Record: found
Abstract: found
Article: not found

Intracellular amyloid-beta in Alzheimer's disease.

Author(s): Lawrence W. Green, Salvatore Oddo, Kim N. Green, Frank LaFerla

Publication date: 2007-06-30

Keywords: Alzheimer Disease, genetics, metabolism, physiopathology, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Animals, Brain, pathology, Extracellular Fluid, Humans, Intracellular Fluid, Plaque, Amyloid, Proteasome Endopeptidase Complex, Synaptic Transmission, physiology

Read this article at

ScienceOpenPublisher PubMed

Bookmark

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

The primal role that the amyloid-beta (Abeta) peptide has in the development of Alzheimer's disease is now almost universally accepted. It is also well recognized that Abeta exists in multiple assembly states, which have different physiological or pathophysiological effects. Although the classical view is that Abeta is deposited extracellularly, emerging evidence from transgenic mice and human patients indicates that this peptide can also accumulate intraneuronally, which may contribute to disease progression.

Related collections

Most cited references 4

Record: found
Abstract: found
Article: not found

Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology.

Reisuke H. Takahashi, Teresa A Milner, Feng Li … (2002)

A central question in Alzheimer's disease concerns the mechanism by which beta-amyloid contributes to neuropathology, and in particular whether intracellular versus extracellular beta-amyloid plays a critical role. Alzheimer transgenic mouse studies demonstrate brain dysfunction, as beta-amyloid levels rise, months before the appearance of beta-amyloid plaques. We have now used immunoelectron microscopy to determine the subcellular site of neuronal beta-amyloid in normal and Alzheimer brains, and in brains from Alzheimer transgenic mice. We report that beta-amyloid 42 localized predominantly to multivesicular bodies of neurons in normal mouse, rat, and human brain. In transgenic mice and human Alzheimer brain, intraneuronal beta-amyloid 42 increased with aging and beta-amyloid 42 accumulated in multivesicular bodies within presynaptic and especially postsynaptic compartments. This accumulation was associated with abnormal synaptic morphology, before beta-amyloid plaque pathology, suggesting that intracellular accumulation of beta-amyloid plays a crucial role in Alzheimer's disease.