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Human brain myelination and amyloid beta deposition in Alzheimer's disease
Author(s) -
Bartzokis George,
Lu Po H.,
Mintz Jim
Publication year - 2007
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2007.01.019
Subject(s) - myelin , neuroscience , oligodendrocyte , amyloid beta , amyloid (mycology) , beta (programming language) , alzheimer's disease , in vivo , biology , pathology , chemistry , disease , medicine , central nervous system , genetics , computer science , programming language
We hypothesized that myelin breakdown in vulnerable late‐myelinating regions releases oligodendrocyte‐ and myelin‐associated iron that promotes amyloid beta (Aβ) oligomerization, its associated toxicity, and the deposition of oligomerized Aβ and iron in neuritic plaques observed in Alzheimer's disease (AD). The model was tested by using published maps of cortical myelination from 1901 and recent in vivo imaging maps of Aβ deposits in humans. The data show that in AD, radiolabeled ligands detect Aβ deposition in a distribution that matches the map of late‐myelinating regions. Furthermore, the strikingly lower ability of this imaging ligand to bind Aβ in animal models is consistent with the much lower levels of myelin and associated iron levels in rodents when compared with humans. The hypotheses derived from the “myelin model” are testable with current imaging methods and have important implications for therapeutic interventions that should be expanded to include novel targets such as oligodendrocytes, myelin, and brain iron.