Neuroinflammation in Preclinical Alzheimer's Disease: A Review of Current Evidence

The pathology of sporadic Alzheimer’s disease (AD) may be present at mid-life and precede the prodromal and clinical dementia syndromes associated with the disorder by decades. Few successful therapeutic treatments exist and, as a result, attention is turning to the preclinical stages of the disease for the development of future intervention strategies. The success of such strategies will rely on well-defined biomarkers of preclinical disease to identify and monitor changes earlier in the disease course. Here, we consider whether immune function changes are potentially useful markers of preclinical disease. We have selected studies spanning epidemiological, animal, clinical and imaging research pertaining to the earliest stages of AD pathogenesis, as well as studies of non-demented adults at high AD risk. We examine changes in inflammatory markers, alongside changes in established biomarkers, to highlight their suitability as disease indicators across preclinical and prodromal stages. We conclude that further work surrounding this topic is required, calling for larger prospective epidemiological studies of preclinical disease that incorporate serial assessment designs with a wider range of inflammatory mediators. We anticipate that future benefits of work in this area include improved disease detection and modification, as well as diagnostic accuracy of trial participants, leading to more cost-effective observation and intervention studies.