Sammendrag
Alzheimer’s disease (AD) is a neurodegenerative
disorder presenting one of the biggest
healthcare challenges in developed countries. No
effective treatment exists. In recent years the main
focus of AD research has been on the amyloid
hypothesis, which postulates that extracellular precipitates
of beta amyloid (Ab) derived from amyloid
precursor protein (APP) are responsible for the
cognitive impairment seen in AD. Treatment
strategies have been to reduce Ab production through
inhibition of enzymes responsible for its formation, or
to promote resolution of existing cerebral Ab plaques.
However, these approaches have failed to demonstrate
significant cognitive improvements. Intracellular
rather than extracellular events may be fundamental
in AD pathogenesis. Selenate is a potent inhibitor of
tau hyperphosphorylation, a critical step in the
formation of neurofibrillary tangles. Some selenium
(Se) compounds e.g. selenoprotein P also appear to
protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory
properties, and protect microtubules in the neuronal
cytoskeleton. Optimal function of these selenoenzymes
requires higher Se intake than what is common in
Europe and also higher intake than traditionally
recommended. Supplementary treatment with
N-acetylcysteine increases levels of the antioxidative
cofactor glutathione and can mediate adjuvant protection.
The present review discusses the role of Se in AD
treatment and suggests strategies for AD prevention by
optimizing selenium intake, in accordance with the
metal dysregulation hypothesis. This includes in particular
secondary prevention by selenium supplementation
to elderly with mild cognitive impairment.
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