Does a pro-inflammatory process precede Alzheimer's disease and mild cognitive impairment?

Area of Science:

• Neuroscience
• Immunology
• Pathology

Background:

• Alzheimer's disease (AD) is characterized by plaque-dependent neuroinflammation, evident in human and animal models.
• The precise timing of neuroinflammation onset relative to plaque deposition in AD remains unclear.
• Inflammation may precede plaque formation in preclinical, asymptomatic AD stages.

Purpose of the Study:

• To review clinical and experimental evidence of neuroinflammation during preclinical AD.
• To explore factors initiating pre-plaque inflammation, focusing on soluble amyloid-beta (Aβ) oligomers.
• To analyze consequences of microglial activation and NGF metabolism deregulation in early AD pathology.

Main Methods:

• Review of existing clinical and experimental data from human specimens and transgenic AD models.
• Analysis of factors implicated in early, pre-plaque inflammatory processes.
• Examination of microglial activation and nerve growth factor (NGF) metabolism in early amyloid pathology.

Main Results:

• Evidence suggests pro-inflammatory processes may initiate before significant plaque deposition in AD.
• Soluble Aβ oligomers are highlighted as key factors in early, pre-plaque inflammation.
• Microglial activation and altered NGF metabolism are consequences of early amyloid pathology.

Conclusions:

• Neuroinflammation in Alzheimer's disease can occur in preclinical stages, prior to or independent of plaque formation.
• Soluble Aβ oligomers play a crucial role in initiating early inflammatory responses.
• Matrix metalloproteinase-9 (MMP-9) shows promise as a biomarker for detecting early central nervous system (CNS) inflammation in AD.