Alternative Anti-Infective/Anti-Inflammatory Therapeutic Options for Fighting Alzheimer’s Disease
Pp. 1-153 (153)
Magda N. Tsolaki, Euphrosyni S. Koutsouraki, Georgios K. Katsipis, Pavlos Gr. Myserlis, Marilia A. Chatzithoma and Anastasia A. Pantazaki
Neurodegenerative diseases (NDs) have a serious impact on global health
with no effective treatments yet available. Alzheimer's disease (AD) is an incurable,
progressive neurodegenerative disorder, considered to be the most common cause of
dementia. There is increasing evidence for the infectious/inflammatory etiology of AD.
Although brain is assumed to be an immunologically isolated organ, many bacteria
(Helicobacter pylori), viruses (Herpes simplex virus, influenza, CMV etc.), fungi,
toxoplasma, are associated with AD. The presence of immune-related antigens around
amyloid plaques, activated complement factors, cytokines and a wide range of related
receptors in the brain of AD patients, led to the concept of “neuro-inflammation”.
Persistent or acute neuronal and peripheral inflammatory response to infectious agents
is gradually gaining more attention, as a risk factor for someone to develop sporadic
AD. The human microbiome (HM) has a pivotal role in nutrition, health and disease.
About 100 trillion bacteria from up to 1000 bacterial species inhabit the gastrointestinal
(GI) tract, contributing, at least in part, to what is known as the “human-biochemical”
or “genetic-individuality” and resistance to disease. Several pathologies, including AD
and inflammatory bowel disease, are associated with alterations in gut microbiome.
Microbes of the gut microbiota or of extracorporeal origin possess the ability of
producing functional amyloid proteins. These amyloids, via lymphatic and systemic
transport to the Central Nervous System (CNS), seem to have an important role in the
expression of neurologic and psychiatric disorders, such as schizophrenia, anxiety and
AD. Cross-seeding of the neurodegenerative disorder proteins may be induced by these
amyloids. Moreover, chronic inflammatory response to these immune-reactive proteins
can also be an important risk factor for CNS well-being. Therapeutic/preventive
options for halting CNS disorders’ onset, could include: (a) Anti-inflammatory, anti-amyloid drugs (β-sheet breakers and other inhibitors of amyloid fibrillization),
monoclonal antibodies, nanoparticles, which target pathological components of AD, or
other medical interventions to remove infectious agents or to ameliorate their
biochemical influence on GI-CNS tract, (b) Prebiotics to enhance the growth of desired
organisms and reduce oxidative stress - a cause that has been implicated with AD, (c)
Probiotics to provide both the desired bacteria, which increase the competitive effects
with pathogens, and essential metabolic products, and to modulate the host immune
system to resist in infection (d) The consumption of natural products, and the
dedication to the Mediterranean (MeDi) and Asian (AsDi) Diets, abundant in bioactive
compounds, are capable to prevent AD or reduce danger of AD, and strengthen the
host's ability to confront infections. The significance of diet diversity leading to the
microbiota diversity is a new clinically important concept. Finally, and (e) preventive
medical and/or other therapies to alter the amyloids produced by bacteria, to decrease
their production or stimulate their removal. This chapter is addressed to, and urges the
excellent cooperation between experts of neurology/psychiatry, microbiology,
biochemistry, dietary and nutritional sciences, in order to confront AD.
Alzheimer’s disease, Infection, Inflammation, Dietary interventions,
Natural products, Mediterranean Diet (MeDi), Asian Diet (AsDi), Anti-amyloid
treatment, Monoclonal antibodies, AD diagnosis, AD treatment.
Third Department of Neurology, Aristotle University, “G. Papanikolaou” Hospital, Thessaloniki, Greece.