Patients with Alzheimer disease have elevated intrathecal synthesis of antibodies against tau protein and heavy neurofilament.

The role of humoral immunity related to neuron- and disease-specific cytoskeletal proteins patients with Alzheimer disease (AD) is unknown. We measured antibodies against tau protein, light and heavy (NFH) neurofilaments using ELISA in 80 paired serum and cerebrospinal fluid (CSF) samples from patients with AD, with other dementias (OD), with neuro-inflammatory diseases (IC) and 25 controls (NC). We estimated intrathecal synthesis according to the formula (CSF/serum anti-neurocytoskeletal IgG)/(CSF/serum total IgG). AD patients had significantly higher intrathecal anti-tau and anti-NFH antibodies than the other groups. These innovative findings may hint at specific alterations in humoral anti-neurocytoskeletal immunity and selectivity in AD, which could have diagnostic and immunotherapeutic implications.