Detection of circulating antibodies against tau protein in its unphosphorylated and in its neurofibrillary tangles-related phosphorylated state in Alzheimer's disease and healthy subjects.

While the presence of naturally occurring antibodies (Abs) against amyloid-beta in AD patients and healthy subjects have been repeatedly reported, no data on the presence of naturally occurring Abs against tau protein, in its unphosphorylated as well as its pathologically phosphorylated state, has been reported so far. We describe here the detection of circulating Abs against unphosphorylated and pathologically phosphorylated tau protein in sera of 17 aged subjects: nine Alzheimer's disease (AD) patients and eight healthy individuals. An ongoing autoimmune process may take place, as is suggested by the presence of both IgM class anti-tau Abs, as well as IgG. A preliminary evidence for higher anti-phosphorylated-tau Abs of IgM class in AD patients relative to controls is indicated, but demands further confirmation in a larger sample. Detection of naturally occurring anti-tau antibodies may point to the possibility that some autoimmune process may take place against the tau neuronal protein, including its pathologically phosphorylated state which compose the neurofibrillary tangles. Whether these Abs are neuroprotective or neurotoxic - is unknown, as it is with anti-amyloid-beta Abs.