The
amyloid hypothesis has so far been at the forefront of explaining the pathogenesis of
Alzheimer's Disease (AD), a progressive
neurodegenerative disorder that leads to
cognitive decline and eventual death. Recent evidence, however, points to additional factors that contribute to the pathogenesis of this disease. These include the neurovascular hypothesis, the mitochondrial cascade hypothesis, the inflammatory hypothesis, the
prion hypothesis, the mutational accumulation hypothesis, and the autoimmunity hypothesis. The purpose of this review was to briefly discuss the factors that are associated with autoimmunity in humans, including sex, the gut and lung microbiomes, age, genetics, and environmental factors. Subsequently, it was to examine the rise of autoimmune phenomena in AD, which can be instigated by a blood-brain barrier breakdown, pathogen
infections, and dysfunction of the glymphatic system. Lastly, it was to discuss the various ways by which immune system dysregulation leads to AD, immunomodulating
therapies, and future directions in the field of autoimmunity and neurodegeneration. A comprehensive account of the recent research done in the field was extracted from PubMed on 31 January 2022, with the keywords "
Alzheimer's disease" and "
autoantibodies" for the first search input, and "
Alzheimer's disease" with "
IgG" for the second. From the first search, 19 papers were selected, because they contained recent research on the
autoantibodies found in the biofluids of patients with AD. From the second search, four papers were selected. The analysis of the literature has led to support the autoimmune hypothesis in AD.
Autoantibodies were found in biofluids (serum/plasma, cerebrospinal fluid) of patients with AD with multiple methods, including ELISA, Mass Spectrometry, and microarray analysis. Through continuous research, the understanding of the synergistic effects of the various components that lead to AD will pave the way for better therapeutic methods and a deeper understanding of the disease.