Neural antigen–specific autoimmune disorders are immunotherapy responsive and affect all nervous system levels.^1-3 Subacute or insidious symptom onset raises suspicion for an infectious, degenerative, demyelinating, neoplastic or vascular disorder. Detection in serum or cerebrospinal fluid (CSF) of neuronal, glial, or skeletal muscle–specific IgG aids diagnosis and guides appropriate therapeutic options. Paraneoplastic cases reflect immune responses incited by onconeural antigens in an occult systemic cancer. Informative autoantibody profiles predict high cancer probability^4,5 and yield immunopathogenic insights. The Mayo Clinic Neuroimmunology Laboratory’s algorithm for neural-specific IgG detection incorporates a mouse tissue–based indirect immunofluorescence assay that, in 2% of evaluated cases, reveals clinically pertinent autoantibodies, some molecularly uncharacterized. We describe a novel autoantibody that yielded an astrocyte-restricted staining pattern.

In order to perform their normal physiological functions, it is important that cells maintain the intracellular pH within the physiological range. Intracellular enzyme activity, cytoskeleton component integration, and cellular growth and differentiation rates are all closely associated with the intracellular pH. It has been demonstrated that in nervous system diseases, such as ischemic stroke, traumatic brain injury, epilepsy, Parkinson's disease, and Alzheimer's disease (AD), the common characteristics are decreased pH or acidosis at both tissular and cellular levels. Particularly, some AD-associated enzymes will have altered activities under acidic conditions. We inferred that aging or ischemia may cause intracellular acidification. This acidification not only induces apoptosis but also substantially alters enzyme activities and promotes the development of AD or vascular dementia. The hypothesis of an intracellular pH role in sporadic AD or vascular dementia will be discussed in this paper. If confirmed, this hypothesis may lead to the formulation of new pathogenesis and new therapeutic approaches to AD or vascular dementia.