Myelin Basic Protein Associates with A beta PP, A beta(1-42), and Amyloid Plaques in Cortex of Alzheimer's Disease Brain

摘要

The goal of this study was to show that myelin and axons in cortical gray matter are damaged in Alzheimer's disease (AD) brain. Superior temporal gyrus gray matter of AD patients (9 male, 14 female) was compared to cognitively normal controls (8 male, 7 female). Myelin basic protein (MBP) and a degraded myelin basic protein complex (dMBP) were quantified by Western blot. Brain sections were immunostained for MBP, dMBP, axonal neurofilament protein (NF), autophagy marker microtubule-associated proteins 1A/B light chain 3B precursor (LC3B), amyloid-beta protein precursor (A beta PP), and amyloid markers amyloid beta(1-42) (A beta(1-42)) and FSB. Co-immunoprecipitation and mass spectroscopy evaluated interaction of A beta PP/A beta(1-42) with MBP/dMBP. Evidence of axonal injury in AD cortex included appearance of A beta PP in NF stained axons, and NF at margins of amyloid plaques. Evidence of myelin injury in AD cortex included (1) increased dMBP in AD gray matter compared to control (p < 0.001); (2) dMBP in AD neurons; and (3) increased LC3B that co-localized with MBP. Evidence of interaction of A beta PP/A beta(1-42) with myelin or axonal components included (1) greater binding of dMBP with A beta PP in AD brain; (2) MBP at the margins of amyloid plaques; (3) dMBP co-localized with A beta(1-42) in the core of amyloid plaques in AD brains; and (4) interactions between A beta(1-42) and MBP/dMBP by co-immunoprecipitation and mass spectrometry. We conclude that damaged axons may be a source of A beta PP. dMBP, MBP, and NF associate with amyloid plaques and dMBP associates with A beta PP and A beta(1-42). These molecules could be involved in formation of amyloid plaques.