Publication: Neurofibrillary pathology and
aluminum in Alzheimer's disease
Authors
Shin, R. W. ; Lee, V. M. Y ; Trojanowski, J. Q.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Since the first reports of aluminum-induced
neurofibrillary degeneration in experimental animals,
extensive studies have been performed to clarify the role
played by aluminum in the pathogenesis of Alzheimer's
disease (AD). Additional evidence implicating
aluminum in AD includes elevated levels of aluminum
in the AD brain, epidemiological data linking aluminum
exposure to AD, and interactions between aluminum and
protein components in the pathological lesions of AD,
¡.e., neurofibrillary tangles (NFTs) and senile plaques
(SPs). As most of this evidence is circumstantial and
some of it is not consistent in al1 reports, the role of
aluminum in the pathogenesis of AD has remained
controversial. However, the interaction of aluminum
with altered forms of t in the paired helical filaments
(PHFs) of neurofibrillary lesions is highly likely to
contribute to the formation of NFTs because (1)
aluminum and abnormally phosphorylated t (known as
PHFt) are colocalized in NFTs, and (2) aluminum is
known to preferentially interact with such phosphorylated
proteins. Recently, we demonstrated that
aluminum binds selectively to PHFt, induces PHFt to
aggregate, and retards the in vivo proteolysis of PHFt.
These data suggest that aluminum could serve as cofactor
in the formation of NFTs by interacting with
PHFt. This review summarizes current understanding of
how aluminum might contribute to the formation of
neurofibrillary lesions from PHFt in neurons of the AD
brain.
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