Is Alzheimer’s an Autoimmune Disease?
Previous studies have shown that ceramide levels are elevated in the brains of patients with Alzheimer’s disease—but now researchers believe higher levels of an antibody to this lipid may be a part of the disease model.
The new findings appear in the Journal of Alzheimer’s Disease.
“Ceramide and ceramide antibody can be detected in very early phases of plaque formation, long before cognitive deficits are visible in this Alzheimer’s mouse model,” says study author Erhard Bieberich, PhD, a professor in the Department of Neuroscience and Regenerative Medicine at the Medical College of Georgia at Georgia Regents University, in Augusta. “Therefore, we believe measuring levels of ceramide or ceramide antibodies can be used for early detection of Alzheimer’s disease.”
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While ceramide is synthesized in every cell in the human body, when it’s inside the brain, it appears to increase beta amyloid production and help the plaque kill brain cells in Alzheimer’s.
Because of that, researchers expected that creating antibodies against ceramide would impede plaque formation—and they were right. They published research showing that’s exactly what happened when they gave mice a drug that inhibited ceramide formation.
However, they were surprised to find that excessive ceramide had already gotten into the bloodstream and generated antibodies that actually supported disease progression, particularly in female mice.
Female Alzheimer’s mice treated with more ceramide experienced about a 33% increase in amyloid formation and their serum exosome levels increased 2.4 times.
“An increase of ceramide antibody in serum from the Alzheimer’s mouse model suggests that plaque formation and severity of the disease are correlated with this antibody,” Bieberich says. “Immunization with ceramide further increases antibody levels and plaque formation.”
Their evidence seems to add weight to the theory that Alzheimer’s is an autoimmune disease—which tend to be more common in women and is characterized by the immune system creating antibodies against the patient’s own tissue.
Based on their results, it’s unclear whether the anti-ceramide antibodies that may develop naturally during Alzheimer’s are a result of the disease or a cause of it.
“Since the ceramide antibody is likely to be caused by increased ceramide levels, reducing ceramide may prevent or reduce plaque formation,” Bieberich says. “Our next step is to test how reduction of ceramide affects Alzheimer’s disease using genetic and pharmacological methods.”
Building upon their first promising results published in the August 2014 issue of Neurobiology of Aging, Bieberich and his colleagues will expand the findings to include testing of cognitive improvements.
—Colleen Mullarkey
Reference
Dinkins MB, Dasgupta S, Wang G, Zhu G, He Q, Kong JN, Bieberich E. The 5XFAD mouse model of Alzheimer’s disease exhibits an age-dependent increase in anti-ceramide IgG and exogenous administration of ceramide further increases anti-ceramide titers and amyloid plaque burden. J Alzheimers Dis. 2015 Feb 26. [Epub ahead of print]