The potential of circulating autoantibodies in the early diagnosis of Alzheimer’s disease

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder frequently diagnosed among the aged suffering with cognitive loss. Managing the disease has considerable economic impact on society. AD is characterized by the presence of amyloid plaque and neurofibrillary tangles, which accompany neuronal loss. There is currently no routine blood test to help to diagnose the disease. Direct tracking of AD-related molecules is difficult and costly because they are confined to the central nervous system. However, in early stage AD patients, some autoantibodies can cross the blood brain barrier to build the bridge from internal brain molecules to blood by crossing the blood brain barrier. Recent studies showed that autoantibodies which target AD-related molecules change quantitatively in the periphery along with AD pathology. More importantly, autoantibodies with different targets show diverse features in different stages of AD and in other similar kinds of dementias. This review introduces four main AD-related autoantibodies recognizing separately, amyloid-β precursor proteins, τ protein, S100b and phospholipid. While there is limited specificity and sensitivity for a single autoantibody biomarker for AD diagnosis, a combination analysis using several autoantibodies and traditional clinical diagnostics at the same time can be a promising topic for prospective research into early stage AD diagnosis.