Intraneuronal Alzheimer Aβ42 accumulates in multivesicular bodies and is associated with synaptic pathology
Takahashi, Reisuke H. ; Milner, Teresa A. ; Li, Feng ; Nam, Ellen E. ; Edgar, Mark A. ; Yamaguchi, Haruyasu ; Beal, M. Flint ; Xu, Huaxi ; Greengard, Paul and Gouras, Gunnar K. LU
(2002)
In American Journal of Pathology
161(5).
p.1869-1879
- Abstract
A central question in Alzheimer's disease concerns the mechanism by which β-amyloid contributes to neuropathology, and in particular whether intracellular versus extracellular β-amyloid plays a critical role. Alzheimer transgenic mouse studies demonstrate brain dysfunction, as β-amyloid levels rise, months before the appearance of β-amyloid plaques. We have now used immunoelectron microscopy to determine the subcellular site of neuronal β-amyloid in normal and Alzheimer brains, and in brains from Alzheimer transgenic mice. We report that β-amyloid 42 localized predominantly to multivesicular bodies of neurons in normal mouse, rat, and human brain. In transgenic mice and human Alzheimer brain, intraneuronal β-amyloid 42 increased with... (More)
A central question in Alzheimer's disease concerns the mechanism by which β-amyloid contributes to neuropathology, and in particular whether intracellular versus extracellular β-amyloid plays a critical role. Alzheimer transgenic mouse studies demonstrate brain dysfunction, as β-amyloid levels rise, months before the appearance of β-amyloid plaques. We have now used immunoelectron microscopy to determine the subcellular site of neuronal β-amyloid in normal and Alzheimer brains, and in brains from Alzheimer transgenic mice. We report that β-amyloid 42 localized predominantly to multivesicular bodies of neurons in normal mouse, rat, and human brain. In transgenic mice and human Alzheimer brain, intraneuronal β-amyloid 42 increased with aging and β-amyloid 42 accumulated in multivesicular bodies within presynaptic and especially postsynaptic compartments. This accumulation was associated with abnormal synaptic morphology, before β-amyloid plaque pathology, suggesting that intracellular accumulation of β-amyloid plays a crucial role in Alzheimer's disease.
(Less)
- author
- Takahashi, Reisuke H.
; Milner, Teresa A.
; Li, Feng
; Nam, Ellen E.
; Edgar, Mark A.
; Yamaguchi, Haruyasu
; Beal, M. Flint
; Xu, Huaxi
; Greengard, Paul
and Gouras, Gunnar K.
LU
- publishing date
- 2002-11
- type
- Contribution to journal
- publication status
- published
- subject
- in
- American Journal of Pathology
- volume
- 161
- issue
- 5
- pages
- 1869 - 1879
- publisher
- American Society for Investigative Pathology
- external identifiers
-
- scopus:0036827031
- pmid:12414533
- ISSN
- 0002-9440
- DOI
- 10.1016/S0002-9440(10)64463-X
- language
- English
- LU publication?
- no
- id
- e4793489-929f-4f6d-8413-69301f1b84ba
- date added to LUP
- 2020-02-20 14:27:16
- date last changed
- 2024-04-17 05:47:05
@article{e4793489-929f-4f6d-8413-69301f1b84ba,
abstract = {{<p>A central question in Alzheimer's disease concerns the mechanism by which β-amyloid contributes to neuropathology, and in particular whether intracellular versus extracellular β-amyloid plays a critical role. Alzheimer transgenic mouse studies demonstrate brain dysfunction, as β-amyloid levels rise, months before the appearance of β-amyloid plaques. We have now used immunoelectron microscopy to determine the subcellular site of neuronal β-amyloid in normal and Alzheimer brains, and in brains from Alzheimer transgenic mice. We report that β-amyloid 42 localized predominantly to multivesicular bodies of neurons in normal mouse, rat, and human brain. In transgenic mice and human Alzheimer brain, intraneuronal β-amyloid 42 increased with aging and β-amyloid 42 accumulated in multivesicular bodies within presynaptic and especially postsynaptic compartments. This accumulation was associated with abnormal synaptic morphology, before β-amyloid plaque pathology, suggesting that intracellular accumulation of β-amyloid plays a crucial role in Alzheimer's disease.</p>}},
author = {{Takahashi, Reisuke H. and Milner, Teresa A. and Li, Feng and Nam, Ellen E. and Edgar, Mark A. and Yamaguchi, Haruyasu and Beal, M. Flint and Xu, Huaxi and Greengard, Paul and Gouras, Gunnar K.}},
issn = {{0002-9440}},
language = {{eng}},
number = {{5}},
pages = {{1869--1879}},
publisher = {{American Society for Investigative Pathology}},
series = {{American Journal of Pathology}},
title = {{Intraneuronal Alzheimer Aβ42 accumulates in multivesicular bodies and is associated with synaptic pathology}},
url = {{http://dx.doi.org/10.1016/S0002-9440(10)64463-X}},
doi = {{10.1016/S0002-9440(10)64463-X}},
volume = {{161}},
year = {{2002}},
}