Oligomerization of Alzheimer's β-Amyloid within Processes and Synapses of Cultured Neurons and Brain
Takahashi, Reisuke H. ; Almeida, Claudia G. ; Kearney, Patrick F. ; Yu, Fangmin ; Lin, Michael T. ; Milner, Teresa A. and Gouras, Gunnar K. LU
(2004)
In The Journal of Neuroscience
24(14).
p.3592-3599
- Abstract
Multiple lines of evidence implicate β-amyloid (Aβ) in the pathogenesis of Alzheimer's disease (AD), but the mechanisms whereby Aβ is involved remain unclear. Addition of Aβ to the extracellular space can be neurotoxic. Intraneuronal Aβ42 accumulation is also associated with neurodegeneration. We reported previously that in Tg2576 amyloid precursor protein mutant transgenic mice, brain Aβ42 localized by immunoelectron microscopy to, and accumulated with aging in, the outer membranes of multivesicular bodies, especially in neuronal processes and synaptic compartments. We now demonstrate that primary neurons from Tg2576 mice recapitulate the in vivo localization and accumulation of Aβ42 with time in culture. Furthermore, we demonstrate... (More)
Multiple lines of evidence implicate β-amyloid (Aβ) in the pathogenesis of Alzheimer's disease (AD), but the mechanisms whereby Aβ is involved remain unclear. Addition of Aβ to the extracellular space can be neurotoxic. Intraneuronal Aβ42 accumulation is also associated with neurodegeneration. We reported previously that in Tg2576 amyloid precursor protein mutant transgenic mice, brain Aβ42 localized by immunoelectron microscopy to, and accumulated with aging in, the outer membranes of multivesicular bodies, especially in neuronal processes and synaptic compartments. We now demonstrate that primary neurons from Tg2576 mice recapitulate the in vivo localization and accumulation of Aβ42 with time in culture. Furthermore, we demonstrate that Aβ42 aggregates into oligomers within endosomal vesicles and along microtubules of neuronal processes, both in Tg2576 neurons with time in culture and in Tg2576 and human AD brain. These Aβ42 oligomer accumulations are associated with pathological alterations within processes and synaptic compartments in Tg2576 mouse and human AD brains.
(Less)
- author
- Takahashi, Reisuke H.
; Almeida, Claudia G.
; Kearney, Patrick F.
; Yu, Fangmin
; Lin, Michael T.
; Milner, Teresa A.
and Gouras, Gunnar K.
LU
- publishing date
- 2004-04-07
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alzheimer, Amyloid, Oligomer, Pathology, Synapse, Transgenic
- in
- The Journal of Neuroscience
- volume
- 24
- issue
- 14
- pages
- 3592 - 3599
- publisher
- Society for Neuroscience
- external identifiers
-
- scopus:1842732209
- pmid:15071107
- ISSN
- 0270-6474
- DOI
- 10.1523/JNEUROSCI.5167-03.2004
- language
- English
- LU publication?
- no
- id
- 02bf96dc-5656-4e7d-bb1f-b0dce734b6be
- date added to LUP
- 2020-02-20 14:26:10
- date last changed
- 2024-05-30 12:14:39
@article{02bf96dc-5656-4e7d-bb1f-b0dce734b6be,
abstract = {{<p>Multiple lines of evidence implicate β-amyloid (Aβ) in the pathogenesis of Alzheimer's disease (AD), but the mechanisms whereby Aβ is involved remain unclear. Addition of Aβ to the extracellular space can be neurotoxic. Intraneuronal Aβ42 accumulation is also associated with neurodegeneration. We reported previously that in Tg2576 amyloid precursor protein mutant transgenic mice, brain Aβ42 localized by immunoelectron microscopy to, and accumulated with aging in, the outer membranes of multivesicular bodies, especially in neuronal processes and synaptic compartments. We now demonstrate that primary neurons from Tg2576 mice recapitulate the in vivo localization and accumulation of Aβ42 with time in culture. Furthermore, we demonstrate that Aβ42 aggregates into oligomers within endosomal vesicles and along microtubules of neuronal processes, both in Tg2576 neurons with time in culture and in Tg2576 and human AD brain. These Aβ42 oligomer accumulations are associated with pathological alterations within processes and synaptic compartments in Tg2576 mouse and human AD brains.</p>}},
author = {{Takahashi, Reisuke H. and Almeida, Claudia G. and Kearney, Patrick F. and Yu, Fangmin and Lin, Michael T. and Milner, Teresa A. and Gouras, Gunnar K.}},
issn = {{0270-6474}},
keywords = {{Alzheimer; Amyloid; Oligomer; Pathology; Synapse; Transgenic}},
language = {{eng}},
month = {{04}},
number = {{14}},
pages = {{3592--3599}},
publisher = {{Society for Neuroscience}},
series = {{The Journal of Neuroscience}},
title = {{Oligomerization of Alzheimer's β-Amyloid within Processes and Synapses of Cultured Neurons and Brain}},
url = {{http://dx.doi.org/10.1523/JNEUROSCI.5167-03.2004}},
doi = {{10.1523/JNEUROSCI.5167-03.2004}},
volume = {{24}},
year = {{2004}},
}