The Immune System and Neuroinflammation as Potential Sources of Blood-Based Biomarkers for Alzheimer’s Disease, Parkinson’s Disease, and Huntington’s Disease

Abstract

Neurodegenerative diseases are characterized by a loss of neurons that leads to cognitive and behavioral dysfunction. Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting millions of people in the United States and worldwide, followed by Parkinson's disease (PD). While some early onset forms of AD and PD are hereditary, the sporadic or late-onset cases are believed to result from lifestyle and environmental factors. On the contrary, Huntington's disease (HD) is a neurodegenerative disease solely caused by mutations in the gene for huntingtin protein. The disease mechanisms at play for all three disorders remain elusive, hampering efforts to develop effective therapeutic interventions. In light of this, the discovery of robust biomarkers is crucial in order to identify people at risk for AD and PD, preferably before symptoms arise. For all three diseases, the identification of biomarkers would not only allow development of treatments but also evaluation and adjustment of these with disease progression. It is now understood that neuroinflammation plays a crucial role in neurodegenerative diseases, along with subsequent immune activation. Therefore, research is actively ongoing to discover and evaluate inflammatory and immune-related biomarkers. Recent progress in this area for AD, PD, and HD is presented here.

Leukocyte telomere shortening in Huntington's disease

“…There is evidence that toxic HTT aggregates are accompanied by a neuroinflammatory state characterized by activation of the microglia in the brain of HD patients [31][32][33]. Microglia activation can be observed early in pre-manifest HD, followed by the release of proinflammatory mediators.…”

The Exceptional Vulnerability of Humans to Alzheimer’s Disease

“…Myriad genetic polymorphisms appear to influence the odds of developing AD [105], but (except for the APOE type, above) the impact of individual genetic variants is small. In addition, such factors as epigenetics [106], inflammation/immune activation [107], proteostasis [108], or posttranslational modifications of proteins such as glycosylation [109] have been linked to the risk for AD in humans, as have metabolic and cardiovascular disorders [110]. Other factors that can vary within and among species should not be overlooked, such as life-long activity levels [111], sleep patterns [112], head injury [113], psychosocial stress [114], diet [115], microbiome [116–118], and environmental exposure to microorganisms and viruses [119].…”

Marijuana Compounds: A Nonconventional Approach to Parkinson’s Disease Therapy

“…Inflammation has been shown to be a crucial pathological factor responsible for the demise of dopaminergic neurons in PD [234–236]. Glial cells appear to play a key role in neuroinflammation, since higher levels of activated microglia are reported in the substantia nigra of patients with PD compared to brains of control subjects [237, 238].…”