This is pretty exciting. A discovery that points to why synapses disappear in Alzheimer's.
Destruction of synapses might be closer to the underlying disease process than simply amyloid accumulation.
Some with amyloid might somehow be protected against the C1q mediated loss of synapses.
Fortunately there are already antibodies against C1q and this is heading for the clinic.
Wonder whether a vaccine approach could be used for this.
http://huntingtonsdiseasenews.com/2016/ ... -diseases/
http://www.alzforum.org/news/research-n ... rs-disease
Might saving synapses preserve cognition in AD?
Re: Might saving synapses preserve cognition in AD?
J11, more research in the C1q world.
Slowpoke indeed! And then the cavalry has to show up to clean up the mess!
Since this pruning process starts before overt plaque deposition, it actually might be a good target for pharmaceuticals.
Also see http://www.ncbi.nlm.nih.gov/pubmed/27033548
http://scopeblog.stanford.edu/2016/08/2 ... -together/In another study, Barres and his associates found that a protein called C1q starts popping up on the surfaces of decrepit synapses as we age, rendering them increasingly vulnerable to getting chewed up by entirely different brain cells (called microglia) when the aging brain comes under inflammatory fire due to infection, head injury, a series of small strokes — or, tellingly, exposure to soluble A-beta clusters. The first brain regions showing dramatic increases in C1q are precisely those most vulnerable to neurodegenerative diseases like Alzheimer’s.
Barres’ newest study shows that different ApoE versions variously speed up or slow down the rate at which astrocytes thin the herd of unused synapses, with the “good” version (ApoE2) doing the best job of preventing C1q buildup and the “bad” version (ApoE4) doing the worst. The study suggests that speeding up astrocytes is a good thing, as APoE2, a whiz at clearing slacker synapses and preventing C1q accumulation, is correlated with a lower Alzheimer’s risk, while slowpoke ApoE4, which leaves a host of C1q-prone synapses in its wake, leads to a higher Alzheimer’s risk.
Slowpoke indeed! And then the cavalry has to show up to clean up the mess!
Since this pruning process starts before overt plaque deposition, it actually might be a good target for pharmaceuticals.
Also see http://www.ncbi.nlm.nih.gov/pubmed/27033548
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Re: Might saving synapses preserve cognition in AD?
Perhaps this C1q pruning is a factor in the brain changes seen even before birth and through early adulthood in APOE4's:
http://www.alzforum.org/news/research-n ... begin-womb
http://www.wsj.com/articles/alzheimers- ... 1468440000
http://www.alzforum.org/news/research-n ... begin-womb
http://www.wsj.com/articles/alzheimers- ... 1468440000
Re: Might saving synapses preserve cognition in AD?
Really interesting...
From the pubmed article discussing the study led by Beth Stevens:
From the pubmed article discussing the study led by Beth Stevens:
Which makes me wonder also if some of the success seen in the recent trials of Biogen's Aducanumab (discussed in a couple of earlier threads) has to do with the drug's apparent ability to target toxic soluble oligomers as well an insoluble fibrils (& leaving the protective monomers alone). Just thinking a reduction in soluble AB oligomers would mean that the presence of C1q would be less damaging...?C1q is necessary for the toxic effects of soluble β-amyloid (Aβ) oligomers on synapses and hippocampal long-term potentiation.
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Re: Might saving synapses preserve cognition in AD?
Here's a great layperson's overview of Beth Steven's research:
http://www.sciencemag.org/news/2016/08/ ... s-synapses
http://www.sciencemag.org/news/2016/08/ ... s-synapses
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Re: Might saving synapses preserve cognition in AD?
ArticWolf,
Thank you for posting the layperson's overview of Beth Steven's research. It is a big help for us non-scientific folk to understand the idea.
It certainly is interesting.
Starfish
Thank you for posting the layperson's overview of Beth Steven's research. It is a big help for us non-scientific folk to understand the idea.
It certainly is interesting.
Starfish
Re: Might saving synapses preserve cognition in AD?
Wolfie, thx for the sciencemag link re: Beth Steven's research. I did a search and didn't see this one. The chronology of how the story of C1q developed is just fascinating.