Cerebrospinal fluid microglial antibodies: potential diagnostic markers for immune mechanisms in Alzheimer's disease.

Hallmark lesions of Alzheimer's disease (AD) are filled with reactive immunocompetent microglia, suggesting that immunological aberrations may participate in the pathophysiology of this disorder. Microglia may participate in the initial stages of neurodegeneration before the onset of dementia. If immune mediated processes are closely linked to neuronal breakdown it would be of importance to have a reliable means to detect these processes. Serum and cerebrospinal fluid (CSF) antibodies are discussed as such potential sources. The serendipitous use of the developing rat central nervous system (CNS) to screen CSF antibrain antibodies produced some unexpected findings. Firstly, CSF antibodies of AD and other dementia patients recognized distinctly different neuronal structures in the developing rat brain. Secondly, some AD CSF recognized fiber networks whereas others recognized amoeboid microglial cells. The same AD CSF which recognized amoeboid microglia cells also specifically marked activated microglia and neural macrophages in experimentally induced lesions. AD CSF microglial antibodies appear to be significant in view of the increasing association between microglia and neurogenerative processes in AD. In addition, CSF microglial antibodies are present in numerous at-risk descendants of familial AD patients. Some have subsequently developed the disorder. These findings together with the fact that microglial antibodies are usually found in the early stages of AD suggest that AD CSF microglial antibodies could be of value in detecting neurodegenerative processes before the onset of dementia. These findings add further support to the concept that inflammation and similar immune mechanisms may contribute to AD pathogenesis.