions.
Complement protein C3 plays a major role in complement activation and control of immune responses.
The complement cascade, of which C3 is a common central component, is part of the innate immune system and mediates the phagocytic removal of pathogens and cellular debris, as well as cell membrane lysis. (Fujita, 2002, Stevens et al., 2007; Schafer et al., 2012).
In postnatal brain, C3 and complement protein C1q localize to synapses and facilitate glial mediated elimination of immature synapses.
This occurs during developmental refinement of the visual system (Stevens et al., 2007; Schafer et al., 2012).
Complement proteins also play a role in the adult and aging brain. C1q protein increases significantly in both aging and human and mouse brains (Stephan et al., 2013) and colocalizes with synapses in brain areas vulnerable to degeneration.
Adult C1q knock-out (KO) mice show enhanced activity-dependent synaptic potentiation (Stephan et al., 2013).
Also in aging human C3 gene expression is upregulated. (Cribbs et al., 2012).
Synaptic degeneration in aging often precedes neurodegenerative disease and neuron loss (Morrison and Baxter, 2012).
C1q is upregulated with aging, even though it may not mediate synapse elimination (Stephan et al., 2013).
C3 may however be an initiating factor of the alternative complement pathway, and promote synapse loss during aging.
Current research indicates C3, C1q and possibly other complement proteins are involved with Alzheimer’s disease potentially influencing beta-amyloid, tau and APOe4.
Thus C3 appears to be involved with mediating synaptic function and aging brain plasticity.
Synapse loss in Alzheimer's disease (AD) correlates with cognitive decline.
Involvement of microglia and complement in AD has been attributed to neuroinflammation, prominent late in disease.
This makes C3 and C1q potentially important targets within the complement system.

Hong et al., (2016). Complement and Microglia Mediate Early Synapse Loss in Alzheimer Mouse. Science May 6; 352(6286): 712–716.

Shi et al. (2015). Complement C3-Deficient Mice Fail to Display Age-Related Hippocampal Decline. The Journal of Neuroscience 35(38):13029 –13042.

Brucato F.H, Benjamin D.E. (2020). Synaptic Pruning in Alzheimer's Disease:Role of the Complement System. Global Journal of Medical Research F:Diseases Volume 20 Issue 6 Version1.0. ISSN: 2249-4618 & Print ISSN:0975-5888.

Alzheimer's disease

Cascade Biotechnology INC | Complement Therapeutics; novel approach to CNS/PNS disease management using the innate complement system.

Cognitive Disorders: Alzheimer's Disease

The complement system facilitates the immune response to destroy and remove pathogens. In aging and potentially Alzheimer’s disease, complement influences beta-amyloid, tau and APOe4 interactions.

Complement protein C3 plays a major role in complement activation and control of immune responses.

The complement cascade, of which C3 is a common central component, is part of the innate immune system and mediates the phagocytic removal of pathogens and cellular debris, as well as cell membrane lysis. (Fujita, 2002, Stevens et al., 2007; Schafer et al., 2012).

In postnatal brain, C3 and complement protein C1q localize to synapses and facilitate glial mediated elimination of immature synapses.

This occurs during developmental refinement of the visual system (Stevens et al., 2007; Schafer et al., 2012).

Complement proteins also play a role in the adult and aging brain. C1q protein increases significantly in both aging and human and mouse brains (Stephan et al., 2013) and colocalizes with synapses in brain areas vulnerable to degeneration.

Adult C1q knock-out (KO) mice show enhanced activity-dependent synaptic potentiation (Stephan et al., 2013).

Also in aging human C3 gene expression is upregulated. (Cribbs et al., 2012).

Synaptic degeneration in aging often precedes neurodegenerative disease and neuron loss (Morrison and Baxter, 2012).

C1q is upregulated with aging, even though it may not mediate synapse elimination (Stephan et al., 2013).

C3 may however be an initiating factor of the alternative complement pathway, and promote synapse loss during aging.

Current research indicates C3, C1q and possibly other complement proteins are involved with Alzheimer’s disease potentially influencing beta-amyloid, tau and APOe4.

Thus C3 appears to be involved with mediating synaptic function and aging brain plasticity.

Synapse loss in Alzheimer's disease (AD) correlates with cognitive decline.

Involvement of microglia and complement in AD has been attributed to neuroinflammation, prominent late in disease.

This makes C3 and C1q potentially important targets within the complement system.

See also:

Hong et al., (2016). Complement and Microglia Mediate Early Synapse Loss in Alzheimer Mouse. Science May 6; 352(6286): 712–716.

Shi et al. (2015). Complement C3-Deficient Mice Fail to Display Age-Related Hippocampal Decline. The Journal of Neuroscience 35(38):13029 –13042.

Brucato F.H, Benjamin D.E. (2020). Synaptic Pruning in Alzheimer's Disease:Role of the Complement System. Global Journal of Medical Research F:Diseases Volume 20 Issue 6 Version1.0. ISSN: 2249-4618 & Print ISSN:0975-5888.