Myelin basic protein associates with AßPP, Aß1-42, and amyloid plaques in cortex of Alzheimer's disease brain.

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-ß protein precursor (AßPP), and amyloid markers amyloid ß1-42 (Aß1-42) and FSB. Co-immunoprecipitation and mass spectroscopy evaluated interaction of AßPP/Aß1-42 with MBP/dMBP. Evidence of axonal injury in AD cortex included appearance of AßPP 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 AßPP/Aß1-42 with myelin or axonal components included (1) greater binding of dMBP with AßPP in AD brain; (2) MBP at the margins of amyloid plaques; (3) dMBP co-localized with Aß1-42 in the core of amyloid plaques in AD brains; and (4) interactions between Aß1-42 and MBP/dMBP by co-immunoprecipitation and mass spectrometry. We conclude that damaged axons may be a source of AßPP. dMBP, MBP, and NF associate with amyloid plaques and dMBP associates with AßPP and Aß1-42. These molecules could be involved in formation of amyloid plaques.