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. 2011 Jan;1(1):292-6.
doi: 10.1159/000329544. Epub 2011 Sep 20.

Lipofuscin Hypothesis of Alzheimer's Disease

Free PMC article

Lipofuscin Hypothesis of Alzheimer's Disease

Giorgio Giaccone et al. Dement Geriatr Cogn Dis Extra. .
Free PMC article


The primary culprit responsible for Alzheimer's disease (AD) remains unknown. Aβ protein has been identified as the main component of amyloid of senile plaques, the hallmark lesion of AD, but it is not definitively established whether the formation of extracellular Aβ deposits is the absolute harbinger of the series of pathological events that hit the brain in the course of sporadic AD. The aim of this paper is to draw attention to a relatively overlooked age-related product, lipofuscin, and advance the hypothesis that its release into the extracellular space following the death of neurons may substantially contribute to the formation of senile plaques. The presence of intraneuronal Aβ, similarities between AD and age-related macular degeneration, and the possible explanation of some of the unknown issues in AD suggest that this hypothesis should not be discarded out of hand.

Keywords: Alzheimer's disease; Amyloid; Aβ protein; Lipofuscin; Macular degeneration; Neurofibrillary tangles.

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