You are viewing a javascript disabled version of the site. Please enable Javascript for this site to function properly.
Go to headerGo to navigationGo to searchGo to contentsGo to footer
In content section. Select this link to jump to navigation

Myelin Basic Protein Associates with AβPP, Aβ1-42, and Amyloid Plaques in Cortex of Alzheimer's Disease Brain

Article type: Research Article

Authors: Zhan, Xinhuaa; * | Jickling, Glen C.a | Ander, Bradley P.a | Stamova, Boryanaa | Liu, DaZhia | Kao, Patricia F.b; c | Zelin, Mariko A.b; c | Jin, Lee-Wayb; c | DeCarli, Charlesa; b | Sharp, Frank R.a

Affiliations: [a] Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA | [b] Alzheimer's Disease Center, University of California at Davis, Sacramento, CA, USA | [c] Department of Pathology, University of California at Davis, Sacramento, CA, USA

Correspondence: [*] Correspondence to: Xinhua Zhan, MD, PhD, University of California at Davis, M.I.N.D. Institute – Room 2415, 2805 50th Street, Sacramento, CA 95817, USA. Tel.: +1 916 703 0449; Fax: +1 916 703 0369; E-mail: [email protected].

Keywords: Alzheimer's disease, amyloid-β, amyloid-β protein precursor, autophagy, axon damage, degraded myelin basic protein, myelin basic protein

DOI: 10.3233/JAD-142013

Journal: Journal of Alzheimer's Disease, vol. 44, no. 4, pp. 1213-1229, 2015

Accepted 17 October 2014
|
Published: 19 February 2015
Get PDF open access
Supplementary Materials:

Supplementary Table 1.

Supplementary Figure 1.

Supplementary Figure 2.

Abstract

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-β protein precursor (AβPP), and amyloid markers amyloid β1-42 (Aβ1-42) and FSB. Co-immunoprecipitation and mass spectroscopy evaluated interaction of AβPP/Aβ1-42 with MBP/dMBP. Evidence of axonal injury in AD cortex included appearance of AβPP 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 AβPP/Aβ1-42 with myelin or axonal components included (1) greater binding of dMBP with AβPP in AD brain; (2) MBP at the margins of amyloid plaques; (3) dMBP co-localized with Aβ1-42 in the core of amyloid plaques in AD brains; and (4) interactions between Aβ1-42 and MBP/dMBP by co-immunoprecipitation and mass spectrometry. We conclude that damaged axons may be a source of AβPP. dMBP, MBP, and NF associate with amyloid plaques and dMBP associates with AβPP and Aβ1-42. These molecules could be involved in formation of amyloid plaques.

Show more