Autotoxicity and Alzheimer disease.

Area of Science:

• Neuroimmunology
• Pathology
• Immunology

Background:

• Traditional immunological responses include humoral (B lymphocytes) and cell-mediated (T lymphocytes) immunity, leading to autoimmune diseases.
• Inflammation is a non-specific response to injury, characterized by serum exudation and cardinal signs like redness and swelling.
• Classic immunological and inflammatory models do not fully explain pathological observations in Alzheimer disease (AD) brain tissue.

Purpose of the Study:

• To re-evaluate the nature of the immune response observed in Alzheimer disease brain tissue.
• To clarify the role of the innate immune system in neurodegenerative diseases.
• To explore the immunological privilege of the brain.

Main Methods:

• Pathological examination of Alzheimer disease-affected brain tissue.
• Comparison of observed pathological features with classic immunological and inflammatory responses.
• Analysis of the presence and absence of immune cells (B lymphocytes, T cells) and proteins in AD lesions.

Main Results:

• Alzheimer disease lesions show components of peripheral immunological and inflammatory states but lack identifiable B lymphocytes and antibodies, with sparse T cells.
• The blood-brain barrier remains intact, preventing serum protein exudation.
• The observed reaction in AD is best defined as an innate immunoreaction, distinct from classic inflammation or autoimmunity.

Conclusions:

• The immune response in Alzheimer disease is an innate immunoreaction, not a typical inflammatory or autoimmune process.
• The brain's capacity to mount an innate immunoreaction challenges the concept of immunological privilege.
• Further research is needed to understand the innate immune system's operation in health and disease, particularly at the tissue level.